Treatment of Functional Mitral Regurgitation in Heart Failure Abstract Purpose of Review To analyze the current state of the art of functional mitral regurgitation (FMR) treatment. Recent Findings The first-line treatment of severe FMR consists of guideline medical therapy (GMT) and resynchronization therapy when indicated; the impact of new medical therapies like sacubitril/valsartan needs further assessment. Valvular intervention may be considered in FMR symptomatic patients despite GMT, and can be performed surgically or percutaneously. MitraClip is a safe percutaneous procedure associated with symptoms improvement. Recently, the COAPT trial showed superior outcomes for MitraClip versus GMT contrasting the MITRA-FR trial which showed no benefit of MitraClip compared with GMT. These results should be interpreted as complementary rather than opposite. Summary The COAPT trial provided a “proof of concept” that percutaneous treatment of severe FMR in patients without too advanced left ventricular disease translates into a prognostic benefit. Careful patient selection will play a critical role in defining the clinical niche for successful interventions.

How To Assess a Claudication and When To Intervene Abstract Purpose of the Review Peripheral artery disease (PAD) affects close to 200 million people worldwide. Claudication is the most common presenting symptom for patients with PAD. This review summarizes the current diagnostic and treatment options for patients with claudication. Comprehensive history and physical examination in order to differentiate between claudication secondary to vascular disease vs. neurogenic causes is paramount for initial diagnosis. Ankle-brachial index is the most commonly used test for screening and diagnostic purposes. Treatment consists of four different approaches, which are best utilized in combination: non-pharmacological treatment for claudication improvement, pharmacological treatment for claudication improvement, pharmacological treatment for secondary risk reduction, and interventional treatment for claudication improvement. Recent Findings Cilostazol is the only Food and Drug Administration (FDA)-approved agent for symptomatic treatment of claudication. Supervised exercise programs provide the maximum benefit for claudication improvement, but home-based exercise programs are an alternative. High-intensity statins and an antiplatelet agent should be prescribed to all patients with PAD. Angiotensin-converting-enzyme inhibitors can provide additional risk reduction, especially in patients with diabetes or hypertension. Rivaroxaban of low dosage (2.5 mg twice daily) in combination with aspirin further decreases cardiovascular risk, but this reduction comes at the cost of higher bleeding risk. Summary Peripheral artery disease (PAD) is a form of atherosclerotic disease that affects hundreds of millions of people worldwide—one of its most common manifestations is intermittent claudication (IC), which results from insufficient blood flow to meet the metabolic demands of an affected extremity. This paper reviews the current literature regarding the workup, diagnosis, diagnostic modalities, treatment options, and management of intermittent claudication.

Cardiovascular Consequences of Obstructive Sleep Apnea Abstract Purpose of Review To review the clinical evidence for a relationship between obstructive sleep apnea and hypertension, arrhythmias, coronary artery disease, and congestive heart failure. Recent Findings Current data show that obstructive sleep apnea is a risk for cardiovascular disease. Studies have linked untreated moderate to severe obstructive sleep apnea to hypertension, cardiac arrhythmias, coronary artery disease, and congestive heart failure. However, uncertainty regarding benefits of treatment of obstructive sleep apnea to reduce the risk of cardiovascular disease still exists. The issue of poor compliance has been an on-going limitation of CPAP trials. Summary Evidence shows obstructive sleep apnea is a risk factor for cardiovascular disease but trials have yet to clarify if cardiovascular disease morbidity and mortality decreases with treatment of the apnea. Future treatment trials are needed to address the question of whether treatment decreases cardiovascular risk in patients with obstructive sleep apnea.

On the Road to Regeneration: “Tools” and “Routes” Towards Efficient Cardiac Cell Therapy for Ischemic Cardiomyopathy Abstract Purpose of Review Cardiac regenerative medicine is a field bridging together biotechnology and surgical science. In this review, we present the explored surgical roads to cell delivery and the known effects of each delivery method on cell therapy efficiency. We also list the more recent clinical trials, exploring the safety and efficacy of delivery routes used for cardiac cell therapy approaches. Recent Findings There is no consensus in defining which way is the most suitable for the delivery of the different therapeutic cell types to the damaged heart tissue. In addition, it emerged that the “delivery issue” has not been systematically addressed in each clinical trial and for each and every cell type capable of cardiac repair. Summary Cardiac damage occurring after an ischemic insult triggers a cascade of cellular events, eventually leading to heart failure through fibrosis and maladaptive remodelling. None of the pharmacological or medical interventions approved so far can rescue or reverse this phenomenon, and cardiovascular diseases are still the leading cause of death in the western world. Therefore, for nearly 20 years, regenerative medicine approaches have focused on cell therapy as a promising road to pursue, with numerous preclinical and clinical testing of cell-based therapies being studied and developed. Nonetheless, consistent clinical results are still missing to reach consensus on the most effective strategy for ischemic cardiomyopathy, based on patient selection, diagnosis and stage of the disease, therapeutic cell type, and delivery route.

Transcaval Access for Large Bore Devices Abstract Purpose of Review Examine the latest data and techniques regarding transcaval access and closure. Recent Findings Transcaval access was proven to be a feasible and a translatable skill in a 100 patient open-label prospective study. No late complications from fistulas occurred and of all patients alive at 1 year, one fistula remained open. Summary Transcaval is a viable access route for large bore devices. With adequate planning, bleeding and vascular complications are minimal. It should be integrated into the rubric of transcatheter large bore access.

Mitral Valve Disease in Hypertrophic Cardiomyopathy:Evaluation and Management Abstract Purpose of Review To discuss the critical role of the mitral valve (MV) in the pathophysiology of obstruction in hypertrophic cardiomyopathy (HCM), evaluation of the MV in HCM, the impact of MV characteristics on treatment in HCM, and management of the MV at the time of septal myectomy. Recent Findings Multimodality imaging helps describe mitral abnormalities in HCM, though significant controversy persists on what to do with these abnormalities. In certain cases, intervention on the MV may be necessary, although outcomes may be worse in those who undergo mitral interventions. Summary Thorough assessment of MV anatomy and function is paramount in evaluating a patient with HCM. Emphasis should be placed on thorough evaluation and description of mitral abnormalities in HCM. Given significant practice variation, future studies could compare MV practice differences across institutions and how these impact long-term outcomes.

Sense of Purpose in Life and Cardiovascular Disease: Underlying Mechanisms and Future Directions Abstract Purpose of Review In this review, we synthesize recent research that has reported associations of a higher sense of purpose in life with reduced risk of developing cardiovascular disease (CVD), and then explore mechanisms that might underlie these associations. Recent Findings Accumulating observational and experimental evidence suggests that having a higher sense of purpose might influence CVD risk through three pathways: (1) enhancement of other psychological and social resources that buffer against the cardiotoxic effects of overwhelming stress; (2) indirect effects through health behaviors; and (3) direct effects on biological pathways. Summary A sense of purpose in life is emerging as an independent risk factor for incident CVD. A key remaining question is whether purpose causally effects CVD risk; in the “Future Research Directions” section, we focus on work needed to establish causality and provide suggestions for next steps.

Optimal Dietary Strategies for Prevention of Atherosclerotic Cardiovascular Disease in Diabetes: Evidence and Recommendations Abstract Purpose of Review This review presents the current available evidence of the effects of several dietary patterns on atherosclerotic cardiovascular disease (ASCVD) risk in patients with type 2 diabetes (T2D). Recent Findings Evidence demonstrates improvements in cardiovascular risk factors with some dietary patterns in the general population. However, evidence is limited for glycemic control and cardiovascular benefit in patients with T2D for Dietary Approaches to Stop Hypertension and plant-based dietary patterns. Evidence suggests that carbohydrate-restricted dietary patterns improve glycemic control and decrease the use of anti-hyperglycemic medications. The Mediterranean dietary pattern has the most evidence for glycemic control and decreased ASCVD risk in patients with T2D. There is no evidence on ASCVD outcomes in patients with T2D for any other dietary pattern. Summary The Mediterranean dietary pattern has the most evidence for cardiovascular benefit in patients with T2D. Future research should examine the effect of dietary patterns on ASCVD outcomes.

Cell Cycle–Mediated Cardiac Regeneration in the Mouse Heart Abstract Purpose of Review Many forms of heart disease result in the essentially irreversible loss of cardiomyocytes. The ability to promote cardiomyocyte renewal may be a promising approach to reverse injury in diseased hearts. The purpose of this review is to describe the impact of cardiomyocyte cell cycle activation on cardiac function and structure in several different models of myocardial disease. Recent Findings Transgenic mice expressing cyclin D2 (D2 mice) exhibit sustained cardiomyocyte renewal in the adult heart. Earlier studies demonstrated that D2 mice exhibited progressive myocardial regeneration in experimental models of myocardial infarction, and that cardiac function was normalized to values seen in sham-operated litter mates by 180 days post-injury. D2 mice also exhibited markedly improved atrial structure in a genetic model of atrial fibrosis. More recent studies revealed that D2 mice were remarkably resistant to heart failure induced by chronic elevated afterload as compared with their wild type (WT siblings), with a 6-fold increase in median survival as well as retention of relatively normal cardiac function. Finally, D2 mice exhibited a progressive recovery in cardiac function to normal levels and a concomitant reduction in adverse myocardial remodeling in an anthracycline cardiotoxicity model. Summary The studies reviewed here make a strong case for the potential utility of inducing cardiomyocyte renewal as a means to treat injured hearts. Several challenges which must be met to develop a viable therapeutic intervention based on these observations are discussed.

Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors Abstract Purpose of Review To review the clinical trial data and underlying mechanistic principles in support of the robust cardiovascular (CV) benefits, in particular, heart failure (HF) outcomes association with sodium-glucose co-transporter-2 (SGLT2) inhibitors. Recent Findings Several large CV outcome trials in patients with type 2 diabetes mellitus (T2DM) and with either established atherosclerotic CV disease (ASCVD) or at high risk for ASCVD reveal that SGLT2 inhibitors cause reductions in CV and HF endpoints. The reduction in ASCVD appears to be confined to those with established ASCVD on the order of ≈ 14%, as does the mortality benefit—all-cause and CV-related. However, hospitalization for HF are reduced by ≈ 33% and occur regardless of baseline patient characteristics. The unprecedented HF outcomes are theorized to occur via several possible mechanisms and include optimization of conventional ASCVD risk factors, improvement in hemodynamics, prevention of cardiac and renal remodeling, inhibition of hormone dysregulation, use of more efficient metabolic substrates, ion channel inhibition, anti-inflammatory effects, and anti-oxidant effects. Summary Recent evidence has unveiled the irrefutable data that SGLT2 inhibitors reduce CV events in patients with T2DM, with a profound effect on reductions in hospitalization for HF. Though several mechanisms conveying this benefit are suggested, most are based in limited data requiring further validation. Nonetheless, the arrival of SGLT2 inhibitors has ushered in a new era of CV risk reductions therapies.