Epicardial Adipose Tissue Thickness and Preserved Ejection Fraction Heart Failure.

PURPOSE OF THE REVIEW: Preserved ejection fraction heart failure and obesity frequently coexist. Whether obesity plays a consistent role in the pathogenesis of preserved ejection fraction heart failure is unclear. Accumulation of visceral adiposity underlies the pathogenic aftermaths of obesity. However, visceral adiposity imaging is assessed by computed tomography or magnetic resonance and thus not routinely available. In contrast, epicardial adiposity thickness is assessed by echocardiography and thus routinely available. We review the rationale for assessing epicardial adiposity thickness in patients with preserved ejection fraction heart failure and elevated body mass index. RECENT FINDINGS: Body mass index correlates poorly with visceral, and epicardial adiposity. Visceral and epicardial adiposity enlarges as preserved ejection fraction heart failure progresses. Epicardial adiposity may hasten the progression of coronary artery disease and impairs left ventricular sub-endocardial perfusion and diastolic function. Epicardial adiposity thickness may help monitor the therapeutic response in patients with preserved ejection failure heart failure and elevated body mass index.

Extent of Low-density Lipoprotein Cholesterol Reduction and All-cause and Cardiovascular Mortality Benefit: A Systematic Review and Meta-analysis.

ABSTRACT: Lipid-modifying agents steadily lower low-density lipoprotein cholesterol (LDL-C) levels with the aim of reducing mortality. A systematic review and meta-analysis were conducted to determine whether all-cause or cardiovascular (CV) mortality effect size for lipid-lowering therapy varied according to the magnitude of LDL-C reduction. Electronic databases were searched, including PubMed and ClinicalTrials.gov , from inception to December 31, 2019. Eligible studies included randomized controlled trials that compared lipid-modifying agents (statins, ezetimibe, and PCSK-9 inhibitors) versus placebo, standard or usual care or intensive versus less-intensive LDL-C-lowering therapy in adults, with or without known history of CV disease with a follow-up of at least 52 weeks. All-cause and CV mortality as primary end points, myocardial infarction, stroke, and non-CV death as secondary end points. Absolute risk differences [ARD (ARDs) expressed as incident events per 1000 person-years], number needed to treat (NNT), and rate ratios (RR) were assessed. Sixty randomized controlled trials totaling 323,950 participants were included. Compared with placebo, usual care or less-intensive therapy, active or more potent lipid-lowering therapy reduced the risk of all-cause death [ARD -1.33 (-1.89 to -0.76); NNT 754 (529-1309); RR 0.92 (0.89-0.96)]. Intensive LDL-C percent lowering was not associated with further reductions in all-cause mortality [ARD -0.27 (-1.24 to 0.71); RR 1.00 (0.94-1.06)]. Intensive LDL-C percent lowering did not further reduce CV mortality [ARD -0.28 (-0.83 to 0.38); RR 1.02 (0.94-1.09)]. Our findings indicate that risk reduction varies across subgroups and that overall NNTs are high. Identifying patient subgroups who benefit the most from LDL-C levels reduction is clinically relevant and necessary.

Integrated Care Model of Adiposity-Related Chronic Diseases.

PURPOSE OF REVIEW: Although obesity is a disease, most patients with obesity do not undergo effective treatment nor adhere to long-term care. We examine the barriers that patients with obesity confront when searching for effective treatment and propose an integrated care model of adiposity-related chronic diseases in a cardio-renal metabolic unit. RECENT FINDINGS: The current care of obesity is fragmented between primary care providers, medical specialists and metabolic bariatric surgeons with little or no coordination of care between these providers. The current care of obesity heavily focuses on weight loss as the primary aim of treatment thereby reenforcing the weight stigma and turning patients away from effective therapy like metabolic bariatric surgery. An interdisciplinary cardio-renal metabolic unit that, besides weight loss, emphasizes prevention/remission of adiposity-related chronic diseases may deliver thorough and rewarding care to most patients with obesity.

Cardiovascular Disease Risk Reduction and Body Mass Index.

PURPOSE OF REVIEW: Anti-hypertensive and lipid lowering therapy addresses only half of the cardiovascular disease risk in patients with body mass index > 30 kg/m2, i.e., obesity. We examine newer aspects of obesity pathobiology that underlie the partial effectiveness of anti-hypertensive lipid lowering therapy for the reduction of cardiovascular disease risk in obesity. RECENT FINDINGS: Obesity-related insulin resistance, vascular endothelium dysfunction, increased sympathetic nervous system/renin-angiotensin-aldosterone system activity, and glomerulopathy lead to type 2 diabetes, coronary atherosclerosis, and chronic disease kidney disease that besides hypertension and dyslipidemia increase cardiovascular disease risk. Obesity increases cardiovascular disease risk through multiple pathways. Optimal reduction of cardiovascular disease risk in patients with obesity is likely to require therapy targeted at both obesity and obesity-associated conditions.

Consideration Regarding the Analysis of Randomized Controlled Trials in the Era of Evidence-based Medicine.

ABSTRACT: Analysis of randomized controlled trials (RCTs) is the cornerstone of evidence-based medicine, therapeutic guidelines and ultimately daily practice. However, 2 issues contribute to cloud the analysis of RCTs. Industry-sponsored RCTs aim at capturing as large indications as possible and clinicians rely excessively on P value statistical significance for the evaluation of the findings. To be most valuable to practitioners, analysis of RCTs needs to provide absolute risk reduction, number of patients needed to treat, fragility index along with the estimation of lost to follow-up patients, and outcome postponement (gain in survival time). We analyzed few major cardiovascular RCTs and assessed the robustness of their findings. Our suggested analytic parameters may be further used in future systematic reviews and meta-analyses.

Obesity, Hypertension, and Bariatric Surgery.

PURPOSE OF REVIEW: Obesity increases the risk of hypertension. However, blood pressure decreases before any significant loss of body weight after bariatric surgery. We review the mechanisms of the temporal dissociation between blood pressure and body weight after bariatric surgery. RECENT FINDINGS: Restrictive and bypass bariatric surgery lower blood pressure and plasma leptin levels within days of the procedure in both hypertensive and normotensive morbidly obese patients. Rapidly decreasing plasma leptin levels and minimal loss of body weight point to reduced sympathetic nervous system activity as the underlying mechanism of rapid blood pressure decline after bariatric surgery. After the early rapid decline, blood pressure does not decrease further in patients who, while still obese, experience a steady loss of body weight for the subsequent 12 months. The divergent effects of bariatric surgery on blood pressure and body weight query the role of excess body weight in the pathobiology of the obesity phenotype of hypertension. The decrease in blood pressure after bariatric surgery is moderate and independent of body weight. The lack of temporal relationship between blood pressure reduction and loss of body weight for 12 months after sleeve gastrectomy questions the nature of the mechanisms underlying obesity-associated hypertension.

Weight Reduction for Obesity-Induced Heart Failure with Preserved Ejection Fraction.

PURPOSE OF REVIEW: Heart failure with preserved ejection fraction mainly affects the elderly. The obesity phenotype of heart failure with preserved ejection fraction reflects the coexistence of two highly prevalent conditions in the elderly. Obesity may also lead to heart failure with preserved ejection fraction in middle-aged persons, especially in African American women. RECENT FINDINGS: Obesity is twice as common in middle-aged than in elderly persons with heart failure with preserved ejection fraction. Obese middle-aged persons with heart failure with preserved ejection fraction are less likely to be Caucasian and to have atrial fibrillation or chronic kidney disease as comorbidities than elderly patients with heart failure with preserved ejection fraction. Obesity-associated low-grade systemic inflammation may induce/heighten inflammatory activation of the coronary microvascular endothelium, leading to cardiomyocyte hypertrophy/ stiffness, myocardial fibrosis, and left ventricular diastolic dysfunction. Both substantial weight reduction with bariatric surgery and lesser levels of weight reduction with caloric restriction are promising therapeutic approaches to obesity-induced heart failure with preserved ejection fraction.

Epicardial Adipose Tissue and Cardiovascular Disease.

PURPOSE OF REVIEW: Epicardial adipose tissue has been associated with the development/progression of cardiovascular disease. We appraise the strength of the association between epicardial adipose tissue and development/progression of cardiovascular diseases like coronary artery disease, atrial fibrillation, and heart failure with preserved ejection fraction. RECENT FINDINGS: Cross-sectional clinical and translational correlative studies have established an association between epicardial adipose tissue and progression of coronary artery disease. Recent studies question this association and underline the need for longitudinal studies. Epicardial adipose tissue also plays a definite role in the pathobiology of atrial fibrillation and its recurrence after ablation. In contrast to an early paradigm, epicardial adipose tissue does not appear to play a key role in the pathogenesis of heart failure with preserved ejection fraction in obese patients. The association of epicardial adipose tissue with atrial fibrillation is robust. In contrast, the association of epicardial adipose tissue with coronary artery disease and heart failure with preserved ejection fraction is tenuous. Additional research, including longitudinal studies, is needed to confirm or refute these proposed associations.

Obesity and Pulmonary Hypertension.

PURPOSE OF REVIEW: Whether the present obesity epidemic will increase the prevalence of pulmonary hypertension over the next decades is unclear. We review the obesity-related mechanisms that may further the development and progression of pulmonary hypertension. RECENT FINDINGS: Systemic and local inflammation, insulin resistance and oxidative stress contribute to the pathobiology of obesity and pulmonary arterial hypertension. Preliminary data suggest that expansion of adipose tissue surrounding the pulmonary artery may hasten the progression of pulmonary arterial hypertension in obese persons. Further, obesity-associated cardiac and pulmonary conditions may increase the prevalence of groups 2 and 3 pulmonary hypertension. The obesity epidemic is likely to increase the prevalence of pulmonary arterial hypertension by enabling vascular remodeling. Obesity-associated cardiac and pulmonary conditions will increase pulmonary hypertension prevalence.

Visceral Adipose Tissue Accumulation and Residual Cardiovascular Risk.

PURPOSE OF THE REVIEW: Low-grade systemic inflammation increases residual cardiovascular risk. The pathogenesis of low-grade systemic inflammation is not well understood. RECENT FINDINGS: Visceral adipose tissue accumulates when the subcutaneous adipose tissue can no longer store excess nutrients. Visceral adipose tissue inflammation initially facilitates storage of nutrients but with time become maladaptive and responsible for low-grade systemic inflammation. Control of low-grade systemic inflammation requires reversal of visceral adipose tissue accumulation with intense and sustained aerobic exercise or bariatric surgery. Alternatively, pharmacologic inhibition of the inflammatory signaling pathway may be considered. Reversal visceral adipose tissue accumulation lowers residual cardiovascular risk.

Regression of Left Ventricular Mass After Bariatric Surgery.

Notwithstanding the presence of hypertension, obstructive sleep apnea, or both, obesity is associated with increased left ventricular (LV) mass. The effects of bariatric surgery on LV mass have been sparsely investigated by M-mode and two-dimensional (2D) echocardiography. Overall, Roux-en-Y gastric bypass, adjustable gastric banding, and sleeve gastrectomy reduce LV mass. However, the reduction in LV mass is extremely variable. Besides duration and severity of obesity, presence of hypertension, obstructive sleep apnea or both, and type of surgical procedures, the inaccuracy of M-mode and 2D echocardiography for assessment of LV mass contributes to the variable effects of bariatric surgery on LV mass. Three-dimensional (3D) echocardiography may obviate the limitations of M-mode 2D echocardiography for assessment of LV mass and allow an accurate appraisal of the effects of bariatric surgery on LV mass.

Pathophysiology and Potential Non-Pharmacologic Treatments of Obesity or Kidney Disease Associated Refractory Hypertension.

PURPOSE OF REVIEW: The review assesses the role of non-pharmacologic therapy for obesity and chronic kidney disease (CKD) associated refractory hypertension (rf HTN). RECENT FINDINGS: Hypertensive patients with markedly heightened sympathetic nervous system (SNS) activity are prone to develop refractory hypertension (rfHTN). Patients with obesity and chronic kidney disease (CKD)-associated HTN have particularly heightened SNS activity and are at high risk of rfHTN. The role of bariatric surgery is increasingly recognized in treatment of obesity. Current evidence advocates for a greater role of bariatric surgery in the management of obesity-associated HTN. In contrast, renal denervation does not appear have a role in the management of obesity or CKD-associated HTN. The role of baroreflex activation as adjunctive anti-hypertensive therapy remains to be defined.

Obesity-Associated Hypertension: the Upcoming Phenotype in African-American Women.

PURPOSE OF REVIEW: The present obesity epidemic particularly affects African-American women. Whether the obesity epidemic will alter the hypertension phenotype in African-American women is entertained. RECENT FINDINGS: The prevalence of morbid obesity is steadily increasing in African-American women, who are prone to developing hypertension (HTN) even in the absence of obesity. The obesity-associated hypertension phenotype is characterized by marked sympathetic nervous system activation and resistance/refractoriness to antihypertensive therapy. Weight loss achieved through lifestyle interventions and pharmacotherapy has a modest and rarely sustained antihypertensive effect. In contrast, bariatric surgery has a sustained antihypertensive effect, as evidenced by normalization of hypertension or lessening of antihypertensive therapy. The prevalence of HTN and its obesity-associated phenotype is likely to increase in African-American women over the next decades. Obese African-American women may be increasingly referred for bariatric surgery when hypertension remains uncontrolled despite lifestyle interventions and pharmacological therapy for weight loss and blood pressure (BP) control.

Limited role and benefit of ivabradine in the treatment of angina and heart failure with reduced ejection fraction.

Ivabradine is an original drug that has been approved in two indications (systolic heart failure and angina). The aim of this short review is to draw the attention of clinician prescribers to the evidence base of ivabradine. Three large randomized trials testing ivabradine versus placebo have been performed. The BEAUTIFUL and SIGNIFY trials were in fact negative in the treatment of angina while the SHIFT trial found a marginal benefit of ivabradine over placebo in the treatment of heart failure. These important results are put into perspective in order to improve the assessment of risk-cost/benefit balances when ivabradine is considered. Ideally, a further clinical trial investigating the use of ivabradine in heart failure should be carried out with optimal treatment of the patient population in order to identify the subgroup of patients who respond to ivabradine.

Pharmacologic and Endovascular Reversal of Left Ventricular Remodeling.

Pathologic left ventricular (LV) remodeling as described by adverse changes in LV mass, volume, geometry, and composition in response to mechanical and systemic neurohormonal activation portends a poor prognosis in patients with underlying LV systolic dysfunction. Conversely, reversal of LV remodeling is associated with improved morbidity and mortality. Improvement in LV function and size may result from either change in loading conditions or reversal of remodeling (RR). When complete normalization of LV function and geometry occurs (ejection fraction >50% and indexed LV end-diastolic dimension <33 mm/m(2)), true reversal of LV alteration is likely to have occurred. Sustained improvement in function and dimensions after therapy withdrawal further supports RR. In the absence of complete RR one cannot readily differentiate incomplete RR from changes in loading conditions. In this review, we evaluate the role of renin-angiotensin-aldosterone system inhibition, beta-adrenergic receptor blockade, cardiac resynchronization therapy, and endovascular mitral repair on LVRR and improvement in LV geometry and function.

Vascular and Microvascular Endothelial Function in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Assessment of vascular endothelial function lacks consistency, and microvascular endothelial function has been only partly assessed in heart failure with preserved ejection fraction (HFpEF). METHODS: The study population consisted of 90 patients: 45 had well documented HFpEF, and 45 had hypertension and no history or evidence of heart failure. Patients with hypertension but no heart failure were matched with HFpEF patients for age, sex, and diabetes. They served as control subjects. All patients underwent 2-dimensional Doppler echocardiography and vascular function measurements, including assessment of arterial wave reflections and arterial stiffness, brachial artery flow-mediated dilation (FMD), and forearm cutaneous blood flow with the use of a laser Doppler flow probe at rest and after release of arterial occlusion for 5 minutes. RESULTS: Brachial artery FMD was lower in HFpEF than in control subjects (median (IQR) 3.6 (0.4-7.4) vs. 7.2 (3.2-17.2)%, P = .001). Forearm cutaneous blood flow at rest was similar in HFpEF and control subjects (P = .68). After release of arterial occlusion, forearm cutaneous peak blood flow was lower in HFpEF than in control subjects (P = .03). Estimated aortic systolic and mean blood pressures were similar in HFpEF and control subjects, whereas pulse pressure and pressure augmentation were greater in HFPEF than in control subjects (both P < .05). CONCLUSION: Compared with hypertensive control subjects, patients with HFpEF had a depressed endothelial function in the forearm vasculature and microvasculature.

Challenges in the Management of Patients with Chronic Obstructive Pulmonary Disease and Heart Failure With Reduced Ejection Fraction.

Chronic obstructive pulmonary disease (COPD) and heart failure with reduced ejection fraction (HFrEF) commonly coexist in clinical practice. The prevalence of COPD among HFrEF patients ranges from 20 to 32 %. On the other hand; HFrEF is prevalent in more than 20 % of COPD patients. With an aging population, the number of patients with coexisting COPD and HFrEF is on rise. Coexisting COPD and HFrEF presents a unique diagnostic and therapeutic clinical conundrum. Common symptoms shared by both conditions mask the early referral and detection of the other. Beta blockers (BB), angiotensin-converting enzyme inhibitors, and aldosterone antagonists have been shown to reduce hospitalizations, morbidity, and mortality in HFrEF while long-acting inhaled bronchodilators (beta-2-agonists and anticholinergics) and corticosteroids have been endorsed for COPD treatment. The opposing pharmacotherapy of BBs and beta-2-agonists highlight the conflict in prescribing BBs in COPD and beta-2-agonists in HFrEF. This has resulted in underutilization of evidence-based therapy for HFrEF in COPD patients owing to fear of adverse effects. This review aims to provide an update and current perspective on diagnostic and therapeutic management of patients with coexisting COPD and HFrEF.

Toward safe inotropic therapy.

The use of currently available positive inotropic agents is associated with an unfavorable clinical outcome. The disappointment with positive inotropic therapy is to some extent foreseeable as currently available inotropic agents may precipitate ventricular arrhythmias due to a diastolic rise in intracellular [Ca], trigger/worsen myocardial ischemia due to an increased oxygen demand, and foster fuel deprivation from an energy starved heart. Safe use of presently available inotropic agents and development of novel inotropic agents must ensure that they are not associated with a diastolic rise in intracellular [Ca], an increase in myocardial oxygen consumption, and energy expenditure. Agents that improve left ventricular systolic performance through prolongation of left ventricular ejection time and not through increased myocardial contractility, that is, myosin activators, may be associated with a favorable outcome as they do not affect diastolic intracellular [Ca], myocardial oxygen demand, and presumably fuel expenditure.

Menopause, epicardial adiposity and preserved ejection fraction heart failure.

Postmenopausal women are overrepresented in the preserved ejection heart failure population. Expansion of visceral and epicardial adipose tissue during the menopause transition leads to local and low-grade systemic inflammation that in turn contributes to left ventricular concentric remodeling, diastolic dysfunction and the development and progression of preserved ejection fraction. In contrast to visceral adipose tissue imaging, epicardial adipose tissue can be inexpensively imaged on low radiation coronary calcium score computerized tomography examination. The menopause transition provides a unique time frame to evaluate the contribution of epicardial adipose tissue expansion to the pathogenesis of preserved ejection heart failure.

Mitral Annular Calcification-Related Valvular Disease: A Challenging Entity.

Mitral valve annular calcification-related valvular disease is increasingly common due to the rising prevalence of age-related mitral annular calcifications. Mitral annular calcification alters the structure and function of the mitral valve annulus, which in turn causes mitral valve regurgitation, stenosis, or both. As it frequently coexists with comorbid conditions and overlapping symptoms, mitral annular calcification-related valvular disease poses significant diagnostic and therapeutic challenges. For instance, left ventricular diastolic dysfunction hinders the assessment of mitral valvular disease. Detection of mitral annular calcifications and assessment of related mitral valve disease hinge on two-dimensional echocardiography. Comprehensive assessment of mitral annular calcifications and related mitral valve disease may require multidetector computed tomography and three-dimensional echocardiography. Invasive hemodynamic testing with exercise helps identify the cause of symptoms in patients with comorbid conditions, and transcatheter interventions have emerged as a viable therapeutic option for older patients. After an outline of the normal mitral annulus, we examine how mitral annular calcifications lead to mitral valve disease and how to accurately assess mitral regurgitation and stenosis. Lastly, we review surgical and transcatheter approaches to the management of mitral annular calcification-related mitral valve regurgitation, stenosis, or both.