BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous condition with variable outcomes. The prognostic value of common clinical risk factors for major adverse cardiac events (MACEs) and all-cause mortality remains unclear. This study systematically evaluates associations between traditional risk factors and adverse outcomes in MINOCA. METHODS: A systematic review and meta-analysis was conducted to assess pooled hazard ratios (HRs) for clinical variables associated with MACEs and all-cause mortality. Eligible studies reporting HRs with at least 6 months of follow-up were included. Random-effects models were used to derive pooled estimates. RESULTS: Eleven studies including 12,081 patients were analyzed. Over a mean follow-up of 49.2 months, pooled MACEs incidence was 17% (95% CI: 11-26%) and all-cause mortality was 10% (95% CI: 8-14%). Older age increased the risk of MACEs (HR: 1.02; 95% CI: 1.01-1.04), while higher BMI was protective (HR: 0.92; 95% CI: 0.86-0.99). For all-cause mortality, significant predictors included age (HR: 1.04 per year), diabetes (HR: 1.33; 95% CI: 1.07-1.64), creatinine (HR: 1.01; 95% CI: 1.0009-1.02), and STEMI-pattern presentation (HR: 2.85; 95% CI: 1.09-7.44). Higher BMI (HR: 0.89; 95% CI: 0.82-0.98) and dyslipidemia (HR: 0.83; 95% CI: 0.76-0.90) were associated with lower mortality. CONCLUSION: Only select clinical variables predict outcomes in MINOCA, while many traditional MI risk factors do not. These findings highlight the need for MINOCA-specific risk models and targeted management strategies.

BACKGROUND: Ultrasound (US)-guided axillary vein puncture (AVP) is an established technique for cardiac implantable electronic device (CIED) implantation. Yet real-world data concerning shifting from conventional venous access into US-guided AVP are not widely available. METHODS: This is a single-center prospective registry reporting safety (complications) and efficacy (success rate: i.e., accomplishment of the vein access utilizing only the initially employed approach) of self-taught US-guided AVP integration into the standard workflow of CIED procedures. RESULTS: A total of 539 patients (mean age 71.5 ± 12.4 years old, 78.7% males) were treated in our institution over a three-year period. Regarding CIED type and lead number, 58.3% used an implantable cardioverter defibrillator, 32% used permanent pacemakers, and two leads were involved in 65.8% of the cases and three leads in 8.9%. Before integration of US-guided AVP, the venous access success rate was 93.5%. The US-guided AVP success rate was 377/400 procedures (94.2%). After the first semester of US-guided AVP utilization, a pattern of increased success rate was observed ( = 0.002) and remained stable over the following semesters. No major complication (periprocedural or 30-day mortality, hemothorax, pneumothorax and tamponade) occurred after US AVP integration in our workflow. CONCLUSIONS: The integration of US-guided AVP in a self-taught manner is feasible among electrophysiologists with experience in US-guided vascular access. A high success rate can be reached quickly and safely.

: The triglyceride-glucose (TyG) index is an accessible surrogate marker of insulin resistance and has been increasingly investigated for its prognostic relevance in cardiovascular disease. However, evidence regarding its predictive value for major adverse cardiovascular events (MACEs) in patients with acute coronary syndromes (ACSs) remains inconsistent. This study systematically assessed the association between TyG index and the risk of MACEs in individuals with ACS. : Following PRISMA 2020 guidelines, PubMed, ScienceDirect, and ClinicalTrials.gov were searched through October 2025. Ten observational cohort studies including 32,751 ACS patients were analyzed. Studies reporting fully adjusted hazard ratios (HRs) for the association between TyG index and MACEs were eligible. A random-effects model was used to pool effect sizes expressed as adjusted HRs per 1-unit increase in the TyG index. Heterogeneity, sensitivity analyses, publication bias assessment, and meta-regression were conducted. : Higher TyG index values were significantly associated with increased MACE risk (pooled adjusted HR 1.45, 95% CI 1.25-1.68, I = 80%). Leave-one-out analysis confirmed robustness. Meta-regression analysis suggested a stronger association in cohorts consisting exclusively of patients with type 2 diabetes mellitus, with a trend toward larger effect estimates in smaller studies, potentially contributing to the observed heterogeneity. Despite small-study effects, trim-and-fill-adjusted estimates remained significant (HR 1.26, 95% CI 1.05-1.52). : An elevated TyG index is independently associated with higher MACE risk in ACS patients and may be considered as an additive metabolic risk marker in combination with established risk stratification tools, pending further prospective validation.

BACKGROUND: Electrical storm (ES) is a life- threatening condition. Both recurrence and mortality rates remain unacceptably high. Current guidelines recommend initial conservative approach using anti-arrhythmic drugs (AADs), followed by catheter ablation (CA) for those with refractory ES. METHODS: We searched PubMed and Scopus for articles comparing an initial conservative approach - based on AADs/ sedation- with an early referral for CA approach. The primary endpoint was long term mortality, while secondary endpoints included ES recurrence and the incidence of ventricular arrhythmias (VAs)/ defibrillator shocks during the follow- up. RESULTS: Seven studies, primarily observational cohorts, were analyzed. The pooled population (999 patients) consisted mostly of males with ischemic cardiomyopathy, presenting with ventricular tachycardias (VTs). The mean left ventricular ejection fraction was 35.5 % (9.5 %). 493 patients were treated with CA during the index hospitalization. Early CA was associated with significantly lower long- term mortality (OR: 0.44, 95 %CI: 0.31-0.63). Additionally, it was associated with lower rates of both ES recurrence and VAs/ shocks during the follow- up (OR: 0.27, 95 %CI: 0.15-0.48 and OR: 0.33, 95 %CI: 0.21-0.52, respectively). CONCLUSIONS: Meta- analysis of primarily observational studies revealed that early referral of ES patients for CA may improve their prognosis. The invasive approach was associated with lower mortality and reduced recurrence rates of major arrhythmic events. Although some inherent limitations affect the strength of these findings, they remain promising. They highlight the need for further research on the topic, as their confirmation in randomized trials could lead to a shift in the standard of care of ES patients.

BACKGROUND: Atrial fibrillation (AF) is the most common supraventricular arrhythmia and is associated with an impaired prognosis. Studies using implantable cardiac monitors suggest that this association is closely linked to AF burden, defined as the percentage of time spent in AF. Consequently, there is a growing need for affordable and comfortable alternative devices, such as wearables, capable of reliably monitoring AF burden in patients with AF. METHODS: Major electronic databases were searched for studies comparing AF burden quantification using wearables and reference ECG monitoring methods. A Bayesian approach was adopted for the final analysis. RESULTS: Six studies, including a total of 448 patients and 36,978 h of valid simultaneous recordings, were analyzed. Bayesian analysis revealed no statistically significant differences between wearables and reference methods in AF burden quantification. The mean error was 1% (95% CrIs: -4% to 7%). Similar findings were observed in the subgroup analysis of studies assessing only smartwatches. Between-study heterogeneity was low, and no evidence of publication bias was detected. CONCLUSION: Our analysis suggests that AF burden quantification using wearables is comparable to reference ECG monitoring methods. These findings support the potential role of wearables in clinical practice, particularly for research and prognostic purposes. However, more studies are needed to determine whether the observed statistical equivalence translates to clinical significance, thereby supporting the widespread use of wearables in the assessment of rhythm control therapeutic strategies.

Obesity is an important risk factor for atrial fibrillation (AF) development. Data on cryoballoon ablation (CBA) outcomes in obese patients have so far been scarce. We reviewed the existing literature to compare the efficacy and safety of CBA in obese versus non-obese AF patients. A systematic literature search was conducted for studies comparing clinical outcomes (arrhythmia recurrence and/or procedural data and/or safety outcomes) between obese and non-obese patients undergoing CBA for AF. Statistical pooling was performed according to a random-effects model with generic inverse-variance weighting of relative risks (RRs) and standardised mean differences (SMDs) computing risk estimates with 95% confidence intervals (CIs). Obese and non-obese patients had comparable arrhythmia recurrence rates (normal versus overweight, RR = 0.95, 95% CI: 0.82-1.11, = 0.55, I% = 91%; normal versus class I obesity, RR = 0.97, 95% CI: 0.82-1.13, = 0.68, I% = 87%; normal versus class II obesity, RR = 0.98, 95% CI: 0.91-1.07, = 0.29, I% = 65%). Procedure time was marginally increased in obese patients compared to non-obese counterparts (normal versus overweight, SMD = 0.05, 95% CI: -0.15-0.26, = 0.62, I% = 74%; normal versus class I obesity, SMD = 0.10, 95% CI: -0.00-0.19, = 0.06, I% = 2%; overweight versus class I obesity, SMD = 0.11, 95% CI: 0.01-0.21, = 0.048, I% = 25%). Regarding radiation exposure, fluoroscopy time was increased in patients with class I obesity compared to normal-weight or overweight patients and dose area product was also increased in obese patients compared to non-obese patients. Lastly, the risk of complications did not differ between obese and non-obese patients. Statistical heterogeneity and the small number of patients included are the main limitations of this study. CBA seems to be effective for obese patients suffering from AF, featuring also similar safety outcomes with non-obese individuals. Radiation exposure was increased in obese patients.

BACKGROUND: Atrial fibrillation (AF) is prevalent among obese patients, and cryoballoon ablation (CBA) is an effective strategy for the rhythm control of AF. The impact of body mass index (BMI) on the clinical outcomes of CBA for AF is not fully explored. METHODS: 85 consecutive patients with paroxysmal AF were enrolled and were categorized into three groups as per their BMI: normal weight (BMI 18.5-25 kg/m), overweight (BMI 25-30 kg/m), and obese patients (BMI > 30 kg/m). The primary study endpoint was a late (12 month) recurrence of AF. Early recurrence of AF, symptom improvement, and procedural outcomes were some key secondary outcomes. RESULTS: 20 patients had normal weight, 35 were overweight, and 30 were obese. Obese patients featured a higher prevalence of diabetes mellitus, heavier exposure to smoking, and worse baseline symptoms (as assessed through EHRA class at admission and 12 months before CBA) compared to overweight and normal weight patients. Both late and early (<3 months) AF recurrence rates were comparable across the three groups. Of note, obese patients showed greater improvement in their symptoms post-CBA, defined as improvement by at least one EHRA class, compared to normal weight patients; this might be explained by improved diastolic function. Total procedure time and dose area product were significantly increased in obese patients. The multivariate logistic regression analysis indicated that early AF recurrence and the duration of hypertension are independent predictors of late AF recurrence. CONCLUSION: CBA is effective in overweight and obese patients with paroxysmal AF. Procedure time and radiation exposure are increased in obese patients undergoing CBA.

BACKGROUND: Atrial fibrillation (AF) is the commonest supraventricular arrhythmia in adults. Timely AF diagnosis seems to ameliorate patients prognosis. PURPOSE: To investigate the association between peak left atrial longitudinal strain (PALS) and new onset AF in the general population. OBJECTIVES: We searched major electronic databases for articles assessing the relationship between PALS and incident AF. RESULTS: Eight studies (11,145 patients) were analysed. Lower levels of PALS were significantly associated with higher risk of incident AF (HR: 0.95; 95%CI: 0.92-0.97, : 83%). According to the diagnostic accuracy meta-analysis, PALS <33.4% presents 64% (95%CI: 46-79%) sensitivity and 69% (95%CI: 63-75%) specificity. CONCLUSIONS: In a relatively healthy population, lower levels of PALS were significantly associated with incident AF. The overall diagnostic accuracy was moderate. Lower levels of PALS seem to justify an opportunistic - rather than a systematic-screening approach. These findings could allow more efficient utilisation of healthcare resources.

BACKGROUND: Cryptogenic stroke (CS) remains a significant cause of morbidity. Failure to identify the underlying pathology increases the rate of recurrence. Atrial fibrillation (AF) seems to be responsible for a substantial proportion of CS. Thus, there is an unmet need to identify and properly treat those with silent AF. PURPOSE: To investigate the association between left atrial strain and newly diagnosed AF in CS patients. OBJECTIVES: We searched major electronic databases for articles assessing the relationship between either peak left atrial longitudinal (PALS) or peak contractile (PACS) strain-quantified using speckle tracking echocardiography-and the incidence of occult AF during the diagnostic work-up of CS patients. RESULTS: Eleven studies (two thousand and eighty-one patients) were analyzed. Incidence of occult AF was 19%. Both PALS and PACS were significantly lower in patients with newly diagnosed AF (MD - 8.6%, 95%CI - 10.7 to - 6.4, I 86.4% and MD - 5.5, 95%CI - 6.8 to - 4.2, I 80.8%). According to the diagnostic accuracy meta-analysis, PALS < 20% present 71% (95%CI 47-87%) sensitivity and 71% (95%CI 60-81%) specificity for the diagnosis of occult AF, assuming a prevalence of 20%. The corresponding values for PACS < 11% are 83% (95%CI 57-94%) and 78% (95%CI 56-91%). CONCLUSION: Both PALS and PACS are significantly lower in patients with CS and silent AF. It seems that the cut-off values mentioned above could help physicians in identifying patients who may benefit more from prolonged rhythm monitoring. More studies are needed to confirm these findings.

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?

Inflammation, as assessed by epicardial adipose tissue and serum biomarkers, represents an integral mechanistic link in isolated coronary artery ectasia (iCAE) pathogenesis. This should be further investigated in the context of iCAE management and risk stratification.

BACKGROUND: For years, physical activity (PA) has been considered a mixed blessing in terms of the risk of incident atrial fibrillation (AF). Previous analyses have had equivocal results regarding the cut-off of PA level beyond which AF risk increases, if such a limit really does exist. Data regarding females in particular have been scarce. METHODS: We performed a dose-response meta-analysis to investigate the relationship between weekly PA and the risk for AF in females. Major electronic databases were searched for studies assessing the association between leisure time PA and the risk for incident AF in females from the general population. The linearity of the dose-response curve was assessed using the restricted cubic spline model. RESULTS: A total of 15 studies, which involved 1,821,422 females, were included in the final analysis. AF incidence was 3.7%. Dose-response analysis revealed an inverse nonlinear relationship between weekly PA and the risk for incident AF (p for linearity <0.0001). No significant heterogeneity was documented (I = 37%). Cautious interpretation is needed for PA exceeding 50 metabolic equivalents of task- hours per week (METs- h/w), due to limited available data for these high levels of PA. CONCLUSION: According to this analysis, physicians can safely advise females to perform up to 50METs- h/w of moderate or vigorous PA, to reduce the risk for future AF. Interestingly, significant benefit can be attained even at low levels of regular weekly PA.

BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA). METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices. RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = - 0.66; 95% CI (- 1.01, - 0.32) and SMD = - 0.56; 95% CI (- 0.73, - 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis. CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.

Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

(1)Introduction: Catheter ablation has become a cornerstone for the management of patients with atrial fibrillation (AF). Nevertheless, recurrence rates remain high. Epicardial adipose tissue (EAT) has been associated with AF pathogenesis and maintenance. However, the literature has provided equivocal results regarding the relationship between EAT and post-ablation recurrence.(2) Purpose: to investigate the relationship between total and peri-left atrium (peri-LA) EAT with post-ablation AF recurrence. (3) Methods: major electronic databases were searched for articles assessing the relationship between EAT, quantified using computed tomography, and the recurrence of AF following catheter ablation procedures. (4) Results: Twelve studies (2179 patients) assessed total EAT and another twelve (2879 patients) peri-LA EAT. Almost 60% of the included patients had paroxysmal AF and recurrence was documented in 34%. Those who maintained sinus rhythm had a significantly lower volume of peri-LA EAT (SMD: -0.37, 95%; CI: -0.58-0.16, I2: 68%). On the contrary, no significant difference was documented for total EAT (SMD: -0.32, 95%; CI: -0.65-0.01; I2: 92%). No differences were revealed between radiofrequency and cryoenergy pulmonary venous isolation. No publication bias was identified. (5) Conclusions: Only peri-LA EAT seems to be predictive of post-ablation AF recurrence. These findings may reflect different pathophysiological roles of EAT depending on its location. Whether peri-LA EAT can be used as a predictor and target to prevent recurrence is a matter of further research.

BACKGROUND: The wearable cardioverter defibrillator (WCD), (LifeVest, ZOLL, Pittsburgh, PA, USA) is a medical device designed for the temporary detection and treatment of malignant ventricular tachyarrhythmias. WCD telemonitoring features enable the evaluation of the physical activity (PhA) of the patients. We sought to assess with the WCD the PhA of patients with newly diagnosed heart failure. METHODS: We collected and analyzed the data of all patients treated with the WCD in our clinic. Patients with newly diagnosed ischemic, or non-ischemic cardiomyopathy and severely reduced ejection fraction, who were treated with the WCD for at least 28 consecutive days and had a compliance of at least 18 h the day were included. RESULTS: Seventy-seven patients were eligible for analysis. Thirty-seven patients suffered from ischemic and 40 from non-ischemic heart disease. The average days the WCD was carried was 77.3 ± 44.6 days and the mean wearing time was 22.8 ± 2.1 h. The patients showed significantly increased PhA measured by daily steps between the first two and the last two weeks (Mean steps in the first 2 weeks: 4,952.6 ± 3,052.7 vs. mean steps in the last 2 weeks: 6,119.6 ± 3,776.2, -value:  < 0.001). In the end of the surveillance period an increase of the ejection fraction was observed (LVEF-before: 25.8 ± 6.6% vs. LVEF-after: 37.5 ± 10.6%,  < 0.001). Improvement of the EF did not correlate with the improvement of PhA. CONCLUSION: The WCD provides useful information regarding patient PhA and may be additionally utilized for early heart failure treatment adjustment.

Buffle et al are to be congratulated for shedding more light on the electrophysiologic links regarding atrial fibrillation recurrence post radiofrequency catheter ablation. The different approaches of left atrium volume and left atrium diameter assessment employed in this study, is a limitation that should not go unnoticed, since angiographically calculated left atrium volume overestimates volume as compared to 3D echo measurements. Further, the timing of change has been reported to have prognostic significance; namely left atrium diameter reduction within the 3 month blanking period has been reported to independently predict prolonged arrhythmia free survival. Hence, we firmly believe that future studies should examine any potential correlations between left atrium diameter and recurrence mechanisms.

INTRODUCTION: Early arrhythmia recurrence within the 3-month blanking period is a common event that historically has been attributed to reversible phenomena. While its mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation. METHODS: The MEDLINE database, ClinicalTrials. gov, medRxiv, and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for atrial fibrillation. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence. RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (odds ratio [OR]: 5.31; 95% confidence interval [CI]: 3.75-7.51). This pattern remained unchanged after subanalyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting antiarrhythmic drug utilization during the blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity. CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier reintervention is an open research avenue.

OBJECTIVES: Many of the complications arising from cardiac device implantation are associated to the venous access used for lead placement. Previous analyses reported that cephalic vein cutdown (CVC) is safer but less effective than subclavian vein puncture (SVP). However, comparisons between these techniques and axillary vein puncture (AVP) - guided either by ultrasound or fluoroscopy - are lacking. Thus, we aimed to compare safety and efficacy of these approaches. METHODS: We searched for articles assessing at least two different approaches regarding the incidence of pneumothorax and/or lead failure (LF). When available, bleeding and infectious complications as well as procedural success were analyzed. A frequentist random effects network meta-analysis model was adopted. RESULTS: Thirty-six studies were analyzed. Most articles assessed SVP versus CVC. Compared to SVP, both CVC and AVP were associated with reduced odds of pneumothorax (OR: 0.193, 95%CI: 0.136-0.275 and OR: 0.128, 95%CI: 0.050-0.329; respectively) and LF (OR: 0.63, 95%CI: 0.406-0.976 and OR: 0.425, 95%CI: 0.286-0.632; respectively). No significant differences between AVP and CVC were demonstrated. Limited data suggests no major impact of different approaches on infectious and bleeding complications. Initial CVC approach required significantly more often an alternate/additional venous access for lead placement, compared to both AVP and SVP. No differences between these two were identified. CONCLUSION: Both AVP and CVC seem to decrease incident pneumothorax and LF, compared to SVP. Initial AVP approach seems to decrease the need of alternate venous access, compared to CVC. These results suggest that AVP should be further clinically tested.

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-diabetic agents that block the reabsorption of glucose in the proximal convoluted tubule of the nephron, thereby contributing to glycosuria and lowering blood glucose levels. SGLT2 inhibitors have been associated with improved cardiovascular outcomes in patients with diabetes, including a reduced risk of cardiovascular death and hospitalizations for heart failure. Recently, DAPA-HF and EMPEROR REDUCED trials showed the beneficial cardiovascular effect of SGLT2 inhibitors in patients with heart failure with consistently reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Moreover, some exploratory studies suggested that these drugs improve Left Ventricular (LV) systolic function and oppose LV adverse remodeling in patients with HFrEF. However, the exact mechanisms that mediated for this benefit are not fully understood. Beyond glycemic control, enhanced natriuresis, increased erythropoiesis, improved endothelial function and changes in myocardial metabolism may all play an active role in SGLT2 inhibitors' cardiovascular benefits. A deep understanding of the pathophysiological interplay is key to define which HF phenotype could benefit more from SGLT2 inhibitors. Current evidence on the comparison of different HF etiologies is limited to posthoc subgroup analysis of DAPA-HF and EMPEROR-REDUCED, which showed similar outcomes in patients with or without ischemic HF. On the other hand, in earlier studies of patients suffering from diabetes, rates of classic ischemic endpoints, such as myocardial infarction, stroke or coronary revascularization, did not differ between patients treated with SGLT2 inhibitors or placebo. The aim of this review is to discuss whether SGLT2 inhibitors may improve prognosis in patients with ischemic HF, not only in terms of reducing re-hospitalizations and improving LV function but also by limiting coronary artery disease progression and ischemic burden.

BACKGROUND: Interventional cardiologists prefer the right radial artery (RA) approach for coronary angiography and interventions, mainly for ergonomic reasons. However, the use of the left RA presents certain advantages, and the snuffbox approach has further potential advantages, including lower probability for RA occlusion, avoidance of direct puncture of the RA (thus maintaining its suitability for use as a graft), as well as easier and faster hemostasis. METHODS: Consecutive patients scheduled for coronary catheterization were included, using the left distal RA (ldRA) in the anatomical snuffbox as the default vascular access site. RESULTS: Out of 2034 consecutive cases, the ldRA was used as initial vascular access in 1977 patients (97.2%). The procedural failure rate was 9.9% (21.9% inability to puncture the artery, 75.0% inability to advance the wire, 3.1% other reasons). There was a sharp decrease in failure rate after about the first 200 cases (20.8% in the first decile vs 8.7% throughout the rest of the caseload; P<.001). No or very weak palpable pulse was the most important predictor of failure (odds ratio, 16.0; 95% confidence interval, 11.2-23.1; P<.001), in addition to older age, small stature, and female gender (although, after adjustment for height, the latter was no longer significant). CONCLUSION: In a large series of consecutive patients scheduled for left heart catheterization, through a period of 12 months, with virtually no exclusions except those few imposed by anatomy or compelling clinical needs, the ldRA arterial access approach was shown to be highly effective, feasible, and safe.

BACKGROUND: The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal thickness (CT), as assessed via optical coherence tomography (OCT), is poorly understood. OBJECTIVES AND DESIGN: Studies including hypertensive adults and normotensive controls undergoing OCT were evaluated for inclusion in this meta-analysis. The primary endpoint was CT difference between hypertensive and normotensive adults. DATA SOURCES AND METHODS: We conducted a systematic review and after searching 1011 results from MEDLINE, ClinicalTrials.gov, medRxiv and Cochrane Library, six studies were deemed eligible and were pooled according to a random-effect model. RESULTS: A statistically significant reduction in choroidal thickness was found in hypertensive adults ( = 454) as compared with normotensive controls ( = 365) [mean difference: -0.77; 95% confidence intervals: (-1.20, -0.34);  = 0.0004]. The main limitations of this meta-analysis are the relatively small population included and the high statistical heterogeneity (  = 87%) among the various studies. Of note, after excluding one study the heterogeneity was markedly reduced. CONCLUSION: Choroidal thickness is reduced among hypertensive subjects compared with normotensive controls. This finding mandates further examination in the context of long-term clinical outcomes.

Isolated coronary artery ectasia (CAE) is a relatively rare clinical entity, the pathogenesis of which is poorly understood. More and more evidence is accumulating to suggest a critical inflammatory component. We aimed to elucidate any association between neutrophil to lymphocyte ratio and coronary artery ectasia. A systematic MEDLINE database, ClinicalTrials.gov, medRxiv, Scopus and Cochrane Library search was conducted: 50 studies were deemed relevant, reporting on difference in NLR levels between CAE patients and controls (primary endpoint) and/or on high-sensitive CRP, IL-6, TNF-a and RDW levels (secondary endpoint), and were included in our final analysis. (PROSPERO registration number: CRD42021224195). All inflammatory biomarkers under investigation were found higher in coronary artery ectasia patients as compared to healthy controls (NLR; SMD = 0.73; 95% CI: 0.27-1.20, hs-CRP; SMD = 0.96; 95% CI: 0.64-1.28, IL-6; SMD = 2.68; 95% CI: 0.95-4.41, TNF-a; SMD = 0.50; 95% CI: 0.24-0.75, RDW; SMD = 0.56; 95% CI: 0.26-0.87). The main limitations inherent in this analysis are small case-control studies of moderate quality and high statistical heterogeneity. Our findings underscore that inflammatory dysregulation is implicated in coronary artery ectasia and merits further investigation.

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

BACKGROUND: Acute myocardial infarction (MI) is a major clinical manifestation of coronary artery disease. Post-MI morbidity and mortality can be reduced by lifestyle changes and aggressive risk factor modification. These changes can be applied more effectively if the patient is actively involved in the process. The hypothesis of this study was that an educational programme in post-MI patients could lead to reduced incidence of cardiovascular events. METHODS: Post-MI patients were prospectively randomised into two groups. Patients in the intervention arm were scheduled to attend an 8-week-long educational programme on top of usual treatment, while controls received optimal treatment. The primary endpoint was the composite of all-cause death, MI, cerebrovascular event and unscheduled hospitalisation for cardiovascular causes. Endpoint adjudication was blinded. RESULTS: 329 patients (238 men) were included, with a mean follow-up time of 17±4 months. In the primary analysis, mean primary end point-free survival time was 597 days (95% CI 571 to 624) in controls, compared with 663 days (95% CI 638 to 687) in the intervention group (p<0.001). The HR in the univariate Cox regression analysis was 0.48 (95% CI 0.32 to 0.73; p=0.001). The raw rates of the primary endpoint were 20.8% (6 deaths, 13 MIs, 2 strokes and 14 hospitalisations) vs 36.6% (8 deaths, 22 MIs, 7 strokes and 22 hospitalisations), respectively (OR 0.46, 95% CI 0.28 to 0.74; p=0.002). CONCLUSION: These results suggest that a relatively short adult education programme offered to post-MI patients has beneficial effects, resulting in reduced risk of cardiovascular events. TRIAL REGISTRATION NUMBER: NCT04007887.

Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic variability, impairs phosphatidylinositol 3‑kinase (PI3K)/protein kinase B signaling pathway. This pathway holds a central role in atrial electrical and structural remodeling responsible for arrhythmia initiation and maintenance. The molecular ''footprint'' of T1DM in atrial myocytes seems to involve a state of increased oxidative stress, impaired glucose transportation, ionic channel dysregulation and eventually fibrosis. On the contrary only a few clinical studies have examined the role of T1DM as an independent risk factor for AF development, and are discussed here. Further research is needed to solidify the real magnitude of this association and to investigate the clinical implications of PI3K molecular signaling pathway in atrial fibrillation management.

Colchicine's medical evolution is historically bound to the Mediterranean basin, since remarkable researchers from this region underscored its valuable properties. With the passing of years colchicine became an essential pharmaceutical substance for the treatment of rheumatologic and cardiovascular diseases. In light of recent findings, the therapeutic value of colchicine has grown. In clinical practice, colchicine remains underutilized in view of its proven efficacy and safety. Its complex pharmacokinetics and multifaceted anti-inflammatory role remain under investigation. The current review addresses the safe administration of colchicine in view of key drug to drug interactions. Finally, we are briefly presenting colchicine's future potential applications.

In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine's immunomodulating capacity in view of hindering coronavirus complications.

Stereotactic ablative radiotherapy (SABR) is highly focused radiation therapy that targets well-demarcated, limited-volume malignant or benign tumors with high accuracy and precision using image guidance. Stereotactic arrhythmia radioablation (STAR) applies SABR to treat cardiac arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF), and has recently been a focus in research. Clinical studies have demonstrated electrophysiologic conduction blockade and histologic fibrosis after STAR, which provides a proof of principle for its potential for treating arrhythmias. This review will present the basic STAR principles, available clinical study outcomes, and how the technique has evolved since the first pre-clinical study. In addition to the clinical workflow, focus will be given on the process for stereotactic radiotherapy Quality Assurance (QA) tests, as well as the need for establishing a standardized QA protocol. Future implications and potential courses of research will also be discussed.

The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here.

The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.

Transcatheter aortic valve implantation (TAVI) led to the foundation of the subspecialty of structural heart interventions and created an emerging area of clinical and technical issues. Soon after TAVI introduction into clinical practice, boundaries were expanded with utilization of valve-in-valve (V-i-V) techniques. V-i-V comprised a diverse subset of patients including TAVI within TAVI, TAVI within a degenerated surgically implanted bioprosthesis, or even TAVI-in-TAVI-in-surgical bioprosthesis. In the present review, we summarize the available literature and present initial experience on the field in Greece.

Patient involvement in therapeutic strategies leading to lifestyle changes and increasing adherence to beneficial treatment is important for high risk coronary artery disease patients. The hypothesis of the present substudy was that a program of education specifically structured to educate postmyocardial infarction patients would lead to measurable differences in specific indices of cardiovascular risk. Post-MI patients were randomly assigned to 2 groups. Patients in the intervention arm attended an 8-week long educational program in addition to usual treatment and controls received standard treatment. Low-density lipoprotein cholesterol, systolic blood pressure, body-mass index, and glycosylated hemoglobin were assessed at baseline and at 12 months (values are reported as median [interquartile range]). One hundred ninety-eight consecutively randomized patients were included in the present substudy. The median change in Low-density lipoprotein cholesterol was -54 (-45 to [-62]) mg/dl in the intervention group as compared with -35 (-28 to [-43]) mg/dl in controls (p <0.001). Systolic blood pressure change was -7.5 (-15.3 to 0.3) mm Hg and -3.0 (-11.8 to 2.8) mm Hg, respectively (p = 0.011). The median change in body-mass index was 0.0 (-3.0 to 3.0) kg/m as compared with 2.0 (-1.0 to 3.9) kg/m, respectively (p = 0.002). The reduction in glycosylated hemoglobin was significant in both groups with a median absolute change of -0.29 (-1.11 to 0.09) % in the intervention group and -0.24 (-0.69 to 0.06) % in controls (p = 0.168). If only diabetic patients were considered, the change was -0.65 (-1.3 to [-0.23]) % in the intervention group versus -0.41 (-0.74 to [-0.07]) % in controls (p = 0.021). In conclusion, a relatively short patient education program may have long-lasting effects on established modifiable markers of cardiovascular risk.

AIM: To characterize different patterns of variability of three repeated within-visit blood pressure (BP) readings and to determine the prevalence of specific variation trends in systolic (SBP), diastolic (DBP) blood pressure and pulse pressure (PP). METHODS: Data from 53 737 subjects from the National Health and Nutrition Examination Survey were analyzed. In each subject, three consecutive BP measurements were performed with a minimum time-interval of at least 30 s. We propose three patterns of within-visit BP variability (separately for SBP, DBP and PP): (1) increasing trend (BP3 > BP2 > BP1); (2) decreasing trend (BP1 > BP2 > BP3) and (3) no trend (BP3 ≈ BP2 ≈ BP1). A threshold of minimum change (ΔP > 3 mmHg) between BP1-BP2 and BP2-BP3 was also applied as a prerequisite for the definition of these trends. RESULTS: An increasing trend was observed among three consecutive measurements of SBP, DBP and PP in 7.4, 10.4 and 10.2%, respectively. When a minimum threshold of 3 mmHg was set the respective increasing trends were observed in 1.8, 2.9 and 4.4%, respectively. There was a higher prevalence of decreasing trend within three consecutive SBP, DBP and PP readings: 17, 13.1 and 16.2%, respectively, whereas using a threshold of ΔP >3 mmHg the respective prevalence was 6.3, 4.1 and 7.7%. A maximum absolute difference >10 mmHg within triplicate of SBP/DBP/PP readings was observed in 12.9, 13 and 29.4%, respectively. In the era of personalized medicine, these patterns are well worth further investigation concerning their pathophysiologic and clinical relevance.

OBJECTIVE: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. METHODS: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. RESULTS: Trial results will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).

BACKGROUND: Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension, arteriovenous malformations, or trauma. However, it can also present in patients receiving antithrombotic drugs, either anticoagulants such as acenocoumarol/warfarin-novel oral anticoagulants or antiplatelets, for the prevention and treatment of thromboembolic disease. OBJECTIVE: The purpose of this review is to present current bibliographic data regarding ICH irrespective of the cause, as well as post-hemorrhage use of antithrombotic agents. Moreover, this review attempts to provide guidelines concerning the termination, inversion, and of course resumption of antithrombotic therapy. METHODS AND MATERIALS: We reviewed the most recently presented available data for patients who dealt with intracerebral hemorrhagic events while on antithrombotic agents (due to atrial fibrillation, prosthetic mechanical valves or recent/recurrent deep vein thrombosis). Furthermore, we examined and compared the thromboembolic risk, the bleeding risk, as well as the re-bleeding risk in two groups: patients receiving antithrombotic therapy versus patients not on antithrombotic therapy. CONCLUSION: Antithrombotic therapy is of great importance when indicated, though it does not come without crucial side-effects, such as ICH. Optimal timing of withdrawal, reversal, and resumption of antithrombotic treatment should be determined by a multidisciplinary team consisting of a stroke specialist, a cardiologist, and a neurosurgeon, who will individually approach the needs and risks of each patient.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. OBJECTIVE: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN, SETTING, AND PARTICIPANTS: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. INTERVENTION: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. MAIN OUTCOMES AND MEASURES: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. RESULTS: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04326790.

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

The use of mobile health (mHealth) in the field of medicine is constantly evolving and advancing. Arterial hypertension, a major modifiable cardiovascular risk factor with a high prevalence in the general population, frequently remains underdiagnosed and thus untreated. Furthermore, the majority of hypertensive patients fail to achieve blood pressure target levels. The purpose of this review is to identify and evaluate current use of mHealth strategies, with focus on mobile phones, smartphones and applications, in the management of patients with arterial hypertension. Current mobile technology has the capacity to inform and motivate the general public for timely diagnosis of hypertension, to facilitate communication between physicians and patients, to aid in the monitoring of blood pressure levels and the optimization of treatment and to promote, in general, a healthy lifestyle and assist in the management of other cardiovascular risk factors. There is potential for positive impact of mHealth technology in the management of arterial hypertension, as well as probable detrimental effects that warrant caution. The research in this field is ongoing and future well-conducted studies are needed in order to establish the use of mobile technology in arterial hypertension management.

Obesity is a major risk factor for the development of chronic heart failure (CHF) and does not only pose diagnostic challenges, but also has prognostic implications for these patients. Paradoxically, obese patients with CHF have a better prognosis than thinner individuals. In recent years, it has been demonstrated that the adipose tissue, even in patients with HF, is not always detrimental, and that obesity may coexist with a phenotype of benign adiposity without systemic metabolic abnormalities. Experimental data have shown that natriuretic peptides (NPs), and in particular brain natriuretic peptide (BNP), play a major role in the communication of the heart with the adipose tissue. Body fat distribution and adipose tissue function show a large degree of heterogeneity among depots and may explain the complex relationship between NPs and body fat. NPs can affect both the quality and the behaviour of fatty tissue, promoting a healthy adipocyte phenotype, and can favourably affect body fat metabolism. In this article, we review the existing literature on the bidirectional effects of BNP and adipose tissue in HF and highlight the complexity of this relationship.

INTRODUCTION: There is one mathematical element with strong historical and philosophical background that exhibits remarkable properties and applications; the golden ratio (phi). Mathematically, the golden ratio equals approximately 1.61803. A rather provocative geometrical analysis of the arterial pulse according to the golden ratio was recently described, and herein, we aim to set out the hypothesis that individuals with blood pressure (BP) values that follow the golden ratio may have different prognosis than those whose BPs deviate from the divine proportions. MATERIALS AND METHODS: We used published data from the National Health and Nutrition Examination Survey during 1999-2010. RESULTS: We found that the deviation of the BP values from the golden ratio is independently associated with all-cause mortality. CONCLUSIONS: This observation stimulates further research of the potential utility of the golden ratio of BP values on the diagnosis and prediction of BP-related abnormalities and risk.

PURPOSE: The goal of this review was to summarize, analyze, and compare trials studying the efficacy of colchicine in the prevention of atrial fibrillation (AF) post-operatively (POAF) and post-catheter ablation. Ongoing studies and current guidelines are also presented and reviewed. METHODS: Published studies on the field were identified through a literature search of the PubMed and clinicaltrials.gov databases. FINDINGS: Four original studies regarding POAF, two original studies regarding post-catheter ablation AF, and six meta-analyses were identified. In addition, the 3 most recent guidelines/expert consensus documents were scrutinized. IMPLICATIONS: AF occurs frequently after cardiac surgery (POAF) and catheter pulmonary vein isolation (postablation AF) and is associated with increased cardiovascular morbidity. A number of trials over the last few years have investigated the role of colchicine in the prevention of POAF and postablation AF targeting the local and systemic inflammatory process that leads to initiation and maintenance of AF. Available data imply that colchicine may have a preventive role in POAF and/or postablation AF. However, certain limitations of these studies underline the need for further investigation.

BACKGROUND: Isolation of the pulmonary veins (PVI) has become a mainstay in atrial fibrillation (AFib) therapy. Lesions in left atrial tissue lead to scar formation and this may affect left atrial function. METHODS: Patients with paroxysmal AFib were randomly assigned in a 1:2 allocation scheme to radiofrequency (RF) ablation or cryoballoon. Real-time three-dimensional echocardiography was performed (under sinus rhythm in all cases) before ablation and at 1 and 3 months to evaluate the left atrial functional indices. The primary outcome measure was change in left atrial ejection fraction (LAEF) at 1 month. RESULTS: 120 patients were randomized (80 to cryoballoon, 40 to RF). The absolute change in LAEF at 1 month was 4.0 (Q1-Q3, -0.1to 7.6)% in the cryoballoon group and -0.8 (Q1-Q3, -1.9 to 0.9)% in the RF group (P < 0.001 for the comparison between groups). At 3 months, the corresponding changes were 6.7 (Q1-Q3, 3.4-11.2)% and 0.7 (Q1-Q3, -0.7 to 3.5)%, respectively (P < 0.001). Overall, the rate of patients with lower LAEF at 3 months compared to baseline was 2.5% in the cryoballoon group and 32.5% in the RF group (P < 0.001). AFib recurrence rate at 6 months was higher in patients with decreased LAEF (odds ratio, 6.2; 95% confidence interval, 2.0-19.5; P = 0.002). CONCLUSION: The Cryo-LAEF study prospectively compared the effects of RF and cryoballoon ablation on left atrial function. Both at 1 and 3 months postablation, LAEF was either improved or stable in both ablation groups.

Jules Cotard (1840-1889), a Parisian neurologist, described a syndrome of delirium negations which was later named after him. Some physicians in antiquity and medieval times, especially in Asia, have noticed this syndrome and categorized it as a symptom of melancholy. They have presented it as a "walking corpse syndrome", inflicting most probably veteran soldiers after suffering during ferocious battles, presenting the first cases of a post war traumatic stress disorder. Philotimus (3rd-2nd century BC) was the first to record it around 3rd century BC, and proposed a simple but pioneering treatment, by just putting a lead hat on the men's heads. Although various combined treatment strategies were proposed by modern psychiatry including pharmaceutical, electroconvulsive therapy, behavioural therapy and supportive psychotherapy, it seems that in antiquity a simple external intervention of supportive therapy was the main concept of confrontation, while drug administration was to be avoided.

AIM: High position of the self-expandable bioprosthesis CoreValve/Evolut R has been proved to affect immediate hemodynamics of the valve. Whether this may have any impact on long-term procedural outcome has not been defined yet. The purpose of this study was to assess whether the final position of aortic bioprosthesis affects its long-term functionality. METHOD: Consecutive patients (pts) who underwent successful TAVI procedure were evaluated and separated into 2 groups according to the implantation depth (ID): Group I: pts with 4 mm

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3-6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3-12 months. Four non-randomized trials were identified, comparing single . dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.

Invasive treatment in peripheral artery disease (PAD) has evolved as a viable alternative to surgical treatment. However, beyond the common pathophysiological substrate, as far as treatment is concerned, each site of atherosclerotic disease (subclavian and vertebral arteries; carotid arteries; intracranial arterial tree; renal arteries; lower extremity arteries) features unique characteristics. Treatment options include medical treatment, endovascular management and/or surgery. Sound clinical evaluation is required as individual patient assessment often limits intervention options, while available data regarding benefits of invasive and surgical management are questioned by advances in medical treatment. In the present article, we aim to summarize existing evidence and guidance on the role of invasive procedures in PAD.

Post-operative atrial fibrillation (POAF) is a frequent entity increasing hospitalization duration, stroke and mortality. In the recent years, a few studies have sought to investigate the potential effect of colchicine in POAF prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In the present review article, we intend to provide a synopsis of clinical practice guidelines, summarize and critically approach current evidence for or against colchicine as a means of POAF prevention.

The plants of the Colchicum family were known during the archaic period in Greece for their deleterious properties. Later on, they were used for the treatment of podagra. The treatment was introduced by the ancient Greek physicians and passed on to the Byzantine and Arabian physicians to endure until nowadays. The first plant was most probably named "Medea" from the notorious Colchican witch. As the most common member of the family blossoms in autumn, the plant was named Colchicum autumnale. Various nominations were also used, such as Ephemeron, Hermodactyl, Anima articulorum and Surugen. Our article discusses them, while at the same time presents the most notable authorities who have used Colchicum plants in herbal medicine and toxicology.

BACKGROUND: Bacterial infections in cirrhotic patients remain a challenge. Presepsin has been proposed as a valuable sepsis biomarker. We aimed to assess plasma presepsin levels in uncomplicated cirrhotic patients and to correlate them with liver disease severity and complicating events, defined as documented bacterial infection with or without concomitant portal hypertension-related bleeding, or bleeding without documented bacterial infection, with or without acute kidney injury. METHODS: We prospectively evaluated the presepsin levels of 108 consecutive uncomplicated cirrhotic patients with compensated (55, 50.9%) or decompensated (53, 49.1%) cirrhosis. During the follow up, 20 patients were reevaluated for a complicating event. RESULTS: Mean baseline presepsin levels of the entire population were 440.4 pg/mL. Patients with decompensated cirrhosis exhibited significantly higher baseline levels than patients with compensated cirrhosis (599.1±492.2 vs. 287.5±130.5 pg/mL, P<0.001). In complicated cirrhotic patients, admission levels were remarkably higher than baseline (1438.0±1247.2 vs. 725.3±602.8 pg/mL, P<0.001), especially in those who developed acute kidney injury compared to those who did not (1827.3±1118.8 vs. 1048.7±1302.1 pg/mL, P<0.05). Baseline presepsin levels, using a cutoff of 607.5 pg/mL, could predict liver disease-related 3-month mortality with 77.8% sensitivity and 86.9% specificity: area under the receiver operating characteristic curve 0.825; 95% confidence interval 0.684-0.967; P<0.01. CONCLUSIONS: Plasma presepsin levels are elevated in uncomplicated cirrhotic patients, especially in those with advanced liver disease, and rise further in those complicated by an event. Baseline presepsin levels in cirrhotic patients could be used as an additional marker, along with the model for end-stage liver disease score, to predict short-term outcomes.

BACKGROUND: Left atrial appendage (LAA) functional modification in the context of pulmonary vein isolation has been a focus point of research and LAA emptying flow velocity (LAAEFV) is considered to reflect LAA contractility, stunning, and fibrosis. OBJECTIVE: In the present study, we sought to prospectively evaluate short-term LAAEFV changes after radiofrequency (RF) or cryoballoon ablation in paroxysmal AF. METHODS: This was a prospective substudy of the Effect of Cryoballoon and RF Ablation on Left Atrial Function (CryoLAEF) study (ClinicalTrials.gov Identifier: NCT02611869). Thirty patients, randomly assigned to RF or cryoablation, were prospectively followed. Transesophageal echocardiograms were performed at baseline and at 3 months postablation to measure LAAEFV. RESULTS: All measurements were performed in sinus rhythm. Overall, LAAEFV was 44.2 [38.5-62.8] cm/s at baseline and was increased to 70.8 [64.8-77.6] cm/s at 3 months' postablation (P < 0.001). Baseline LAAEFV was 52.5 [37.7-68.0] cm/s in the RF group and 42.8 [38.7-52.9] cm/s in the CryoBalloon group (P  =  0.653). At 3 months, the corresponding values were 68.5 [61.9-76.6] cm/s and 73.9 [69.2-79.9] cm/s, respectively (P  =  0.081 for the difference between the two groups at 3 months). The median change in LAAEFV was 11.0 [4.7-26.2] cm/s in the RF group versus 29.6 [15.8-37.0] cm/s in the CryoBalloon group (P  =  0.033). CONCLUSION: LAA function is improved after catheter ablation with RF or balloon cryoablation in patients with paroxysmal AF, evaluated while in sinus rhythm both at baseline and on follow-up.

Heart failure (HF) and AF frequently coexist and are involved in a vicious cycle of adverse pathophysiologic interactions. Applying treatment algorithms that have been validated in the general AF population to patients with AF and HF may be fraught with risks and lack effectiveness. While firm recommendations on using catheter ablation for AF do exist, the subset of patients also suffering from HF needs to be further evaluated. Observational data indicate that a significant number of ablation procedures are performed in patients with coexistent HF. Initial randomised data on outcomes are encouraging. Apart from sinus rhythm maintenance, benefits have been observed in terms of other significant endpoints, including left ventricular ejection fraction, quality of life, exercise capacity and hospital readmissions for HF. Limited existing data on survival are also promising. In the present article, observational and randomised studies along with current practice guidelines are summarised.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

OBJECTIVE: Neoangiogenesis is pathophysiologically related to atherosclerotic plaque growth and vulnerability. We examined the in vivo performance of a computational method using contrast-enhanced intravascular ultrasound (CE-IVUS) to detect and quantify aortic wall neovascularization in rabbits. We also compared these findings with histological data. METHODS: Nine rabbits were fed with a hyperlipidemic diet. IVUS image sequences were continuously recorded before and after the injection of a contrast agent. Mean enhancement of intensity of a region of interest (MEIR) was calculated using differential imaging algorithm. The percent difference of MEIR before and after the injection of microbubbles (d_MEIR) was used as an index of the density of plaque or/and adventitial neovascularization. Aortic segments were excised for histological analysis. RESULTS: CE-IVUS and histological analysis were performed in 11 arterial segments. MEIR was significantly increased (~20%) after microbubble injection (from 8.1±0.9 to 9.7±1.8, p=0.016). Segments with increased VV/neovessels in the tunica adventitia (histological scores 2 and 3) had significantly higher d_MEIR compared with segments with low presence of VV/neovessels (score 1); 40.5±22.9 vs. 8±14.6, p=0.024, respectively. CONCLUSION: It is possible to detect VV or neovessels in vivo using computational analysis of CE-IVUS images, which is in agreement with histological data. These findings may have critical implications on vulnerable plaque assessment and risk stratification.

Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of death and disability worldwide. However, the mortality of MI has declined dramatically over the past several decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin converting enzyme inhibitors) and approaches to restore tissue perfusion (percutaneous coronary intervention and cardiopulmonary bypass). Animal studies have been shown that these treatments have been effective in reducing acute myocardial ischemic injury and limiting MI size. The paradox is that the process of reperfusion can itself amplify cell injury and death, known as myocardial ischemia-reperfusion injury (I/R). Intensive research has uncovered several complex mechanisms of cardiomyocyte damage after reperfusion,and potential therapeutic targets for preventing I/R. Importantly, it is now recognized that excessive elevation of intracellular and mitochondrial Ca2+during reperfusion predisposes the cells to hypercontracture, proteolysis and mitochondrial failure and eventually to necrotic or apoptotic death. These enormous alterations in cytosolic Ca2+ levels are induced by the Ca2+ channels of the sarcolemma(L-Type Ca2+channels, sodium/calcium exchanger), the endoplasmic/ sarcoplasmic reticulum (SERCA ATPase) and ryanodine receptors, SOCE(store-operated calcium entry), lysosomes and others, which are modified by I/R injury. The overall goal of this review is to describe the different pathways that lead to I/R injury via Ca2+ overload, focus on recent discoveries and highlight prospects for therapeutic strategies for clinical benefit.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been used prior to valve implantation of a self-expandable valve as part of the transcatheter aortic valve implantation (TAVI) procedure. We aimed to evaluate the impact of BAV prior to TAVI. METHODS: We retrospectively studied 203 consecutive patients who were treated either with (pre-BAV-TAVI group) or without BAV (D-TAVI group). Implantation depth (ID) was angiographically measured at non-coronary cusp (NCC) and left coronary cusp (LCC) at: the starting point (stage-1), before (stage-2), and after (stage-3) final bioprosthesis release. Paravalvular regurgitation (PVR) and 1-year clinical follow-up were recorded. RESULTS: Overall, from stage-1 to stage-3, prosthesis migrated toward the left ventricle, in both cusps and groups. At NCC a forward migration was observed from stage-1 to stage-2 in both groups (p<0.001). In the pre-BAV-TAVI group only, at NCC, an upward migration decreased the ID from stage-2 to stage-3 (p=0.022). PVR ≥grade 2, immediately after expansion was more frequently observed in pre-BAV-TAVI group (41% vs 22%, respectively; p=0.024). However, PVR was similar at discharge. Clinical parameters were comparable between the two groups. CONCLUSIONS: The use of BAV prior to TAVI may have an impact on device final position, but not on short- and long-term clinical outcome.

BACKGROUND: Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly. OBJECTIVE: The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT). METHODS: This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms. RESULTS: Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders. CONCLUSION: In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause).

Carotid atherosclerosis represents a primary cause for cerebrovascular ischemic events and its contemporary management includes surgical revascularization for moderate to severe symptomatic stenoses. However, the role of invasive therapy seems to be questioned lately for asymptomatic cases. Numerous reports have suggested that the presence of neovessels within the atherosclerotic plaque remains a significant vulnerability factor and over the last decade imaging modalities have been used to identify intraplaque neovascularization in an attempt to risk-stratify patients and offer management guidance. Contrast-enhanced ultrasonography of the carotid artery is a relatively novel diagnostic tool that exploits resonated ultrasound waves from circulating microbubbles. This property permits vascular visualization by producing superior angiography-like images, and allows the identification of vasa vasorum and intraplaque microvessels. Moreover, plaque neovascularization has been associated with plaque vulnerability and ischemic symptoms lately as well. At the same time, attempts have been made to quantify contrast-enhanced ultrasonography signal using sophisticated software packages and algorithms, and to correlate it with intraplaque microvascular density. The aim of this review was to collect all recent data on the characteristics, performance, and prognostic role of contrast-enhanced ultrasonography regarding carotid stenosis management, and to produce useful conclusions for clinical practice.

Transcatheter interventions for structural heart disease represent an emerging field in interventional cardiology. Undoubtedly, there is an absolute necessity for antiplatelet and/or anticoagulation treatment prior, during and post such interventions. However, currently administered regimens are mainly based in expert consensus recommendations. In the present review we aim to summarize data regarding anti platelet and/or anticoagulation treatment in the following transcatheter structural heart interventions: left atrial appendage closure, atrial septal defect closure, patent foramen oval closure, paravalvular leak closure.

BACKGROUND: Intracerebral hemorrhage is the pathological accumulation of blood within the brain. It is a type of stroke more likely to be lethal or to severely disable the patient and results from a wide variety of causes. On the other hand antithrombotic therapy is used for the prevention or/and the therapy of thromboembolic episodes. Antithrombotic drugs are very effective in reducing risk or mortality rate after a thromboembolic event, yet they are associated with significant hemorrhages. OBJECTIVE: The aim of this article is to review current literature for intracerebral hemorrhage and antithrombotic therapy and offer recommendations on the reversal, the discontinuation and the resumption of antithrombotic therapy. METHODS AND MATERIALS: Current literature has been reviewed for intracerebral hemorrhage associated with three major categories of patients, those with atrial fibrillation, those with prosthetic mechanical valves and those with venous thromboembolism. Antithrombotic therapy is categorized in antiplatelet agents and anticoagulants. The risk of intracerebral hemorrhage, of a thromboembolic event and of a rebleeding with or without antithrombotic therapy was also reported. CONCLUSION: Although no one can deny the usefulness of antithrombotic therapy a therapeutic strategy should be developed in order to optimize the clinical decision of stopping, reversing and restarting antithrombotic treatment. This review concludes in strong recommendations, yet a multidisciplinary panel by a stroke physician or neurologist, a cardiologist, a neuroradiologist and a neurosurgeon should evaluate the benefits and the risks for each patient and decide the best therapeutic strategy.

OBJECTIVES: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. METHODS: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. RESULTS: RBCm count was correlated with CK-MB AUC (Spearman's ρ = 0.83, p < 0.001). The CK-MB AUC values per RBCm quartile (lower to upper) were: 3,351 (2,452-3,608), 5,005 (4,450-5,424), 5,903 (4,862-10,594), and 8,406 (6,848-12,782) ng × h/ml, respectively. From lower to upper quartiles, the maximal troponin I values were: 42.2 (23.3-49.3), 49.6 (28.8-54.1), 59.2 (41.4-77.3), and 69.1 (48.0-77.5) ng/ml (p = 0.005). In multivariable analysis, RBCm remained a significant predictor of CK-MB AUC (standardized β = 0.63, adjusted p = 0.001). CONCLUSIONS: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury.

BACKGROUND: Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability. METHODS: Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response. RESULTS: According to most studies, CYP2C19 gene is the strongest genetic determinant. The novel antiplatelet agents prasugrel and ticagrelor, seem to overcome genetic restrictions but in expense of increased bleeding rates. Achieving a balance between adequate platelet inhibition and bleeding complications is challenging. CONCLUSION: Genetic screening may provide valuable guidance towards an efficient antiplatelet treatment. However, the lack of randomized controls trials testing the effect of a genotype-guided therapy, forbids the implementation of genetic testing into clinical practice.

Catheter ablation for rhythm control in atrial fibrillation has been recognized as an established treatment. Patients with atrial fibrillation suffer from an increased risk of thromboembolic events. Long-term stroke risk and mortality have been shown to be reduced after catheter ablation, still the procedure per se is associated with an additive peri-procedural thromboembolic risk. Maintenance of the thrombotic - bleeding equilibrium in such patients during interventional procedures is compelling. Lack of data from randomized studies along with the recent introduction of novel oral anticoagulants in clinical practice has resulted in a wide variance of antithrombotic treatment approaches. Procedural interruption of anticoagulants, switching of anticoagulation scheme (i.e. from novel oral anticoagulants to vitamin K antagonists), bridging with heparin, timing of re-initiation of therapy and/or utilization of novel oral anticoagulants have all been points of dispute. In the present review we present the available data regarding optimal peri-procedural anticoagulation strategies in patients undergoing catheter ablation for atrial fibrillation.

Over the course of the last 2 decades, the concept of remote ischemic conditioning (RIC) has attracted considerable research interest, because RIC, in most of its embodiments offers an inexpensive way of protecting tissues against ischemic damage inflicted by a number of medical conditions or procedures. Acute kidney injury (AKI) is a common side effect in the context of various medical procedures, and RIC has been suggested as a means of reducing its incidence. Outcomes regarding kidney function have been reported in numerous studies that evaluated the effects of RIC in a variety of settings (eg, cardiac surgery, interventions requiring intravenous administration of contrast media). Although several individual studies have implied a beneficial effect of RIC in preserving kidney function, 3 recently published randomized controlled trials evaluating more than 1000 patients each (Effect of Remote Ischemic Preconditioning in the Cardiac Surgery, Remote Ischaemic Preconditioning for Heart Surgery, and ERICCA) were negative. However, AKI or any other index of renal function was not a stand-alone primary end point in any of these trials. On the other hand, a range of meta-analyses (each including thousands of participants) have reported mixed results, with the most recent among them showing benefit from RIC, pinpointing at the same time a number of shortcomings in published studies, adversely affecting the quality of available data. The present review provides a critical appraisal of the current state of this field of research. It is the opinion of the authors of this review that there is a clear need for a common clinical trial framework for ischemic conditioning studies. If the current babel of definitions, procedures, outcomes, and goals persists, it is most likely that soon ischemic conditioning will be "yesterday's news" with no definitive conclusions having been reached in terms of its real clinical utility.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

BACKGROUND: The aim of this study was to evaluate how the spatial distribution of each plaque element, defined by intravascular-ultrasound virtual histology (IVUS-VH), may affect stent deployment even at high inflation pressures. METHODS: Thirty-two patients undergoing direct percutaneous coronary intervention and IVUS were evaluated. Fifty-two lesions were treated with drug-eluting stents. Pre-stenting lumen area and real (Rcssla) and average cross-sectional stent lumen area (Acssla) were measured along the whole lesion. Ideal cross-sectional stent lumen area (Icssla) was calculated. Plaque composition was characterized by IVUS-VH. The spatial distribution of each plaque element was quantified by a novel image analysis tool measuring the area and percentage of each plaque component that was adjacent to the lumen. Average stent deployment was defined as: [1 - (Icssla-Acssla)/Icssla]×100%. RESULTS: Stent expansion was significantly less at the site of maximum calcification compared to the average stent deployment (80±9% vs. 85±13%, P=0.044, respectively). Furthermore, wherever calcium was adjacent to the lumen, stent expansion was impaired compared to sites where calcium was non-luminal (70±23% vs. 80±9%, P=0.01, respectively). In contrast, at the site of maximum necrotic core, stent deployment showed a trend to be less compromised, compared to the average stent deployment. CONCLUSIONS: An interaction was found between plaque components and their distribution and stent deployment even at high inflation pressures.

Transcatheter aortic valve implantation (TAVI) is all the more used therapeutic option for patients suffering from symptomatic severe aortic valvular stenosis declined by surgeons because of high surgical risk. Given the high bleeding and ischemic risk of this vulnerable population, their antithrombotic treatment becomes a crucial issue. There is no consensus on antithrombotic treatment after TAVI and dual antiplatelet therapy (DAPT) with aspirin (indefinitely) and clopidogrel (1-6 months) is, in general, recommended. With regards to patients with an indication for oral anticoagulation (OAC), a combination of OAC plus aspirin or clopidogrel is commonly suggested. This review underscores that it is extremely difficult to compare different antithrombotic regimens in patients undergoing TAVI because of their variable demographic characteristics. Nevertheless, available data suggest that DAPT results to more bleeding events. Still, whether it positively affects ischemic episodes is doubtful. Ongoing trials are expected to draw a clearer picture on the field.

INTRODUCTION: Aortic stenosis is one of the most frequent valvulopathy of modern time necessitating interventional therapy when symptoms arise and stenosis becomes severe. First line treatment has traditionally been surgical aortic valve replacement (SAVR). However in the last decade transcatheter aortic valve implantation (TAVI) with bioprosthetic valves has proved to be a sound solution for high-risk for SAVR or inoperable patients. As expected implantation of the bioprosthetic device requires administration of antiplatelet regimen to the patients for a certain period. Atrial fibrillation (AF) may occur frequently during the peri-procedural period. In this background, the occurrence of AF after device implantation may be a challenging issue. METHODS: We performed a literature search of PubMed and Embase database. Published articles reporting the incidence, clinical implications and description of antithrombotic regimen of New-onset atrial fibrillation (NOAF) in individuals undergoing TAVI were considered eligible. Incidence, Implications and Antithrombotic Regimen: The overall occurrence of NOAF is reported to be 1%-32% after TAVI. Left atrial enlargement and transapical approach constitute independent predictors for NOAF. Additionally it has been shown that patients with AF face an increased risk of death irrespective of the type of AF. Patients, with a history of AF, present greater rate of death than individuals with NOAF. NOAF is responsible for cerebrovascular events (CVE) occurring in the subacute phase (days 1-30) after the procedure. The risk of stroke/transient ischemic attack after TAVI is increased at least two fold by the presence of atrial fibrillation. Empirically, a dual antiplatelet strategy has been used for patients undergoing TAVR, including aspirin and a thienopyridine. In cases where patients are in need of oral anticoagulation after TAVI a combination of aspirin or thienopyridine with acenocoumarol has been the preferred regimen. DISCUSSION: Despite the continuously crescent use of TAVI for patients with symptomatic severe aortic stenosis, there are still many aspects of this procedure to be clarified. A lack of data exists from the available clinical trials regarding the appropriate anticoagulation therapy for patients with greater risk for thromboembolic events. As a result, patient's treatment remains at the discretion of the physician. CONCLUSION: Limited data are available regarding the optimal therapeutic regimen in patients undergoing TAVI who need therapy for AF. Carefully designed clinical studies might further clarify the incidence and interrelation between atrial fibrillation and TAVI. The balance between the efficacy and risk of anticoagulation needs to be further clarified in patients undergoing TAVI.

In the 18(th) century clinical cardiology was based on pulse examination and auscultation by placing the ear directly on the patient's chest, while diagnosis of heart diseases was done in postmortem examination. In 1749, Jean-Baptiste de Sénac, physician of King Louis XV, published his work on the heart Traité de la structure du coeur, de son action et de ses maladies. It was the result of years of anatomical and physiological study, in an attempt to illuminate heart and its functions. Sénac recognized among several heart disorders, aortic regurgitation, mitral calcification, and mitral regurgitation. His work remained a landmark in valvular pathology and cardiology until the early 19(th) century.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.

BACKGROUND: 'Cover index' has been proposed to appraise the congruence between the aortic annulus and the device, with the assumption of not taking into account the actual device implantation depth. The aim of this study was to investigate whether the annulus-prosthesis mismatch, as expressed with the new proposed 'true cover index' according to actual implantation depth, can predict aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI). METHODS: Patients who had undergone TAVI with the self-expandable CoreValve device, were retrospectively studied. All available prosthesis sizes were ex-vivo scanned and the precise diameter at 0.3mm intervals along each device was measured. The 'true cover index' was evaluated, as a ratio of the following: 100×([prosthesis actual diameter at implantation depth-annulus diameter]/prosthesis actual diameter at implantation depth). AR was echocardiographically evaluated at discharge and 30days and classified as prominent if moderate, or trivial if none or mild. RESULTS: Overall, 120 patients who had undergone TAVI, were considered eligible for the study. 'True cover index' was statistically significantly lower among patients with prominent AR in comparison with trivial AR at discharge (5.7±4.8mm vs 9±5.1, p=0.025), as well as at one month post-TAVI (5.4±5.1mm vs 9.0±5.1, p=0.023), indicating increased AR for smaller index. After adjustment for severe annulus calcification, impaired baseline LVEF and previous valvuloplasty, it remained an independent predictor of one month prominent AR (OR: 0.854, CI: 0.730-0.999; p=0.048). 'True cover index' of <4.3 was shown to predict one-month prominent AR with sensitivity =75% and specificity =82.5%. CONCLUSIONS: 'True cover index' is strongly and independently correlated with the short and mid-term AR after CoreValve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has undeniably earned a prestigious post in the quiver of interventional cardiologists against symptomatic severe aortic stenosis. Cerebrovascular events are listed within the most frequent complications. METHODS: We performed a systematic search of EMBASE, MEDLINE, and the Cochrane library from inception to March 2016 for the following search terms (transcatheter AND antiplatelet) OR (transcatheter AND antithrombotic) to retrieve studies of dual antiplatelet treatment (DAPT) and single antiplatelet treatment (SAPT) in patients after TAVI to study thrombotic, hemorrhagic and cardiovascular events at 30 days post procedure. From a total of 208 records 4 studies met inclusion criteria. RESULTS: In the included studies, 286 patients were enrolled in the DAPT group and 354 patients in the SAPT group. There was no difference in all-cause mortality, cardiovascular mortality, stroke, and myocardial infraction 30 days post TAVI between DAPT and SAPT. However, patients in the DAPT group had a significantly increased incidence of lethal and major bleeding at 30 days of follow-up and the incidence of the combined end-point of stroke, spontaneous MI, all-cause mortality and major bleeding was significantly higher in the DAPT group in comparison to the SAPT group. CONCLUSION: DAPT compared to SAPT in patients after TAVI increases incidence of hemorrhagic events with no benefits in terms of thrombotic events and cardiovascular mortality. However, these data must be interpreted cautiously and the choice of DAPT over SAPT must be based on an individual patient characteristic according to medical practice criteria.

AIM: To investigate the frequency and timing of post-partum chronic hepatitis B virus (HBV) reactivation and identify its pre-partum predictors. METHODS: Forty-one hepatitis B e antigen (HBeAg)-negative chronic HBV infected pregnant women were prospectively evaluated between the 28th and the 32nd week of gestation. Subjects were re-evaluated at 3-mo intervals during the first post-partum year and every 6 mo during the following years. HBV DNA was determined using real-time reverse transcription polymerase chain reaction (Cobas TaqMan HBV Test) with a lower detection limit of 8 IU/mL. Post-partum reactivation (PPR) was defined as abnormal alanine aminotransaminase (ALT) levels and HBV DNA above 2000 IU/mL. RESULTS: Fourteen out of 41 women (34.1%) had pre-partum HBV DNA levels>2000 IU/mL, 18 (43.9%) had levels<2000 IU/mL and 9 (21.9%) had undetectable levels. Fourteen women were lost to follow-up (failure to return). PPR occurred in 8 of the 27 (29.6%) women evaluated, all within the first 6 mo after delivery (5 at month 3; 3 at month 6). Five of the 6 (83.3%) women with pre-partum HBV DNA>10000 IU/mL exhibited PPR compared with 3 of the 21 (14.3%) women with HBV DNA<10000 IU/mL (two with HBV DNA>2000 and the third with HBV DNA of 1850 IU/mL), P=0.004. An HBV DNA level≥10000 IU/mL independently predicted post-partum HBV infection reactivation (OR=57.02, P=0.033). Mean pre-partum ALT levels presented a non-significant increase in PPR cases (47.3 IU/L vs 22.2 IU/L, respectively, P=0.094). CONCLUSION: In the present study, PPR occurred in approximately 30% of HBeAg-negative pregnant women; all events were observed during the first semester after delivery. Pre-partum HBV DNA level>10000 IU/mL predicted PPR.

Aim of the present study was to record the antithrombotic approach in AF and non-AF patients undergoing TAVI, and to compare the efficiency of the used regimens combination. Antithrombotic approach of patients undergoing TAVI remains a challenging dispute. It becomes even more complex when need for anticoagulant treatment is required due to concurrent atrial fibrillation. Consecutive patients with severe symptomatic aortic stenosis treated with TAVI, were retrospectively studied. All patients were divided into two groups, matched to age, depending on the existence of atrial fibrillation. The primary end-point was the composite of MACE, while the secondary end-point was the occurrence of major bleeding at follow-up. A total of 80 patients were included in the study. Out of them, 20 patients (80.2 ± 5.4 years) suffered from concurrent atrial fibrillation. This group was matched with 20 patients (80.6 ± 3.7 years) with no need for anticoagulation. AF-group patients were treated with clopidogrel plus acenocoumarol for 3 months. Following that, acetylsalicylic acid plus acenocoumarol were prescribed. Non-AF patients were treated with 3 months clopidogrel plus acetylsalicylic acid followed by single acetylsalicylic acid medication. No statistical significant differences in MACE between AF and non-AF group were identified (p = 0.705, phi coefficient = 0.06) (mean follow-up 23.4 ± 14 months). Similarly, there was no statistical significant difference for bleedings among the AF and non-AF patient group (p = 0.658, phi coefficient = 0.14). In patients undergoing TAVI with CoreValve, with concurrent AF, treatment with clopidogrel plus acenocoumarol for 3 months, followed by acetylsalicylic acid plus acenocoumarol, seems safe and effective enough in long-term follow-up.

We report the first TAVI procedure in Greece to use the CoreValve Evolut-R (23 mm profile) bioprosthesis with the InLine sheath and the EnVeo loading guiding catheter in a patient with small anatomical characteristics (aortic annulus, access vessel) and severe comorbidities. The procedure was successfully conducted under general anesthesia through a surgically prepared, extensively calcified, left femoral artery.

Age-related macular degeneration (AMD) is one of the main causes of vision loss, especially in the elderly. The involvement of essential hypertension in its pathogenesis has been well covered in the literature since it was first recognized. Hemodynamic abnormalities appear to contribute to AMD, with the renin-angiotensin system playing a significant role. Many studies have demonstrated that high blood pressure is associated with lower choroidal blood flow and disturbed vascular homeostasis in these patients. In addition, AMD is characterized by abnormal neovascularization, to which angiotensin II and growth factors make a large contribution. Most epidemiological studies have found essential hypertension to be a risk factor for AMD. However, although all agree that the strongest predisposing factors are age and smoking, overall there is some inconsistency regarding the exact role of hypertension in its pathogenesis. In particular, there are no data in the literature to support the view that antihypertensive medication and the successful management of hypertension have a positive effect on the clinical outcome of AMD. This reinforces the data indicating that the cause of AMD is multifactorial and suggests that, although essential hypertension probably plays a role, in itself it is unlikely to be a major contributor to the future occurrence of AMD.

Inflammation plays a critical role in the atherosclerotic process in various vascular beds, starting from endothelial dysfunction and counting all stages of plaque development. The significant contribution of inflammation in the initiation and progression of atherosclerosis has been documented over many years but its contribution to the development of other cardiovascular disease remains unclear. Inflammatory process constitutes a basic part of pathogenic cascade of aortic diseases including those of aortic valve stenosis and aortic aneurysms. Thus, both of these entities are related with high rates of morbidity and mortality. Therefore, the need to detect and investigate indices representative of inflammation that will be easily measured and may reflect the process of these diseases, is mandatory. However, such biomarkers for aortic diseases that could have a significant prognostic value on survival via the early identification of high risk patients, in general, remain few. Therefore, the illumination of role of such biomarkers, will facilitate the understanding of the mechanisms in molecular and/or cellular level that are responsible for the creation of aortic disease. Such an approach may provide a pathophysiological basis for early diagnosis.

Very limited data exist on transcatheter aortic valve implantation (TAVI) in the setting of a preexisting mitral prosthesis regarding the technique, potential complications, and outcomes. Here, we report two cases of transfemoral TAVI with a self-expanding bioprosthesis (CoreValve; Medtronic, Inc) in patients who had previously undergone mitral valve replacement (one with an Omniscience and one with a St. Jude prosthesis). A brief literature review is also presented.

Biomarkers derived noninvasively from the aortic blood pressure (BP) waveform provide information regarding cardiovascular (CV) risk independently of brachial BP (bBP). Although body position has significant impact on the assessment of bBP, its effect on aortic hemodynamics remains unknown. This study investigated the changes in both brachial and aortic hemodynamics, between the supine and sitting position. In this randomized cross-over study, the bBP and the aortic pressure waveform were assessed after a 5 min rest (sitting and supine in randomized order); aortic BP, pulse pressure (PP) amplification, augmentation index (AIx) and subendocardial viability index (SEVR) were assessed. Sixty-one subjects were examined (36 males, mean age 50±12 years). Mean BP did not differ between the sitting and supine position (110.8±13.7 vs 110.9±14.9, respectively, P=0.945). However, significant difference between the sitting and supine position in brachial PP (45.9±16.0 vs 52.6±15.6, respectively, P<0.001), aortic PP (36.7±15.2 vs 43.1±13.9, P<0.001), PP amplification (1.28±0.1 vs 1.23±0.1, P<0.001), AIx (26.9±11.9 vs 31.1±10.2, P<0.001) and SEVR (179.6±25.7 vs 161.2±25.8, P<0.001) were found. Review of the literature identified underestimation of the role of body position on aortic hemodynamics. In conclusion, increased PP in both the aorta and brachial artery were found in the supine compared to the sitting position. Reduced PP amplification and SEVR were further observed in the supine position, due to increased pressure wave reflections (AIx).

The present study attempts to offer insight into the volume, cost, and productivity of the operation of a cardiac echocardiographic laboratory (echo-lab) in a major public hospital of Greece and thus to contribute, on a practical level, to the widening of knowledge in the strategic field of secondary and tertiary healthcare management. The conducted research includes the basic step of the deployment of a primary data registry in the echo-lab and unfolds in three levels, i.e. the variability measurement of the quantity and cost of medical services provided to different patient populations, the assessment of operating costs and the development of productivity indexes. The results show that the mean costs of provision do change among distinct patient populations. The most important, from a financial standpoint, population cluster appears to be the one corresponding to outpatients. Productivity indices presented in this analysis constitute an essential piece of information which the public healthcare system is currently largely lacking, and which, combined with the pricing and the diagnosis-related group coding system of hospitals, can be used to improve efficiency in the management of secondary and tertiary care.

Refractory angina pectoris constitutes a manifestation of severe ischemic heart disease that cannot be treated adequately either with conventional medication or with interventional techniques including percutaneous coronary angioplasty (PTCA). As a result, new therapeutic strategies, aiming on angiogenesis, were evolved in order to improve functional class and health related quality of life (HRQOL) indices. Among them, gene therapy constitutes a very promising alternative treatment for these patients. In this review, we will describe i) the definition of refractory angina ii) pathophysiology of angiogenesis, iii) routine as well as novel imaging techniques of neovascularization and iv) current treatment options for refractory angina. Secondly we will review the main angiogenic clinical trials, which will also be commented regarding their effectiveness to reduce the recurrency of angina symptoms and improve health-related quality-of-life, as well as the functional class of patients with chronic ischemic disease.

BACKGROUND: Surrogates of aortic wave reflection and arterial stiffness, such as augmentation index (AIx), augmentation pressure, pulse wave velocity (PWV) and pulse pressure amplification (PPampl) are independent predictors of cardiovascular risk. A novel ambulatory, brachial cuff-based oscillometric device has been recently developed and validated, yielding 24-h assessment of the aforementioned parameters (Mobilo-O-Graph). Aim of this study was to investigate the feasibility and reproducibility of wave reflection and arterial stiffness estimation by pulse wave analysis using this device. METHODS: Thirty treated or untreated hypertensives (mean age: 53.6 ± 11.6 years, 17 men) had test-retest 24-h monitoring one week apart using the test device. RESULTS: Mean numbers of valid aortic readings per subject, between test and retest, were comparable. Approximately 12 aortic readings per subject (17%) were not feasible or valid. No differences were observed for any 24-h parameter between the two assessments. Bland-Altman plots showed no systemic difference, while the limits of agreement for each parameter indicated high reproducibility (AIx: -7.2 to 8.2%, AP: -3.7 to 4.1mm Hg, PWV: -0.39 to 0.41 m/s, PPampl: -0.08 to 0.06). This was further verified by intraclass correlation coefficients which were >0.8 for each parameter. CONCLUSIONS: Non-invasive 24-h estimation of wave reflection and arterial stiffness indices, derived by the test device, appear to be highly reproducible. Future studies should investigate whether these measurements have additive prognostic value for cardiovascular risk stratification, beyond common brachial blood pressure measurements or single estimations of wave reflection and PWV at office settings.

BACKGROUND: Percutaneous approach techniques with closure device after transcatheter aortic valve implantation (TAVI) have diminished vascular complications (VC). In this retrospective study, we will report incidence and angiographic factors predisposing to major VC in patients undergoing TAVI using Prostar® XL closure device as a default strategy. METHODS: Consecutive patients, who underwent TAVI transfemorally using Prostar® XL, were evaluated for the incidence of VC according to VARC criteria. Using arterial angiography, the femoral-iliac arterial tortuosity was adjusted for large arterial diameters and expressed as the ratio total tortuosity/arterial diameter (TT/AD). Arterial calcification, the combination of angulation and atheromatosis at the puncture site and ideal puncture were evaluated too. In all patients, 30 days of follow-up was available. RESULTS: Eighty-four patients (80.2 ± 5.86 years, 39 males [46.4%]), who were consecutively treated with the transfemoral approach, were evaluated. In patients with major VC (17/84 [20.23%]) comparing to those without, arterial calcification (11 [64.7%] vs. 8 [11.9%], P < 0.01) and the TT/AD (30.2 ± 11.25 vs. 22.06 ± 8.64, P < 0.01) were independent predictors. Ideal puncture was achieved more frequently among patients without VC comparing to those with major (94.1% vs. 70.6%, P = 0.01). Blood transfusions (1.48 ± 0.37 vs. 2.45 ± 0.59, P = 0.023) were more frequent among patients with major VC. Finally, minimum creatinin clearance after TAVI predicted all-cause 30-day mortality (P = 0.021). CONCLUSIONS: Major VC after TAVI with the use of Prostar closure device can be predicted by arterial calcification at the puncture site and TT/AD ratio. Minimum creatinin clearance after TAVI predicted 30-day mortality.

OBJECTIVES: This study sought to investigate whether the site of common femoral artery (CFA) cannulation in regard to the inferior epigastric artery (IEA) is associated with the incidence of vascular complications in patients undergoing transfemoral aortic valve implantation (TAVI). BACKGROUND: Vascular access complications are a main issue during TAVI and have been associated with significant increase of morbidity and mortality. The need for establishment of reliable predictors for these serious events remains important. METHODS: A total of 90 patients, who had undergone TAVI, were retrospectively studied. Vascular complications were defined as major and minor according to the Valve Academic Research Consortium (VARC) criteria. Patients were divided into high cannulation site (CS) group and low CS group depending on the common femoral artery puncture site position, in regards to the most inferior border of the IEA. RESULTS: Vascular complications were significantly more frequent in the high CS group versus the low CS group (32.3% vs. 11.9%, P = 0.039). High cannulation remained an independent predictor of vascular complications after adjustment for known risk factors (OR: 4.827, CI: 1.441-16.168; P = 0.011). CONCLUSIONS: In patients undergoing transfemoral TAVI, arterial puncture above the most inferior border of the IEA is associated with vascular complications.

BACKGROUND: Intraplaque neovascularization and vasa vasorum (VV) proliferation contribute in the progression and rupture of atherosclerotic lesions. Contrast enhanced ultrasonography (CEUS) has been reported to attain data regarding intraplaque neovessels and VV. However, whether the detection of microbubbles by CEUS within atherosclerotic plaques truly represents microvessels is a point of concern. We aimed to evaluate stable and unstable carotid artery plaque (CAP) VV pattern by CEUS and its correlation with histology and immunochemistry. PATIENTS AND METHODS: Patients with CAP scheduled for plaque endarterectomy were enrolled. CAP was initially identified by conventional ultrasonography and subsequently CEUS (harmonic ultrasound imaging with simultaneous intravenous contrast agent injection) was performed. The recorded image loops were evaluated by a semi-automated method. Plaque specimens were excised and underwent histological and immunochemical (for CD34, Vascular Endothelial Growth Factor, CD68 and CD3 antibodies) analysis. RESULTS: Fourteen patients (67.6 ± 10.2 years, 10 males) with a 86.9 ± 11.5 % degree of carotid artery stenosis were evaluated. Histology showed that half of the plaques were unstable. Enhancement of plaque brightness on CEUS was significant for both stable and unstable plaque subgroups (p = 0.018 for both). Immunochemistry showed that microvessels, as assessed by CD34 antibody, were more dense in unstable vs. stable plaques (36.6 ± 17.4 vs. 13.0 ± 7.2 respectively, p = 0.002). However, correlation between plaque brigthness enhancement on CEUS and microvessel density was significant only for stable (r = 0.800, p = 0.031) plaques. CONCLUSIONS: The identification of brightness enhacement during CEUS in carotid atherosclerotic plaques may not always reflect the presence of VV.

BACKGROUND: We describe a vascular closure technique, convenient in practice, that permits effective femoral artery closure after CoreValve (Medtronic) implantation during transcatheter aortic valve implantation (TAVI). Vascular complications of transfemoral access implantation have been associated with significantly increased patient morbidity and mortality, as well as with increased hospitalization, among patients undergoing TAVI. TECHNIQUE: The crossover technique is performed while using the sheath dilatator in order to tightly grasp the crossover wire; a peripheral artery balloon is inserted in the iliac artery and inflated above the puncture site. The 18 Fr sheath is removed while hemostasis is achieved in that way. Minor vascular complications were observed in 10% (3 out of 30) of the patients treated with this vascular closure technique. No major vascular complications were observed. CONCLUSIONS: The described vascular closure maneuver is operator friendly, without demanding special skills and can be added to the therapeutic quiver for minimizing vascular complications after TAVI.

BACKGROUND: The influence of atrial septal occluders in left atrial (LA) function after percutaneous closure of patent foramen ovale (PFO) has not been thoroughly studied. METHODS: Twenty-five patients (mean age 40.7 ± 12 years) undergoing percutaneous PFO closure were enrolled in this study. Transthoracic echocardiogram (TTE) was performed 3 and 6 months before the procedure. Volumetric indices (active emptying fraction: LA AEF, expansion index: LA EI, and passive emptying fraction: LA PEF), strain and strain rate (SR), were calculated during the contractile, reservoir, and conduit LA phases for the lateral, anterior, and inferior LA walls with TTE. RESULTS: After 3 months, a decrease in the SR of the LA anterior wall was observed (from 2.12 ± 0.22 to 1.66 ± 0.26, P < 0.045), while the LA lateral wall strain was found to be increased (from 0.708 ± 0.15 to 0.783 ± 0.159, P < 0.001). Moreover, simultaneously LA AEF was greater compared with baseline (from 31.0 ± 1.6 to 34.0 ± 1.6, P < 0.004). However, all these alterations reversed at 6 months. CONCLUSIONS: Segmental LA function is altered transiently after percutaneous PFO closure with a septal occlude. The LA anterior wall SR decreases, while the lateral wall strain increases. The impact of these alterations needs further clarification.

Transcatheter aortic valve implantation (TAVI) is an emerging technology used to treat high-risk patients with severe aortic stenosis. During TAVI with the CoreValve ReValving System, a balloon is used for the reduction of paravalvular regurgitation. However, in this paper, we describe the "balloon withdrawal" technique through which the positioning of a second valve can be avoided in case of initial malpositioning. The result of the technique was rather encouraging, and minimal paravalvular aortic regurgitation was recorded after echocardiographic assessment.

MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides which act as down regulators of gene expression in the post-transcription level and/or in the translation level. Several studies have shown that the process of their maturation is rather crucial for the development of cardiovascular system thus their regulation (up-,down-) is implicated with many cardiac pathologies. This is evaluated through their circulating levels which are reliable, stable and the changes in their serum profiles are representative of tissue alterations serum levels. Furthermore, they have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure cardiac arrhythmias and aortic stenosis. In the present review, we will first describe i) the process of miRNAs' maturation ii) their role in the cardiovascular development, iii) their role as biomarkers of cardiac diseases, iv) the cardiac myo-miR families and the v) their role in cardiac remodeling and the development of cardiac diseases. Second we will review the miRNA families that participate in aortic stenosis separated according to its main pathways (imflammation, fibrosis, calcification). Finally, we will describe the miRNAs that participate in the development of aortic aneurysm and aortic dissection according to their serum levels.

BACKGROUND: The elastic properties of the ascending aorta were studied before and 1 week after transcatheter aortic valve implantation (TAVI). Previous studies have shown that the distensibility of the ascending aorta was decreased in the early post-operative period after aortic valve replacement. Aortic stiffness is a major moderator of arterio-ventricular coupling and an independent predictor of cardiovascular risk and mortality. We evaluated the effect of TAVI on the elastic properties of the ascending aorta in the early post-operative period. METHODS: Aortic distensibility (AD) and Aortic Stiffness Index (ASI) were evaluated using echocardiographic techniques and brachial artery pressure obtained by sphygmomanometry 2-3 days before and 7-8 days after TAVI. RESULTS: A total of 30 patients (14 males) were studied with a mean age of 79.9 ± 4.7 years and aortic valve area before TAVI of 0.61 ± 0.16 cm(2). Mean arterial pressure decreased significantly after TAVI (from 89.6 ± 8.9 mmHg to 83.3 ± 10.9 mmHg, p = 0.004). AD did not change significantly after TAVI (pre: 1.89 ± 1.11 cm(2)/(dynes × 10(6)), post: 2.05 ± 1.50 cm(2)/(dynes × 10(6)); p = 0.813). ASI also remained unchanged (pre: 11.4 ± 6.5, post: 15.6 ± 14.9; p = 0.349). CONCLUSIONS: The elastic properties of the ascending aorta did not change significantly in the early post-procedural period after TAVI. This may in part be attributable to the less invasive procedure (compared to aortic valve replacement) which has no effect on vasa vasorum flow.

BACKGROUND: Accumulating evidence suggests the potential superiority of office aortic blood pressure (BP) over brachial in the management of arterial hypertension. The noninvasive aortic 24-h ambulatory brachial BP monitoring (ABPM) is potentially the optimal method for assessing BP profile. The objective of the present study was to investigate the feasibility and reproducibility to perform noninvasively 24-h aortic ABPM with a novel validated brachial cuff-based automatic oscillometric device (Mobilo-O-Graph) which records brachial BP and waveforms and assesses aortic BP via mathematical transformation. METHODS: Thirty consecutive subjects (mean age: 53.6 ± 11.6 years, 17 men) had a test-retest ABPM with at least 1-week interval. No modification of vasoactive drug treatment during the interval was allowed while similar 24-h activity during both recording days was recommended. RESULTS: The average number of valid readings for brachial vs. aortic BP were 69.9 ± 10.4 vs. 58.0 ± 13.3 in the initial 24-h assessment (P < 0.001) and 68.3 ± 10.8 vs. 56.4 ± 13.6 in the repeat assessment (P < 0.001). No differences in average 24 h aortic BP values were observed between the two assessments (systolic blood pressure (SBP) 115.9 ± 7.7 vs. 115.1 ± 6.0 mm Hg, respectively, P = 0.48, and diastolic 79.7 ± 7.4 vs. 79.2 ± 8.7, P = 0.54). Reproducibility indices of aortic pressure including, intraclass coefficient of variation (SBP: 0.80 (95% confidence interval 0.58-0.90); diastolic: 0.92 (0.83-0.96)) and s.d. of differences (SBP/diastolic: 6.0/4.5 mm Hg) indicated acceptable reproducibility. The Bland-Altman plots indicated no evidence of systemic bias. CONCLUSIONS: In conclusion, these data suggest that noninvasive 24-h ABPM is feasible and provides reproducible values. Future studies should validate the prognostic ability of 24-h aortic hemodynamics.

There is increasing interest in utilizing novel markers of cardiovascular disease risk and consequently, there is a need to assess the value of their use. In this paper, we will review the role of biomarkers in acute coronary syndromes, heart failure and risk stratification for cardiovascular events as guide for treatment scribing. In particular, high sensitivity assays for troponin evaluation detect with greater precision patients with elevated troponin. Therefore, direct and appropriate management is succeeded in these patients with reduction of complications due to earlier treatment, as well. Regarding heart failure, randomized trials that have evaluated biomarker guided treatment approach have not succeeded in establishing specific results for natriuretic peptides (BNP, NT-proBNP) use in terms of therapy guidance. Apart from them, a variety of novel or already used biomarkers, have been tested by small trials for heart failure management, without however, managing to dominate in every day care. Finally, as far as risk stratification for cardiovascular events is concerned, hsCRP has proved to be a strong but doubted biomarker. Therefore, lifestyle and behavioral modification remain the cornerstone of primary prevention.

We report a case of an 84-year-old female with symptomatic severe aortic stenosis, who was treated with trans-catheter aortic-valve implantation (TAVI), through the left subclavian artery. A CoreValve bioprosthesis was successfully implanted, but the procedure was complicated by a focal left subclavian dissection and transient left-arm paralysis, which was successfully managed.

BACKGROUND: Residual platelet reactivity (RPR) after clopidogrel loading, measured by the VerifyNow assay, has been shown to predict 12-month clinical events in patients with acute coronary syndromes. However, links between coronary angiographic findings and outcome in patients with ST-elevation myocardial infarction (STEMI), with RPR have not been reported. We investigated whether RPR is associated with the amount of intracoronary thrombus burden (TB) in patients with STEMI undergoing unexpectedly-delayed primary percutaneous coronary intervention (pPCI). Moreover, we evaluated whether RPR might influence coronary flow and myocardial perfusion immediately post-pPCI. METHODS AND RESULTS: The VerifyNow assay was used to determine RPR after clopidogrel loading, expressed in P2Y12-Reaction-Units (PRU). Intracoronary-TB was angiographically estimated and stratified as TB-Grade-A, -B and -C. Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush (MB) were also estimated post-PCI. A total of 74 consecutive patients who presented with STEMI were enrolled in the study. Patients with greater TB presented significantly higher PRU-levels (174.1 ± 91.5, 196.23 ± 113.4 and 252.8 ± 107.8 for TB-Grade A, B and C, respectively; P=0.044). PRU-levels >251.5 were shown to predict Large-TB (LTB; TB-Grade-C) (sensitivity=57.9%; specificity=77.8%; P=0.014). Impaired TIMI-flow and MB after PCI were significantly associated with higher PRU-levels (P < 0.001). CONCLUSIONS: Among the studied patients, those with a higher RPR after clopidogrel loading presented larger intracoronary TB, worse post-PCI myocardial flow and perfusion.

Two techniques for correcting malpositioning occurring during percutaneous aortic valve replacement (PAVR) with the CoreValve ReValving™ System are described in this article. The "Removing and Reinserting Technique" was used in 2 patients, in whom the prosthesis was positioned too high. The "Snare Technique" was used in 1 patient, in whom the prosthesis was implanted too low. In all patients the aortic valve prosthesis was successfully re-implanted.

INTRODUCTION: transcatheter aortic valve implantation (TAVI) is an emerging technique for the treatment of aortic stenosis. With the advent of percutaneous suture devices for the access point and prosthesis delivery systems of smaller diameter, TAVI has become a truly percutaneous procedure: percutaneous aortic valve replacement (PAVR). Thus, PAVR may be conducted without general anaesthesia (GA). METHODS: We report two centres' experience from PAVR without GA. CoreValve aortic bioprostheses were utilised. The patient selection process and PAVR procedure are described in detail. RESULTS: a total of 30 patients (pts) were treated with PAVR. In 4 pts correction of the initial malposition of the prosthesis required a special technique (2 pts: "snare"; 2 pts: "removing and reinserting"). At 1-month follow up, haemodynamic and clinical improvements were observed: left ventricular ejection fraction increased from 50.8 ± 9.3% to 54.3 ± 8.3% (p=0.02); peak aortic valve gradient decreased from 90.3 ± 26.4 mmHg to 14.8 ± 9.7 mmHg, (p<0.001); NYHA functional class decreased from 3.53 ± 0.93 to 1.45 ± 0.94 (p<0.001). Overall 1-month mortality was 3.3% (1 patient died). CONCLUSION: PAVR without general anaesthesia is a feasible technique, however the role of anaesthesiologists is still important.

Severe aortic valve stenosis may be tackled with percutaneous aortic valve replacement instead of surgical replacement. At present, two CE marked prosthetic valves are available. The CoreValve ReValving System is primarily designed to be introduced transfemorally, while implantation via subclavian arteries has been described in cases of unsuitable femoral access. However, this route has been used when subclavian artery is free of disease. In this case report we describe a successful CoreValve ReValving System implantation via a diseased and tortuous left subclavian artery after predilatation balloon angioplasty. The prosthesis was then advanced in the native aortic valve, deployed, and successfully implanted. Techniques and manipulations are provided.