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The arrhythmogenic potential of alcohol consumption that leads to cardiac arrhythmia development includes the induction of both atrial and ventricular arrhythmias, with atrial fibrillation (AF) being the commonest alcohol-related arrhythmia, even with low/moderate alcohol consumption. Arrhythmias occur both with acute and chronic alcohol use. The "Holiday Heart Syndrome" relates to the occurrence of AF, most commonly following weekend or public holiday binge drinking; however, other arrhythmias may also occur, including other supraventricular arrhythmias, and occasionally even frequent ventricular premature beats and a rare occurrence of ventricular tachycardia. Arrhythmias in individuals with alcohol use disorder, in addition to AF, may comprise ventricular arrhythmias (VAs) that may be potentially fatal leading to cardiac arrest. The effects of alcohol on triggering VAs appear to be dose-dependent, observed more commonly in heavy drinkers, both in healthy individuals and patients with underlying structural heart disease, including ischemic heart disease and alcoholic cardiomyopathy. Men appear to be affected at higher dosages of alcohol, while women can suffer from arrhythmias at lower dosages. On the other hand, low to moderate consumption of alcohol may confer some protection from serious VAs and cardiac arrest (J- or U-curve phenomenon); however, abstinence is the optimal strategy. These issues as they relate to alcohol-induced proarrhythmia are herein reviewed, with the large studies and meta-analyses tabulated and the arrhythmogenic mechanisms pictorially illustrated.

Lipoprotein(a) or lipoprotein "little a" is an under-recognized causal risk factor for cardiovascular (CV) disease (CVD), including coronary atherosclerosis, aortic valvular stenosis, ischemic stroke, heart failure and peripheral arterial disease. Elevated plasma Lp(a) (≥50 mg/dL or ≥100 nmol/L) is commonly encountered in almost 1 in 5 individuals and confers a higher CV risk compared to those with normal Lp(a) levels, although such normal levels have not been generally agreed upon. Elevated Lp(a) is considered a cause of premature and accelerated atherosclerotic CVD. Thus, in patients with a positive family or personal history of premature coronary artery disease (CAD), Lp(a) should be measured. However, elevated Lp(a) may confer increased risk for incident CAD even in the absence of a family history of CAD, and even in those who have guideline-lowered LDL-cholesterol (

Cilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its "pleiotropic" effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta-analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated.

Cardiac resynchronization therapy (CRT) has been established as an effective mode of therapy in patients with heart failure and concurrent cardiac dyssynchrony, principally in the form of left bundle branch block (LBBB). The widespread use of CRT has ushered in a new landscape in 12-lead electrocardiography (ECG). ECG readings in these patients are most important to guide troubleshooting and also appropriate device programming, as well as discerning and managing nonresponders. A set of four ECG recordings need to accompany each patient with a CRT device, including a baseline ECG and recordings from monochamber (right and left ventricular) and biventricular pacing, which can be compared against a new recording to facilitate the evaluation of proper versus problematic biventricular pacing. Precordial ECG leads V1/2 acquired at the fourth intercostal space and limb leads, I and III, together with a quick assessment of perpendicular leads I and aVF to determine the quadrant of the QRS axis in the hexaxial diagram, may provide the framework for proper ECG interpretation in these patients. This important issue of 12-lead ECG in CRT patients is herein reviewed, pitfalls are pointed out and practical tips are provided for ECG reading to help recognize and manage problems with CRT device function. Furthermore, several pertinent ECG recordings and tabulated data are provided, and an algorithm is suggested that integrates prior algorithms and relevant information from current literature.

As a potentially life-threatening disease with no definitive treatment and without fully implemented population-wide vaccination, COVID-19 has created unprecedented turmoil in socioeconomic life worldwide. In addition to physical signs from the respiratory and many other systems, the SARS-CoV-2 virus produces a broad range of neurological and neuropsychiatric problems, including olfactory and gustatory impairments, encephalopathy and delirium, stroke and neuromuscular complications, stress reactions, and psychoses. Moreover, the psychosocial impact of the pandemic and its indirect effects on neuropsychiatric health in noninfected individuals in the general public and among health care workers are similarly far-ranging. In addition to acute neuropsychiatric manifestations, COVID-19 may also produce late neuropsychiatric sequelae as a function of the psychoneuroimmunological cascade that it provokes. The present article presents a state-of-the-science review of these issues through an integrative review and synthesis of case series, large-cohort studies, and relevant meta-analyses. Heuristics for evaluation and further study of the neuropsychiatric manifestations of SARS-CoV-2 infection are offered.

Introduction After mitral isthmus (ΜΙ) catheter ablation, perimitral atrial flutter (PMF) circuits can be maintained due to the preservation of residual myocardial connections, even if conventional pacing criteria for complete MI block are apparently met (MI pseudo‐block). We aimed to study the incidence, the electrophysiological characteristics, and the long‐term outcome of these patients. Methods Seventy‐two consecutive patients (mean age 62.4 ± 10.2, 62.5% male) underwent MI ablation, either as part of an atrial fibrillation (AF) ablation strategy (n = 35), or to treat clinical reentrant atrial tachycardia (AT) (n = 32), or to treat AT that occurred during ablation for AF (n = 5). Ιn all patients, the electrophysiological characteristics of PMF circuits were studied by high‐density mapping. Results Mitral isthmus block was successfully achieved in 69/72 patients (95.6%). Five patients developed PMF after confirming MI block. In these patients, high‐density mapping during the PMF showed a breakthrough in MI with extremely low impulse conduction velocity (CV). In contrast, in usual PMF circuits that occurred after AF ablation, the lowest CV of the reentrant circuit was of significantly higher value (0.07 ± 0.02 m/s vs 0.25 ± 0.07 m/s, respectively; P, This is a retrospective clinical study comprising 72 patients who underwent mitral isthmus (MI) ablation either as part of an atrial fibrillation ablation strategy, or to treat reentrant AT. The MI block was acutely achieved in 69/72 patients. However, five patients, despite showing MI block based on conventional pacing maneuvers, developed perimitral atrial flutter through a gap in previous ablation lesions with extremely low impulse conduction velocity as shown by high density mapping.

Objective In 2008, the radiofrequency ablation (RFA) procedures registry of the Hellenic Society of Cardiology was created. This online database allowed electrophysiologists around the country to input data for all performed ablation procedures. The aim of this study is to provide a thorough report and interpretation of the data submitted to the registry between 2008 and 2018. Methods In 2008, a total of 27 centers/medical teams in 24 hospitals were licensed to perform RFA in Greece. By 2018, the number had risen to 31. Each center was tasked with inserting their own data into the registry, which included patient demographics (anonymized), type of procedure and technique, complications, and outcomes. Results A total of 18587 procedures in 17900 patients were recorded in the period of 2008-2018. By 2018, slightly more than 70% of procedures were performed in 7 high-volume centers (>100 cases/year). The most common procedure since 2014 was atrial fibrillation ablation, followed by atrioventricular nodal reentry tachycardia ablation. Complication rates were low, and success rates remained high, whereas the 6-month relapse rates declined steadily. Conclusion This online RFA registry has proved that ablation procedures in Greece have reached a very high standard, with results and complication rates comparable to European and American standards. Ablation procedures for atrial fibrillation are increasing constantly, with it being the most common intervention over the last 6-year period, although the absolute number of procedures still remains low, compared to other European countries.

Sleep is essential to and an integral part of life and when lacking or disrupted, a multitude of mental and physical pathologies ensue, including cardiovascular (CV) disease, which increases health care costs. Several prospective studies and meta-analyses show that insomnia, short (9h) sleep and other sleep disorders are associated with an increased risk of hypertension, metabolic syndrome, myocardial infarction, heart failure, arrhythmias, CV disease risk and/or mortality. The mechanisms by which insomnia and other sleep disorders lead to increased CV risk may encompass inflammatory, immunological, neuro-autonomic, endocrinological, genetic and microbiome perturbations. Guidelines are emerging that recommend a target of >7 h of sleep for all adults >18 years for optimal CV health. Treatment of sleep disorders includes cognitive-behavioral therapy considered the mainstay of non-pharmacologic management of chronic insomnia, and drug treatment with benzodiazepine receptor agonists binding to gamma aminobutyric acid type A (benzodiazepine and non-benzodiazepine agents) and some antidepressants. However, observational studies and meta-analyses indicate an increased mortality risk of anxiolytics and hypnotics, although bias may be involved due to confounding and high heterogeneity in these studies. Nevertheless, it seems that the risk incurred by the non-benzodiazepine hypnotic agents (Z drugs) may be relatively less than the risk of anxiolytics, with evidence indicating that at least one of these agents, zolpidem, may even confer a lower risk of mortality in adjusted models. All these issues are herein reviewed.

PURPOSE OF REVIEW: The new pandemic of coronavirus disease-2019 (COVID-19) has produced a global tumult and has overburdened national health systems. We herein discuss the cardiovascular implications and complications of this pandemic analyzing the most recent data clustered over the last several months. RECENT FINDINGS: COVID-19 afflicts the cardiovascular system producing acute cardiac injury in 10-20% of cases with mild disease but in greater than 50-60% in severe cases, contributing to patients' demise. Other cardiovascular complications include arrhythmias, heart failure, pulmonary embolism and shock. Off-label therapies are being trialed with their own inherent cardiovascular risks, while supportive therapies currently dominate, until more specific and effective antiviral therapies and vaccinations become available. A controversial issue relates to the safety of drugs blocking the renin--angiotensin system as an angiotensin-converting enzyme (ACE) homologue, ACE2, serves as the receptor for viral entry into host cells. However, to-date, no harm has been proven for these drugs. SUMMARY: In the cardiovascular system, COVID-19 can induce acute cardiac injury, arrhythmias, heart failure, pulmonary embolism, shock and death, whereas anti-COVID therapies also confer serious cardiovascular side-effects. Ongoing extensive efforts focus on specific vaccines and antivirals. Meanwhile, cardiovascular risk factors and diseases should be jointly controlled according to current evidence-based guidelines.

Highlights • Serious cardiac arrhythmias may be the consequence of direct effects of COVID-19 infection, but also the outcome of the deleterious effects of systemic illness and the adverse proarrhythmic reactions to drugs employed in the treatment of this pandemic • Drug combinations, especially of QT-prolonging agents, can lead to higher arrhythmogenicity, compared with single drug therapies • Furthermore, critically ill COVID-19 patients often have comorbidities that can trigger life-threatening ventricular arrhythmias, while acute myocardial injury increases the prevalence of arrhythmias • ECG and QTc monitoring and taking appropriate measures are of critical importance to prevent, detect and manage cardiac arrhythmias in COVID-19 patients • Contactless monitoring and telemetry for inpatients, especially those admitted to the ICU, as well as for outpatients needing continued management, has recently been facilitated by implementing digital health monitoring tools, As the coronavirus 2019 (COVID-19) pandemic marches unrelentingly, more patients with cardiac arrhythmias are emerging due to the effects of the virus on the respiratory and cardiovascular (CV) systems and the systemic inflammation that it incurs, and also as a result of the proarrhythmic effects of COVID-19 pharmacotherapies and other drug interactions and the associated autonomic imbalance that enhance arrhythmogenicity. The most worrisome of all arrhythmogenic mechanisms is the QT prolonging effect of various anti-COVID pharmacotherapies that can lead to polymorphic ventricular tachycardia in the form of torsade des pointes and sudden cardiac death. It is therefore imperative to monitor the QT interval during treatment; however, conventional approaches to such monitoring increase the transmission risk for the staff and strain the health system. Hence, there is dire need for contactless monitoring and telemetry for inpatients, especially those admitted to the intensive care unit, as well as for outpatients needing continued management. In this context, recent technological advances have ushered in a new era in implementing digital health monitoring tools that circumvent these obstacles. All these issues are herein discussed and a large body of recent relevant data are reviewed.

Objective: Vitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF. Methods: One hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group. Results: A total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p

Myocardial infarction with non-obstructive coronary arteries or any acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACS-NNOCA) is an heterogeneous clinical entity, which includes different pathophysiology mechanisms and is challenging to treat. Sudden cardiac death (SCD) is a catastrophic manifestation of ACS that is crucial to prevent and treat urgently. The concurrence of the two conditions has not been adequately studied. This narrative review focuses on the existing literature concerning ACS-NNOCA pathophysiology, with an emphasis on SCD, together with risk and outcome data from clinical trials. There have been no large-scale studies to investigate the incidence of SCD within ACS-NNOCA patients, both early and late in the disease. Some pathophysiology mechanisms that are known to mediate ACS-NNOCA, such as atheromatous plaque erosion, anomalous coronary arteries, and spontaneous coronary artery dissection are documented causes of SCD. Myocardial ischaemia, inflammation, and fibrosis are probably at the core of the SCD risk in these patients. Effective treatments to reduce the relevant risk are still under research. ACS-NNOCA is generally considered as an ACS with more ‘benign’ outcome compared to ACS with obstructive coronary artery disease, but its relationship with SCD remains obscure, especially until its incidence and effective treatment are evaluated.

Patients with rheumatoid diseases have an increased risk of cardiovascular disease (CVD) and CVD-related death compared with the general population. Both the traditional cardiovascular risk factors and systemic inflammation are contributors to this phenomenon. This review examines the available evidence about the effects of synthetic, non-biologic disease-modifying antirheumatic drugs (DMARDs) on CVD risk. This is an important issue for clinicians when deciding on individual treatment plans in patients with rheumatic diseases. Evidence suggests that synthetic, non-biologic DMARDs such as methotrexate, sulfasalazine, hydroxychloroquine, leflunomide and tofacitinib show decreased CVD morbidity and mortality. However, the strongest data in favour of a reduction in CVD events in rheumatoid patients are shown with methotrexate, which has been the focus of most studies. Adequate proof for a favourable effect also exists for hydroxychloroquine. Larger, prospective studies and randomized clinical trials are needed to better characterize the effect of synthetic, non-biologic DMARDs on CVD outcomes in these patients. Design of future studies should include areas with lack of evidence, such as the risk for heart failure, arrhythmias and valvular heart disease. The clinically relevant question whether synthetic, non-biologic DMARDs are inferior to biologic DMARDs in terms of CVD outcomes remains not adequately addressed.

Congenital complete heart block (CCHB) occurs in 2-5% of pregnancies with positive anti-Ro/SSA and/or anti-La/SSB antibodies, and has a recurrence rate of 12-25% in a subsequent pregnancy. After trans-placental passage, these autoantibodies attack and destroy the atrioventricular (AV) node in susceptible fetuses with the highest-risk period observed between 16 and 28 weeks' gestational age. Many mothers are asymptomatic carriers, while

Cardiac arrhythmias are the most common cardiac complication reported in pregnant women with and without structural heart disease (SHD); they are more frequent among women with SHD, such as cardiomyopathy and congenital heart disease (CHD). While older studies had indicated supraventricular tachycardia as the most common tachyarrhythmia in pregnancy, more recent data indicate an increase in the frequency of arrhythmias, with atrial fibrillation (AF) emerging as the most frequent arrhythmia in pregnancy, attributed to an increase in maternal age, cardiovascular risk factors and CHD in pregnancy. Importantly, the presence of any tachyarrhythmia during pregnancy may be associated with adverse maternal and fetal outcomes, including death. Thus, both the mother and the offspring need to be protected from such consequences. The use of antiarrhythmic drugs (AADs) depends on clinical presentation and on the presence of underlying SHD, which requires caution as it promotes pro-arrhythmia. In hemodynamically compromised women, electrical cardioversion is successful and safe to both mother and fetus. Use of beta-blockers appears quite safe; however, caution is advised when using other AADs, while no AAD should be used, if at all possible, during the first trimester when organogenesis takes place. Regarding the anticoagulation regimen in patients with AF, warfarin should be substituted with heparin during the first trimester, while direct oral anticoagulants are not indicated given the lack of data in pregnancy. Finally, for refractory arrhythmias, ablation and/or device implantation can be performed with current techniques in pregnant women, when needed, using minimal exposure to radiation. All these issues and relevant current guidelines are herein reviewed.

Growing evidence suggests that atrial fibrillation (AF), in addition to its thromboembolic risk, is a risk factor for cognitive impairment (CI) via several pathways and mechanisms, further contributing to morbidity/mortality. Prior stroke is a contributor to CI, but AF is also associated with CI independently from prior stroke. Silent brain infarctions, microemboli and microbleeds, brain atrophy, cerebral hypoperfusion from widely fluctuating ventricular rates, altered hemostatic function, vascular oxidative stress, and inflammation may all exacerbate CI, particularly in patients with persistent/permanent rather than paroxysmal AF and with increased duration/burden of the arrhythmia. Brain magnetic resonance imaging is an important screening tool in eliciting and monitoring vascular and nonvascular lesions contributing to CI. Evidence is also emerging about the role of genetics in CI development. Anticoagulation and rhythm/rate control strategies may protect against CI preventing or slowing its progression or conversion to dementia, particularly at the early stages when CI may still be a treatable condition. Importantly, AF and CI share many common risk factors. Thus, screening for these 2 conditions and searching for and managing modifiable risk factors and potentially reversible causes for both AF and CI remains an important step toward prevention or amelioration of the impact incurred by these 2 conditions.

Subclinical thyroid dysfunction (STD), presenting as subclinical hypothyroidism (SHypo) or subclinical hyperthyroidism (SHyper), defined as abnormal serum thyrotropin (TSH) and normal free thyroid hormones, is associated with increased cardiovascular (CV) risk and mortality. Depending on the degree of such dysfunction, atherosclerosis, coronary artery disease, heart failure and cardiac arrhythmias, predominantly atrial fibrillation, characterize both disorders and increase CV and total mortality compared to euthyroid persons. There are some differences in the mechanisms involved in the increased CV risk incurred by each type of STD, with more traditional CV risk factors clustered in SHypo than in SHyper, while the role of the TSH or its absence thereof, together with the respective, even subtle, changes incurred in thyroid hormone concentrations, seem to adversely influence the CV system in both types of STD. There is evidence that treatment of STD confers potential benefits by reducing CV events, however, no consensus has been reached due to lack of randomized controlled studies. Nevertheless, due to accumulating evidence from observational studies, many authorities agree that individuals with severe SHypo (TSH 10 mIU/L) or grade 2 SHyper (TSH 0.1 mIU/L) should receive treatment, mostly for the increased risk of CV morbidity and mortality. The evidence reviewed herein should alert and help the clinician to wake up to these two potentially alarming conditions of STD as they may confer serious CV complications, while their treatment appears quite beneficial.

Proton pump inhibitors (PPIs) are among the most widely prescribed agents, either for treatment or prophylaxis of gastrointestinal (GI) disease, that are often administered for prolonged or chronic use. Patients with cardiovascular (CV) disease frequently receive PPIs for prophylaxis against GI bleeding due to common use of antithrombotic drugs. Over the last several years there is a growing number of reports associating chronic PPI use with a variety of serious CV and non-CV adverse effects. In this context, PPI use has been independently associated with an increased risk of CV morbidity (myocardial infarction, stroke, other CV events) and mortality. However, the critique remains that these data do not largely derive from randomized controlled trials. On the other hand, in certain conditions, the benefits of PPIs may outweigh the risks of adverse CV effects. As the indications for prolonged, particularly lifelong, prophylactic use of PPIs are not compelling and in the light of evidence of serious CV and other adverse effects, clinicians have to reconsider such long-term use of these drugs. Importantly, histamine 2 blockers have not been found to be associated with increased CV risk and thus may be an alternative therapeutic option in certain patients. These issues are amply discussed together with the potential mechanisms of these pleiotropic and off-target effects of PPIs, which are also depicted in an illustrative schema; data are also presented on differential effects of specific agents involved, alternative modes of therapy available, and relevant current guidelines on this issue.

Spironolactone, an antagonist of aldosterone, initially used as a potassium-sparing diuretic, was subsequently shown to be a very effective adjunctive agent in the treatment of patients with heart failure with reduced ejection fraction, by halting the disease progression, with significant beneficial effects on both morbidity and mortality. Other uses comprise resistant hypertension, edema in patients with cirrhosis, and other on- and off-label uses. Recent data indicate that spironolactone also may offer some symptomatic relief in patients with heart failure and preserved ejection fraction. However, a variable percentage of patients, particularly among the aged group, may have difficulty in swallowing or may be unable to swallow tablets and thus are deprived of the benefits of such therapy. In 2017, the FDA approved a liquid suspension formulation of spironolactone, CaroSpir®, which will enable more heart failure and other patients in need of aldosterone inhibition to avail themselves of the protective and beneficial effects of spironolactone. The new drug formulation comes as a banana-flavored oral suspension that contains 25 mg/5 mL of spironolactone, supplied in 4-ounce (118 mL) and 16-ounce (473 mL) bottles. The details of this drug formulation development and the benefits of spironolactone use in patients with heart failure with a focus on patient selection are herein reviewed.

Pulmonary vein (PV) isolation (PVI) remains cornerstone to ablation of atrial fibrillation (AF). For effective and durable PVI and thus fewer AF recurrences, lesion gaps in transmurality and contiguity responsible for PV reconnection (PVR) could only be addressed when one is cognizant of the potential location and sites where these lesion characteristics may be more prevalent and responsible for PVR. In the case of RF ablation, newer technologies incorporating contact force, time and power with automated monitoring of lesion formation, paying attention to difficult areas (carinae, left superior PV-LAA ridge, right inferior PV) and measuring inter-lesion distance may provide the tools to reduce PVR. On the other hand, the improved thermodynamic characteristics of the latest generation of cryoballloons and operator dexterity to achieve better PV occlusion, may be crucial determinants towards the direction of reduced PVR. Whether newer visualization tools, more vigilant testing during the index ablation procedure in these particular regions, prolonging or adding cryothermic applications, waiting longer to test for entrance and exit block, and/or use of provocative drug testing (isoproterenol/adenosine challenge) might help prevent future PVRs awaits further studies. Keywords: Atrial fibrillation, Catheter ablation, Radiofrequency ablation, Pulmonary veins, Pulmonary vein isolation, Pulmonary vein reconnection, Carina, Cryoballoon, Cryothermic ablation

Aims Per standard of care, dual-chamber pacemakers are programmed in DDDR mode with fixed atrioventricular (AV) delay or with long AV delay to minimize ventricular pacing. We aimed to evaluate whether the PR interval may be a specific criterion of choice between standard DDDR, to preserve AV synchrony in long PR patients, and managed ventricular pacing (MVP), to avoid ventricular desynchronization imposed by right ventricle apical pacing, in short PR patients. Methods and results In the MINERVA trial, 1166 patients were randomized to Control DDDR, MVP, or atrial anti-tachycardia pacing plus MVP (DDDRP + MVP). We evaluated the interaction of PR interval with pacing mode by comparing the risk of atrial fibrillation (AF) longer than 7 consecutive days as a function of PR interval. Out of 906 patients with available data, the median PR interval was 180 ms. The PR interval was found to significantly (P = 0.012) interact with pacing mode for AF incidence: the risk of AF > 7 days was lower [hazard ratio (HR) 0.58, 95% confidence interval (95% CI) 0.34-0.99; P = 0.047] in patients with short PR (shorter than median PR) if programmed in MVP mode compared with DDDR mode and it was lower (HR 0.65, 95% CI 0.43-0.99; P = 0.049) in patients with long PR (equal to or longer than median PR) if programmed in DDDR mode compared with MVP. Conclusion Our data show that PR interval may be used as a selection criterion to identify the optimal physiological pacing mode. Persistent AF incidence was lower in short PR patients treated by right ventricular pacing minimization and in long PR patients treated by standard dual-chamber pacing.

Background: Intracoronary thrombus in acute Myocardial Infarction (MI) confers higher rates of no-reflow with attendant adverse consequences. Earlier Randomized-Controlled-Trials (RCTs) of routine thromboaspiration during Percutaneous Coronary Intervention (PCI) indicated a clinical benefit, but more recent RCTs were negative. However, data of selective use of this adjunctive approach remain scarce. Objective: The aim of this single-centre prospective study was to report the results of selective thromboaspiration during PCI in patients with intracoronary thrombi, and also to provide an extensive literature review on current status of thromboaspiration. Methods: The study included 90 patients (77 men; aged 59.3±12.7 years) presenting with acute MI (STElevation MI (STEMI) in 74, non-STEMI in 16) who had intracoronary thrombi and were submitted to thromboaspiration. Results: Total (n=67) or subtotal (n=18) vessel occlusions were present in 85 (94%) patients. Thromboaspiration and subsequent PCI were successful in 89/90 (98.9%) patients, with coronary stenting in 86 (96.6%). In 4 patients with residual thrombus, a mesh-covered stent was implanted. IIb/IIIa-inhibitors were administered in 57 (63.3%) patients. No-reflow occurred in only 1 (1.1%) patient. The postprocedural course was uneventful. Review of the literature revealed several early observational and RCTs and meta-analyses favouring manual, not mechanical, thrombectomy. However, newer RCTs and meta-analyses significantly curtailed the initial enthusiasm for the clinical benefits of routine use of thromboaspiration. Conclusion: Selective thromboaspiration for angiographically visible thrombi in MI patients undergoing PCI, as an adjunct to mechanical reperfusion and to IIb/IIIa-inhibitors, may be an option since this manoeuvre may improve procedural and clinical outcome.

Radiofrequency catheter ablation (RFCA) of focal atrial tachycardia (FAT) traditionally is guided by conventional endocardial mapping of earliest atrial activation; however, more recently electro-anatomical mapping is heralded as a more effective, albeit more expensive, tool to guide ablation. Herein we present the results of conventional mapping-guided RFCA. Apropos, we conducted a literature search of studies reporting > 10 FAT patients submitted to RFCA. Conventional mapping-guided RFCA, performed in 63 FAT patients (aged 42.4 + 17.3 years; 14 with incessant tachycardia and 12 with tachycardiomyopathy (TCM)), was successful in 61 (96.8%) patients, applied for single foci in 59 (93.7%) and two foci in 4 patients, right (n = 46) or left sided (n = 17). The earliest atrial activation time at the ablation site was 41.3 ± 16.2 ms. Fluoroscopy time averaged 27.3 + 18.7 min, and procedure lasted 2.6 + 1.7 h. Complications occurred in two patients (sinus pauses in one needing a pacemaker and a large inguinal hematoma in one). Over 29.0 + 22.9 months, four patients (6.5%) had recurrences, of whom three were successfully re-ablated. All patients with TCM showed gradual improvement to normalization over 4–6 months. Literature search showed that RFCA success is equally high when guided with either conventional (88.5%) or electro-anatomical mapping (90%) with similar recurrences (9.6% vs. 9.5%). Conventional mapping-guided RFCA of FAT had high success (96.8%) with low complication (3.2%) and recurrence rates (6.5%). TCM was fully reversible. These results are comparable to those achieved with the more expensive electro-anatomical mapping, which may be reserved for more complex cases or for those failing the conventional approach.

In the era of the coronavirus disease 2019 (COVID-19) pandemic, acute cardiac injury (ACI), as reflected by elevated cardiac troponin above the 99th percentile, has been observed in 8%-62% of patients with COVID-19 infection with highest incidence and mortality recorded in patients with severe infection. Apart from the clinically and electrocardiographically discernible causes of ACI, such as acute myocardial infarction (MI), other cardiac causes need to be considered such as myocarditis, Takotsubo syndrome, and direct injury from COVID-19, together with noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis. Acute coronary syndromes (ACS) with normal or near-normal coronary arteries (ACS-NNOCA) appear to have a higher prevalence in both COVID-19 positive and negative patients in the pandemic compared to the pre-pandemic era. Echocardiography, coronary angiography, chest computed tomography and/or cardiac magnetic resonance imaging may render a correct diagnosis, obviating the need for endomyocardial biopsy. Importantly, a significant delay has been recorded in patients with ACS seeking advice for their symptoms, while their routine care has been sharply disrupted with fewer urgent coronary angiographies and/or primary percutaneous coronary interventions performed in the case of ST-elevation MI (STEMI) with an inappropriate shift toward thrombolysis, all contributing to a higher complication rate in these patients. Thus, new challenges have emerged in rendering a diagnosis and delivering treatment in patients with ACI/ACS in the pandemic era. These issues, the various mechanisms involved in the development of ACI/ACS, and relevant current guidelines are herein reviewed.

Coronavirus-2019 (COVID-19) predisposes patients to arterial and venous thrombosis commonly complicating the clinical course of hospitalized patients and attributed to the inflammatory state, endothelial dysfunction, platelet activation and blood stasis. This viral coagulopathy may occur despite thromboprophylaxis and raises mortality; the risk appears highest among critically ill inpatients monitored in the intensive care unit. The prevalence of venous thromboembolism in COVID-19 patients has been reported to reach ∼10-35%, while autopsies raise it to nearly 60%. The most common thrombotic complication is pulmonary embolism, which though may occur in the absence of a recognizable deep venous thrombosis and may be due to pulmonary arterial thrombosis rather than embolism, resulting in thrombotic occlusion of small- to mid-sized pulmonary arteries and subsequent infarction of lung parenchyma. This micro-thrombotic pattern seems more specific for COVID-19 and is associated with an intense immuno-inflammatory reaction that results in diffuse occlusive thrombotic micro-angiopathy with alveolar damage and vascular angiogenesis. Furthermore, thrombosis has also been observed in various arterial sites, including coronary, cerebral and peripheral arteries. Biomarkers related to coagulation, platelet activation and inflammation have been suggested as useful diagnostic and prognostic tools for COVID-19-associated coagulopathy; among them, D-dimer remains a key biomarker employed in clinical practice. Various medical societies have issued guidelines or consensus statements regarding thromboprophylaxis and treatment of these thrombotic complications specifically adapted to COVID-19 patients. All these issues are detailed in this review, data from meta-analyses and current guidelines are tabulated, while the relevant mechanisms of this virus-associated coagulopathy are pictorially illustrated.

In Part 1 of this Thematic Issue entitled “Systemic Autoimmune Rheumatic Diseases and Cardiology”, a panel of specialists and experts in cardiology, rheumatology, immunology and related fields discussed the cardiovascular complications of spondyloarthritides, rheumatoid arthritis, Sjogren’s syndrome and vasculitides, as well as relevant cardiovascular issues related to non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), and provided their recommendations for prevention and management of these complications. In part 2 of this Thematic Issue, experts discuss the enhanced cardiovascular risk conferred by additional autoimmune rheumatic diseases (ARDs), including systemic lupus erythematosus, the antiphospholipid syndrome, psoriasis and psoriatic arthritis and juvenile idiopathic arthritis. These, and the previous articles, place inflammation as the key common link to explain the enhanced risk of cardiovascular complications in patients with ARDs. It follows that treatment should probably target inflammation. From all these contemporary reviews, the conclusion that is derived further supports the notion of the emerging field of Cardio- Rheumatology where physicians and experts from these two disciplines collaborate in risk stratification and optimization of preventive strategies and drug therapies in patients with ARDs.

The autonomic nervous system (ANS) with its two limbs, the sympathetic (SNS) and parasympathetic nervous system (PSNS), plays a critical role in the modulation of cardiac arrhythmogenesis. It can be both pro- and/or anti-arrhythmic at both the atrial and ventricular level of the myocardium. Intricate mechanisms, different for specific cardiac arrhythmias, are involved in this modulatory process. More data are available for the arrhythmogenic effects of the SNS, which, when overactive, can trigger atrial and/or ventricular "adrenergic" arrhythmias in susceptible individuals (e.g. in patients with paroxysmal atrial fibrillation-PAF, ventricular pre-excitation, specific channelopathies, ischemic heart disease or cardiomyopathies), while it can also negate the protective anti-arrhythmic drug effects. However, there is also evidence that PSNS overactivity may be responsible for triggering "vagotonic" arrhythmias (e.g. PAF, Brugada syndrome, idiopathic ventricular fibrillation). Thus, a fine balance is necessary to attain in these two limbs of the ANS in order to maintain eurhythmia, which is a difficult task to accomplish. Over the years, in addition to classical drug therapies, where beta-blockers prevail, several ANS-modulating interventions have been developed aiming at prevention and management of arrhythmias. Among them, techniques of cardiac sympathetic denervation, renal denervation, vagal stimulation, ganglionated plexi ablation and the newer experimental method of optogenetics have been employed. However, in many arrhythmogenic diseases, ANS modulation is still an investigative tool. Initial data are encouraging; however, further studies are needed to explore the efficacy of such interventions. These issues are herein reviewed and old and recent literature data are discussed, tabulated and pictorially illustrated.

In the current Thematic Issue of Current Vascular Pharmacology (CVP), entitled “Systemic Autoimmune Rheumatic Diseases and Cardiology”, presented in two parts, Part 1 and Part 2, review articles are included from specialists in cardiology, rheumatology, immunology and related fields. These reviews discuss the cardiovascular complications of the main systemic Autoimmune Rheumatic Diseases (ARDs). For example, the underlying pathogenetic mechanisms, the role of cardiovascular imaging and recommendations for prevention and management. These articles place inflammation as the key process, linking cardiovascular complications with ARDs. From all these reviews, the conclusion is the need for collaboration between the disciplines of Rheumatology and Cardiology to establish the emerging field of Cardio- Rheumatology. This will aid to fine-tune risk stratification and optimize preventive strategies and pharmacological therapies for patients with ARDs.

Patients with acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) constitute an important, albeit heterogeneous, patient subset of younger patients, more commonly females, who may have lower risk of cardiovascular events compared to patients with obstructive coronary artery disease; however this risk remains substantial, hence needing further investigation to identify the underlying cause and devise a proper therapeutic strategy. A diagnostic algorithm starts during coronary angiography with some essential additional diagnostic steps, such as a left ventricular angiogram that may readily identify the underlying cause, e.g. Takotsubo syndrome, while intravascular imaging and vascular reactivity testing may need to be considered for assessing other diagnostic possibilities (e.g. occult atherosclerotic plaque rupture, spontaneous coronary dissection or microvascular dysfunction). Nevertheless, pursuing further investigation with less risky noninvasive tests, such as echocardiography and cardiac magnetic resonance imaging, may effectively identify the cause of ACSNNOCA (e.g. myocarditis or Takotsubo syndrome), and guide management.

Cardiac resynchronization therapy (CRT) is an established therapeutic option for the subset of patients with heart failure (HF), reduced ejection fraction (EF), and dyssynchrony evidenced by electrocardiography. Benefit from CRT has been proven in many clinical trials, yet a sizeable proportion of these patients with wide QRS do not respond to this intervention, despite the updated practice guidelines. Several echocardiographic indices, targeting mechanical rather than electrical dyssynchrony, have been suggested to address this issue, but research so far has not succeeded in providing a single and simple measurement with adequate sensitivity and specificity for identification of responders. While there is still ongoing research in this field, echocardiography proves helpful in other aspects of CRT implementation, such as site selection for left ventricular (LV) lead pacing and optimization of pacing parameters during follow-up visits. Keywords: Heart failure, cardiac resynchronization therapy, biventricular pacing, echocardiography

Results from recent cardiovascular outcome trials have ushered in a new era in the management of type 2 diabetes mellitus, moving from a focus on glycemic control to the cardiovascular safety of antihyperglycemic agents. Several new antihyperglycemic drugs have been shown to exert either neutral or cardioprotective effects in patients with diabetes. Among them, the sodium-glucose co-transporter-2 (SGLT-2) inhibitors (gliflozins) and selected agents from the incretin mimetics or enhancers, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins), appear to confer cardiovascular safety and/or protection in patients with underlying, or at high risk for, cardiovascular disease. Metformin remains the standard first-line drug treatment for patients with diabetes because of its established effectiveness and cardiovascular safety. However, this initial drug therapy may not prove adequate as this disease appears to be progressive with a decline in function of the pancreatic beta cells, necessitating the addition of other agents to better control rising glucose levels. With the advent of several new classes of antihyperglycemic drugs and the completion of their respective cardiovascular outcome trials, the therapeutic armamentarium against this disease pandemic appears to be greatly expanding and moving closer to the direction of the Hippocratic aphorism "Do Good or Do No Harm". In this review, we discuss all these issues and summarize the contemporary literature on cardiovascular safety and outcomes of the available glucose-lowering agents.

Patients with cancer are subject to the cardiotoxic effects of cancer therapy and as more patients survive cancer due to improved treatment they are exposed to various forms of cardiovascular (CV) disease as they age, and vice-versa. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.This two-part review considers the effects of cancer drug treatment on the CV system. In Part I, the various types of CV and cardiometabolic toxicity of anti-cancer drugs and the possible mechanisms involved are discussed. Also, among the specific oncologic agents, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are detailed.Oncologic agents produce a variety of CV adverse effects, including cardiomyopathy and heart failure, peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension (HTN), cardiac arrhythmias, valvular heart disease, and pulmonary HTN. Both the oncologist and the cardiologist need to be aware of such adverse effects and of the specific agents that produce them. They need to join forces to prevent, anticipate, recognize, and manage such complications.

Background: The mitochondrial Na+/Ca2+ exchanger (mNCX) has been implicated in the pathogenesis of arrhythmogenicity and myocardial reperfusion injury, rendering its inhibition a potential therapeutic strategy. We examined the effects of CGP-37157, a selective mNCX inhibitor, on arrhythmogenesis, infarct size (IS), and no reflow area (NRA) in a porcine model of ischemia-reperfusion. Methods: Forty pigs underwent myocardial ischemia for 60 minutes, followed by 2 hours of reperfusion. Animals were randomized to receive intracoronary infusion of 0.02 mg/kg CGP-37157 or vehicle, either before ischemia (n=17) or before reperfusion (n=17). Animals were monitored for arrhythmias. Myocardial area at risk (AR), IS, and NRA were measured by histopathology. Results: AR, NRA, and IS were comparable between groups. Administration of CGP-37157 before ischemia resulted in the following: (a) suppression of ventricular tachyarrhythmias (events/pig: 1.5±1.1 vs 3.5±1.9, p=0.014), (b) easier cardioversion of ventricular tachyarrhythmias (defibrillations required for cardioversion of each episode: 2.6±2.3 vs 6.2±2.1, p=0.006), and (c) decreased maximal depression of the J point (0.75±0.27 mm vs 1.75±0.82 mm, p=0.007), compared to controls. Administration of CGP-37157 before reperfusion expedited ST-segment resolution; complete ST-segment resolution within 30 minutes of reperfusion was observed in 7/8 CGP-37157-treated animals versus 1/9 controls (p=0.003). Conclusions: In a porcine model of myocardial infarction, intracoronary administration of CGP-37157 did not decrease IS or NRA. However, it suppressed ventricular arrhythmias, decreased depression of the J point during ischemia and expedited ST-segment resolution after reperfusion. These findings motivate further investigation of pharmacologic mNCX inhibition as a potential therapeutic strategy to suppress arrhythmias in the injured heart. Keywords: Ischemia-reperfusion injury, Myocardial infarction, Arrhythmias, Mitochondrial Na+/Ca2+ exchanger, CGP-37157

Psychiatric agents are among the most commonly prescribed medications. Despite the advent of newer generation agents, patients receiving them still experience cardiovascular (CV) side effects. However, these agents may have heterogeneous properties, calling for an individualized approach based on efficacy and also on the particular side effect profile of each specific agent. Proarrhythmic effects arising from drug-induced long-QT syndrome and consequent potentially life-threatening polymorphic ventricular arrhythmias in the form of torsade de pointes, the metabolic syndrome contributing to atherosclerosis and acute coronary syndromes, and drug-induced orthostatic hypotension raise major concerns. Of course, it is also crucial that fear of potential CV adverse effects does not deprive psychiatric patients of appropriate drug therapy. Modification of CV risk factors in psychiatric patients together with optimal management of their CV diseases and appropriate selection of psychotropic agents with greater efficacy and least CV toxicity are of paramount importance in mitigating CV risks and enhancing safety. Identifying patients at high risk of CV complications and close monitoring of all patients receiving these agents are crucial steps to prevent and manage such complications. All these issues are herein reviewed, relevant guidelines are discussed, and schemas are depicted that illustrate the interrelated connections among the psychotropic agents and their CV effects.

Objective Percutaneous closure of patent foramen ovale (PFO) and atrial septal defect (ASD) is routinely performed under general anesthesia or deep sedation and use of transesophageal (TEE) or intracardiac echocardiography, incurring longer duration and higher cost. We have used a simplified, economical, fluoroscopy-only guided approach with local anesthesia, and herein report our data. Methods The study includes 112 procedures in 110 patients with PFO (n = 75) or ASD (n = 35), with use of an Amplatzer occluder, heparin and prophylactic antibiotics. Balloon sizing guided ASD-device selection. All patients received aspirin and clopidogrel for 6 months, when they all underwent TEE. Results All PFOs but one (98.7%) and all (100%) ASDs were successfully closed with only one complication (local pseudoaneurysm). At the 6-month TEE, there was no residual shunt in PFO patients, but 2 ASD patients had residual shunts. During long-term (4.3-year) follow-up, no stroke recurrence in PFO patients, and no other problems were encountered. Among 54 patients suffering from migraine, symptom relief or resolution was reported by 45 (83.3%) patients. Conclusion Percutaneous placement of an Amplatzer occluder was safe and effective with use of local anesthesia and fluoroscopy alone. There were no recurrent strokes over >4 years. Migraine relief was reported by >80% of patients.

Background: Cardiac resynchronization therapy (CRT) device implantation is hampered by difficult placement of the left ventricular (LV) lead. We have routinely used a steerable electrophysiology catheter to guide coronary sinus (CS) cannulation and facilitate LV lead positioning. The aim of this prospective study is to present our results with this approach in 138 consecutive patients receiving a CRT device over 10 years. Methods: The study included 120 men and 18 women, aged 64.8±11.4 years, with coronary disease (n=63), cardiomyopathy (n=72), or other disease (n=3), and mean ejection fraction of 24.5±4.5%. Devices were implanted for refractory heart failure and dyssynchrony, all but 2 in the presence of left bundle branch block. Implanted devices included biventricular pacemakers (CRT-P) (n=33) and cardioverter defibrillators (CRT-D) (n=105). Results: Using the electrophysiology catheter, the CS could be engaged in 134 (97.1%) patients. In 4 patients failing CS cannulation, a dual-chamber device was implanted in 2, and bifocal right ventricular pacing was effected in 2. Bifocal (n=2) or conventional (n=1) systems were implanted in another 3 patients, in whom the LV lead got dislodged (n=2) or removed because of local dissection (n=1). Thus, finally, a CRT system was successfully established in 131 (94.9%) patients. There were 3 patients with CS dissection, of whom 1 was complicated by cardiac tamponade managed with pericardiocentesis. There were no perioperative deaths. During follow-up (31.0±21.2 months), clinical improvement was reported by 108 (82.4%) patients. Conclusion: Routine use of an electrophysiology catheter greatly facilitated CS cannulation and successful LV lead placement in ∼95% of patients undergoing CRT system implantation. Keywords: heart failure, cardiac resynchronization therapy, implantable cardioverter defibrillator, coronary sinus, left ventricular lead

A growing number of nonagenarians is recorded as life expectancy increases. Unfortunately, this extreme-aged group is plagued by increased prevalence of aortic stenosis amidst a higher occurrence of comorbidities that pose dilemmas to cardiologists and cardiac surgeons when having to choose a conservative or interventional treatment modality, and a surgical or transcatheter aortic valve implantation (TAVI) approach. TAVI is an expensive procedure, which also confers a higher mortality and morbidity risk in nonagenarians, compared to younger patients. Considering the physiologic rather the chronologic age alone, and adopting a shared-decision making approach (participatory medicine), it may be more realistic to determine a patient’s candidacy for this non-surgical therapeutic modality. Thus, it comes down to the patient selection process by having the heart team review each nonagenarian case individually and getting the patient and the family involved, always aiming to prolong and improve patient’s quality of life (QoL), but also taking into consideration patient preferences and values, sharing and respecting goals, realistic expectations, and end-of-life views and ideas. One should keep in mind that there is always the possibility that TAVI may be clinically futile for patients who have a multitude of comorbidities and extreme frailty, for whom a transition to palliative care might be prudent. Selecting nonagenarian patients with low comorbidity index and with no extreme frailty, adopting a minimalistic approach and paying attention to vascular access hemostasis may provide the elements that may lead to a successful, desirable and hopefully cost-effective outcome.

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO)

Over the recent years, the advent of single-shot techniques, such as circular catheter and cryoballoon ablation, has ushered in a new era in the catheter ablation approach and rhythm control strategies of patients with atrial fibrillation (AF). These techniques make it easier to navigate the heart and have the potential to decrease the threshold for, expand the access to, and increase patient and physician acceptance of rhythm-control therapies, that may lead to reduction of the AF disease burden and its socioeconomic impact. Due to technical issues the circular catheter technique is lagging behind, however the cryoballoon approach is progressing at a faster pace both in the field of technical advancements and clinical studies, all contributing to its rapid penetration in the electrophysiological community and rhythm management approaches toward the commonest cardiac arrhythmia. Comparative studies of the conventional point-by-point radiofrequency (RF) ablation technique and the cryoablation approach to pulmonary vein isolation (PVI), which constitutes the cornerstone of all ablation methods, seem to favor the cryoablation technique in certain aspects. The results of current studies converge in their conclusion that cryoablation employing current generation cryoballoons is a simplified and faster method compared to the conventional technique in achieving effective and durable PVI. Furthermore, investigators have recently proposed particular tips and parameters to serve as reliable predictors of successful and durable PVI that may enhance the clinical success of this single-shot ablation technique. These issues will be discussed in this overview and placed into perspective.

Background Cardiac implantable electronic device (CIED) implantation is complicated by infection still at a worrisome rate of 2-5%. Since early on during device implantation procedures, we have adopted an infection-preventive technique which has hitherto resulted in effective prevention of infections. Herein we present our results of applying this technique by a single operator in a prospective series of 762 consecutive patients undergoing device implantation. Methods A meticulous search for and treatment of active, occult, or smoldering infection was undertaken preoperatively. An aseptic/antiseptic technique was used for implantation of each device. Skin preparation is thorough with initial cleansing performed with alcohol followed by povidone-iodine 10% solution, which is also used in the wound and inside the pocket. In addition, we routinely use double gloving, and IV antibiotic prophylaxis 1 hour before and for 48 hours afterwards followed by oral antibiotic for 2-3 days after discharge. The skin is closed with absorbable sutures. The study includes 382 patients having a new pacemaker (n = 333) or battery change, system upgrade or lead revision (n = 49), and 380 patients having a new implantable cardioverter-defibrillator (ICD) (n = 296) or device replacement/upgrade/lead revision (n = 84). Results The pacemaker group, aged 70.2 ± 16.5 years, includes 18% VVI, 49% DDD, 29% VDD, and 4% cardiac resynchronization therapy (CRT) devices. The ICD group, aged 61.3 ± 13.0 years, with a mean ejection fraction of 36 ± 13%, includes 325 ICD and 55 CRT implants. Over 26.6 ± 33.4 months for the pacemaker group and 36.6 ± 38.3 months for the ICD group, infection occurred in one patient in each group (0.26%) having a device replacement. Conclusion A consistent and strict approach of aseptic/antiseptic technique with the use of double gloving and povidone-iodine solution within the pocket plus a 4-day regimen of antibiotic prophylaxis minimizes infections in CIED implants.

Medical management of atrial fibrillation (AF), the most common arrhythmia in the general population, has had modest efficacy in controlling symptoms and restoring and maintaining sinus rhythm. Since the seminal observation in 1998 that pulmonary veins host the triggers of AF in the majority of cases, electrical isolation of all pulmonary veins constitutes the cornerstone of ablation in patients with symptomatic AF. However, due to the elaborate and tedious technique of the conventional point-by-point method with radiofrequency ablation guided by electroanatomical mapping, newer, more versatile single-shot techniques, such as cryoballoon ablation, have been sought and developed over recent years and are progressively prevailing. Cryoballoon ablation appears to be the most promising practical and effective approach, and we review it here by presenting all available relevant data from the literature as well as from our own experience in an attempt to apprise colleagues of the significant progress made over the last several years in this important field of electrophysiology.

Heart failure (HF) with preserved ejection fraction (HFpEF) represents half of HF patients, who are more likely older, women, and hypertensive. Mortality rates in HFpEF are higher compared with age- and comorbidity-matched non-HF controls and lower than in HF with reduced ejection fraction (HFrEF); the majority (50–70%) are cardiovascular (CV) deaths. Among CV deaths, sudden death (SD) (~ 35%) and HF-death (~ 20%) are the leading cardiac modes of death; however, proportionally, CV deaths, SD, and HF-deaths are lower in HFpEF, while non-CV deaths constitute a higher proportion of deaths in HFpEF (30–40%) than in HFrEF (~ 15%). Importantly, the underlying mechanism of SD has not been clearly elucidated and non-arrhythmic SD may be more prominent in HFpEF than in HFrEF. Furthermore, there is no specific strategy for identifying high-risk patients, probably due to wide heterogeneity in presentation and pathophysiology of HFpEF and a plethora of comorbidities in this population. Thus, the management of HFpEF remains problematic due to paucity of data on the clinical benefits of current therapies, which focus on symptom relief and reduction of HF-hospitalization by controlling fluid retention and managing risk-factors and comorbidities. Matching a specific pathophysiology or mode of death with available and novel therapies may improve outcomes in HFpEF. However, this still remains an elusive target, as we need more information on determinants of SD. Implantable cardioverter-defibrillators (ICDs) have changed the landscape of SD prevention in HFrEF; if ICDs are to be applied to HFpEF, there must be a coordinated effort to identify and select high-risk patients.

Cardiac amyloidosis or amyloid cardiomyopathy (ACM), commonly resulting from extracellular deposition of amyloid fibrils consisted of misfolded immunoglobulin light chain (AL) or transthyretin (TTR) protein, is an underestimated cause of heart failure and cardiac arrhythmias. Among the three types of cardiac amyloidosis (wild-type or familial TTR and light-chain), the wild-type (Wt) TTR-related amyloidosis (ATTR) is an increasingly recognized cause of heart failure with preserved ejection fraction (HFpEF), and amyloidosis should be considered in the differential diagnosis of this heart failure group of patients. Recent advances in the diagnosis and drug treatment of ACM have ushered in a new era in early disease detection and better management of these patients. Certain clues in cardiac and extracardiac manifestations of ACM may heighten clinical suspicion and guide further confirmatory testing. Newer noninvasive imaging methods (strain echocardiography, cardiac magnetic resonance and bone scintigraphy) may obviate the need for endomyocardial biopsy in ATTR patients, while newer targeted therapies may alter the adverse prognosis in these patients. Early recognition of ACM is crucial in halting the disease process before irreversible organ damage occurs. Chemotherapy and stem-cell transplantation combined with immunomodulatory therapy may also favorably affect the course and prognosis of light chain ACM. Finally, in select patients with end-stage disease, heart transplantation may render results comparable to non-ACM patients. All these issues are herein reviewed.

To review comparative efficacy and tolerability data between the two main mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, in patients with resistant hypertension (HTN). The focus was whether spironolactone, being the classical non-selective agent that has been used for years, albeit with several anti-androgenic side effects, can be rivaled by eplerenone, an apparently weaker, but better tolerated, more selective MRA. Evidence has accumulated that resistant HTN is generally volume-dependent, attributable to varying degrees of aldosterone excess with its attendant renal effects of sodium and fluid retention. Such aldosteronism may be due to an underestimated occurrence of primary aldosteronism; however, it more commonly occurs separately from it and independent from angiotensin II. The aldosterone-induced volume excess placed at the root of the development of resistant HTN in a large number of patients, together with the extrarenal deleterious effects of aldosterone, such as endothelial dysfunction, vascular remodeling and increased arterial stiffness, cardiac hypertrophy, and fibrosis can all be counterbalanced by the administration of MRAs. In the absence of a direct comparison between spironolactone and eplerenone, and in light of compelling evidence provided by the recently reported results of the PATHWAY-2 and ReHOT studies, spironolactone has been established as the most effective add-on anti-aldosterone therapy in resistant HTN. The data on use of eplerenone continue to emerge and are quite encouraging. Despite the lack of direct comparative data, the weight of evidence regarding efficacy is currently in favor of spironolactone. However, the data on the efficacy of eplerenone are promising but still being accumulated suggesting this agent as an alternative to spironolactone and certainly as the preferred choice for those not tolerating spironolactone, especially for patients developing anti-androgenic side effects like breast tenderness, gynecomastia/mastodynia, and/or sexual dysfunction. Both these agents appear to have several other pleiotropic effects that confer cardioprotection and renoprotection beyond their antihypertensive effect. Potassium levels and renal function need to be closely monitored during administration of these therapies. Future comparative studies may shed more light on these issues, while emerging newer agents may offer better and safer therapeutic options.