Current Cardiology Reviews - Volume 13, Issue 4, 2017

Purpose: This review provides an overview and quality assessment of existing interventions, assessing the intervention types that are most effective at increasing enrolment and adherence to cardiac rehabilitation in older patients aged ≥65 years Methods: The review of the literature was performed using electronic databases to search for randomised controlled trials that aimed to increase enrolment and/or adherence to cardiac rehabilitation in older patients aged ≥65 years. The main key words were cardiac rehabilitation, enrolment, adherence and older patients. Studies were included if; (1) the intervention targeted improving enrolment and/or adherence to at least one of the following components of the cardiac rehabilitation programme: exercise, education or maintaining lifestyle changes; (2) assess the effectiveness of an intervention on increasing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (3) include measures for assessing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (4) the study included patients with a mean age of ≥65 years who were deemed eligible to participate in a cardiac rehabilitation programme. Included studies could be published in any language and there were no date restrictions for included studies. Studies focusing on pharmaceutical adherence were not included for the purpose of this review. Results: Seven studies were included, with four investigating enrolment (1944 participants) and three assessing adherence to intervention programmes (410 participants). Three studies (1919 participants) reported higher enrolment to cardiac rehabilitation in the intervention group. Two studies that reported increases in enrolment to cardiac rehabilitation were deemed to have an unclear or high risk of bias. All three studies (410 participants) reported better adherence to cardiac rehabilitation in the intervention group when compared to the control group. Two studies that reported better completion of cardiac rehabilitation were deemed to have an unclear or high risk of bias. No formal meta-analysis was conducted due to the observed multiple heterogeneity among outcome measures, the low number of included studies and variability in study designs. Conclusion: This review found only weak evidence to suggest that interventions can increase enrolment or adherence to cardiac rehabilitation programmes for patients aged ≥65 years, therefore no practice recommendations could be made and further high-quality research is needed in this population group.

Background: Interatrial block (IAB) is due to disruption in the Bachmann region (BR). According to whether interatrial electrical conduction is delayed or completely blocked through the BR, it can be classified as IAB of first, second or third degree. On the surface electrocardiogram, a P wave ≥ 120 ms (partial IAB) is observed or associated to the prolongation of the P wave with a biphasic (positive / negative) morphology in the inferior leads (advanced IAB). Bayes syndrome is defined as an advanced IAB associated with atrial arrhythmia, more specifically atrial fibrillation. Objective and Conclusion: The purpose of this review is to describe the latest evidence about an entity considered an anatomical and electrical substrate with its own name, which may be a predictor of supraventricular arrhythmia and cardioembolic cerebrovascular accidents, as well as the role of new imaging techniques, such as echocardiographic strain and cardiac magnetic resonance imaging, in characterizing atrial alterations associated with this syndrome and generally in the study of anatomy and atrial function.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been gaining major attention recently after the emergence of data showing the promising role of these proteins in lipid homeostasis and atherosclerosis process, glucose and blood pressure regulation. Materials and Methods: PubMed, EMBASE, Scholar and Scopus databases were searched to identify randomized controlled trials, observational studies, in-vitro trials and reviews about the role of PCSK9 in cardiovascular homeostasis. Results: PCSK9 was found to have major impact on lipid homeostasis and inflammatory process through regulation of low-density lipoprotein receptors. Furthermore, inflammation was found to stimulate the expression of PCSK9 in various cells. As for glomerular proteinuria, a positive correlation was determined between PCSK9 levels and the degree of proteinuria. Hypertension, a major cardiovascular risk factor, is likely affected by PCSK9 levels through their role on epithelial sodium channel (ENaC) surface expression. Likewise, some studies show that PCSK9 is associated with higher fasting blood glucose and plasma insulin, demonstrating a potential role of PCSK9 in glucose homeostasis. The role of PCSK9 in cardiovascular homeostasis is one that is still not completely unraveled. Conclusion: Studies have clearly shown the implication of PCSK9 in the cardiovascular risk factors: the higher the PCSK9 levels, the higher the risk of atherosclerosis, fasting plasma glucose and insulin resistance. Inhibiting PCSK9 may therefore theoretically prove to present great benefits in diabetic patients with high cardiovascular risk.

Background: Pre-existing chronic kidney disease (CKD) portends adverse outcomes following heart valve surgery. However, only limited and conflicting evidence is available on the impact of CKD on outcomes following transcatheter aortic valve replacement (TAVR). The objective of this review was to evaluate the effect of pre-existing CKD on TAVR outcomes. Methods: We performed a systematic electronic search using the PRISMA statement to identify all randomized controlled trials and observational studies investigating the effect of pre-existing CKD on outcomes following TAVR. 30-day and long-term outcomes were measured comparing patients with Glomerular filtration rate (GFR) ≥60 to those with GFR <60. Results: Ten studies were analyzed comprising of 8688 patients. Compared to patients with GFR ≥60, those with GFR < 60 had worse 30-day all cause mortality (OR 1.40, 95% CI: 1.13-1.73), cardiovascular mortality (OR 1.66, 95% CI: 1.04-2.67), strokes (OR 1.39, 95% CI: 1.05-1.85), acute kidney injury (OR 1.42, 95% CI: 1.21-1.66) and the risk for dialysis (OR 2.13, 95% CI: 1.07-4.22). There was no difference in device success (p=0.873), major or life threatening bleeds (p = 0.302), major vascular complications (p=0.525), need for pacemaker implantation (p = 0.393) or paravalvular leaks (p = 0.630). All-cause mortality at 1 year was also significantly higher in patients with GFR <60 (OR 1.80, 95% CI: 1.26-2.56). Conclusion: Pre-existing CKD defined as GFR <60 is a strong predictor of worse short and longterm outcomes following TAVR. Active measures should be taken to mitigate the postprocedure risk in these group of patients.

Background: Hemodynamics during dynamic exercise is finely regulated by some neural mechanisms. One of these mechanisms is the metabolic part of the exercise pressor reflex, i.e. the muscle metaboreflex. Hemodynamic response during the metaboreflex is characterised by the recruitment of the reserves in cardiac inotropism, pre-load, after-load and chronotropism. If one of these reserves is exhausted, then the cardiovascular response is achieved by recruiting one of the other reserves, thereby indicating a remarkable plasticity of the control of circulation. Conclusion: In this review, the effects of a number of cardiovascular diseases - such as heart failure, heart failure with preserved ejection fraction, hypertension, type 1 and type 2 diabetes mellitus, obesity and metabolic syndrome - on hemodynamics during the metaboreflex are reviewed.

Opinion Statements: Cardiovascular diseases (CVDs) encompass a range of conditions extending from congenital heart disease to acute coronary syndrome most of which are heterogenous in nature and some of them are multiple genetic loci. However, the pathogenesis of most CVDs remains incompletely understood. The advance in genome-editing technologies, an engineering process of DNA sequences at precise genomic locations, has enabled a new paradigm that human genome can be precisely modified to achieve a therapeutic effect. Genome-editing includes the correction of genetic variants that cause disease, the addition of therapeutic genes to specific sites in the genomic locations, and the removal of deleterious genes or genome sequences. Site-specific genome engineering can be used as nucleases (known as molecular scissors) including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems to provide remarkable opportunities for developing novel therapies in cardiovascular clinical care. Here we discuss genetic polymorphisms and mechanistic insights in CVDs with an emphasis on the impact of genome-editing technologies. The current challenges and future prospects for genomeediting technologies in cardiovascular medicine are also discussed.

Background: Transseptal puncture (TSP) remains a demanding procedural step in accessing the left atrium with inherent risks and safety concerns, mostly related to cardiac tamponade. Objective: Based on our own experience with 249 TSP procedures and in-depth literature review, we present our results and offer several tips and tricks that may render TSP successful and safe. Methods: This prospective study comprised 249 consecutive patients (146 men), aged 41.6±17.4 years, undergoing TSP by a single operator for ablation of a variety of arrhythmias, mostly related to left accessory pathways (n=145) or left atrial tachycardias (n=33) and more recently, atrial fibrillation (n=70). TSP was guided by fluoroscopy alone in all patients without the use of echocardiography imaging. In addition, an extensive literature review of TSP-related topics was carried out in PubMed, Scopus and Google Scholar. Results: Among 249 patients, 33 patients were children or young adolescents (aged 7-18 years); 14 patients were undergoing a repeat procedure. Patients with a manifest accessory pathway were the youngest (mean age 33.7±15.9) and patients with atrial fibrillation the oldest (mean age 56.0±10.8 years). A successful TSP was accomplished in 247 patients (99.2%). Two (0.8%) procedures were complicated by cardiac tamponade managed successfully with pericardiocentesis or surgical drainage. Review of the literature revealed no systematic reviews and meta-analyses of TSP studies; however, several patient series have documented that fluoroscopy-guided TSP, with various modifications in the technique employed in the present series, have been effective in 95-100% of the cases with a complication rate ranging from 0.0% to 6.7%, albeit with a mortality rate of 0.018%- 0.2%. Echo imaging techniques were employed in cases with difficult TSP. Conclusion: Employing a standardized protocol with use of fluoroscopy alone minimized serious complications to 0.8% (2 patients) among 249 consecutive patients undergoing TSP for ablation of a variety of cardiac arrhythmias. Based on this single-operator experience and review of the literature, a list of practical tips and tricks is provided for a successful and safe procedure, reserving the more expensive and patient inconveniencing echo-imaging techniques for difficult or failed cases.

Background: Evolocumab is a potent lipid-lowering drug that decreases plasma levels of lowdensity lipoprotein cholesterol (LDL-C) by 50-60%. FOURIER is a landmark randomized trial involving 27,564 patients with established cardiovascular disease already on statins and plasma LDLC levels > 70 mg/dl. Objective: The main objective of FOURIER was to examine the effects of evolocumab on cardiovascular events. Results: After a mean follow-up of 2.2 years, evolocumab significantly decreased the primary endpoint (composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) by 15% compared to placebo [hazard ratio 0.85 (95% CI, 0.79-0.92)], but no significant effect was found on mortality. The most common adverse effect of evolocumab was mild injection site reaction occurring in 2.1% of patients versus 1.6% of patients receiving placebo. Conclusion: These results support the use of evolocumab as add-on therapy to statins for high cardiac- risk patients not achieving optimal goals of LDL-C. Longer-term studies are needed to further clarify the efficacy and safety of evolocumab.

Background: Patients with acute coronary syndromes (ACS) and a history of atrial fibrillation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. We examined studies comparing clinical outcomes on DAPT versus TT for patients with AF and ACS. Methods: We searched Medline, Medline pending, EMBASE and Evidence-Based Medicine Reviews databases for studies published between January 2000 to December 2016 in AF patients with ACS that compared DAPT and TT that reported ischaemic and/or bleeding outcomes. Studies that were not purely an AF population were excluded. Results: Ten studies were included in the review, all of which were observational, 8 of which were retrospective. None of the studies detailed the specifics of treatment allocation. All but one were of AF patients with a mix of stable coronary disease and ACS patients. TT was associated with increased bleeding when compared to DAPT, with adjusted odds ratios ranging from 1.25 to 6.84. While the largest study reported a reduction in stroke associated with TT (odds ratio 0.67), two other studies reported non-significant increases in stroke with TT. Variable composite ischaemic endpoints were reported, none showing a statistical significant difference between DAPT and TT. Conclusion: In patients with ACS and AF, TT is likely to be associated with increased risk of bleeding, without a clear reduction in ischaemic endpoints. The quality of the evidence to support current guidelines for this patient group was generally poor.