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.

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.

Comprehensive and Safe Decongestion in Acutely Decompensated Heart Failure.

PURPOSE OF THE REVIEW: Progressive intravascular, interstitial, and alveolar fluid overload underlies the transition from compensated to acutely decompensated heart failure and loop diuretics are the mainstay of treatment. Adverse effects and resistance to loop diuretics received much attention while the contribution of a depressed cardiac output to diuretic resistance was downplayed. RECENT FINDINGS: Analysis of experience with positive inotropic agents, especially dobutamine, indicates that enhancement of cardiac output is not consistently associated with increased renal blood flow. However, urinary output and renal sodium excretion increase likely due to dobutamine-mediated decrease in renal and systemic reduced activation of sympathetic nervous- and renin-angiotensin-aldosterone system. Mechanical circulatory support with left ventricular assist devices ascertained the contribution of low cardiac output to diuretic resistance and the pathogenesis and progression of kidney disease in acutely decompensated heart failure. Diuretic resistance commonly occurs in acutely decompensated heart failure. However, failure to resolve fluid overload despite high doses of loop diuretics should alert to the presence of a low cardiac output state.

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.

Pooled diagnostic accuracy of resting distal to aortic coronary pressure referenced to fractional flow reserve: The importance of resting coronary physiology.

INTRODUCTION: Both resting and hyperemic physiologic methods to guide coronary revascularization improve cardiovascular outcomes compared with angiographic guidance alone. Fractional flow reserve (FFR) remains underutilized due to concerns regarding hyperemia, prompting study of resting distal to aortic coronary pressure (Pd/Pa). Pd/Pa is a vasodilator-free resting index unlike FFR. While Pd/Pa is similar to another resting index, instantaneous wave-free ratio (iFR), it is a whole-cycle measurement not limited to the wave-free diastolic period. Pd/Pa is not validated clinically although multiple accuracy studies have been performed. Our meta-analysis examines the overall diagnostic accuracy of Pd/Pa referenced to FFR, the accepted invasive standard of ischemia. METHODS: We searched PubMed, EMBASE, Central, ProQuest, and Web of Science databases for full text articles published through August 9, 2017 addressing the diagnostic accuracy of Pd/Pa referenced to FFR < 0.80. The following keywords were used: "distal coronary artery pressure" OR "Pd/Pa" AND "fractional flow reserve" OR "FFR." RESULTS: In total, 14 studies comprising 7004 lesions were identified. Pooled diagnostic accuracy estimates of Pd/Pa versus FFR < 0.80 were: sensitivity, 0.77 (95% CI, 0.75-0.78); specificity, 0.82 (0.81-0.83); positive likelihood ratio, 4.7 (3.3-6.6); negative likelihood ratio, 0.29 (0.24-0.34); diagnostic odds ratio, 18.1 (14.4-22.6); area under the summary receiver-operating characteristic curve of 0.88; and diagnostic accuracy of 0.80 (0.76-0.83). CONCLUSIONS: Pd/Pa shows adequate agreement with FFR as a resting index of coronary stenosis severity without the undesired effects and cost of hyperemic agents. Pd/Pa has the potential to guide coronary revascularization with easier application and availability compared with iFR and FFR.

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.

Novel Pathophysiological Mechanisms in Hypertension.

Hypertension is the most common disease affecting humans and imparts a significant cardiovascular and renal risk to patients. Extensive research over the past few decades has enhanced our understanding of the underlying mechanisms in hypertension. However, in most instances, the cause of hypertension in a given patient continues to remain elusive. Nevertheless, achieving aggressive blood pressure goals significantly reduces cardiovascular morbidity and mortality, as demonstrated in the recently concluded SPRINT trial. Since a large proportion of patients still fail to achieve blood pressure goals, knowledge of novel pathophysiologic mechanisms and mechanism based treatment strategies is crucial. The following chapter will review the novel pathophysiological mechanisms in hypertension, with a focus on role of immunity, inflammation and vascular endothelial homeostasis. The therapeutic implications of these mechanisms will be discussed where applicable.

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.

Patient-Centered Heart Failure Therapy.

Simultaneous initiation of quadruple therapy with angiotensin receptor-neprilysin inhibitor, beta-adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor aims at prompt improvement and prevention of readmission in patients hospitalized for heart failure with reduced ejection fraction. However, titration of quadruple therapy is time consuming. Lengthy up-titration of quadruple therapy may negate the benefit of early initiation. Quadruple therapy should start with a sodium glucose cotransporter 2 inhibition and a mineralocorticoid antagonist, as both enable safe decongestion and require minimal or no titration. Depending on the level of decongestion and clinical characteristics, patients receive an angiotensin receptor-neprilysin inhibitor or a beta-adrenergic receptor blocker to be titrated after hospital discharge. Outpatient addition of an angiotensin receptor-neprilysin inhibitor to a beta-adrenergic receptor blocker or vice versa completes the quadruple therapy scheme. By focusing on decongestion and matching intervention to patients' profile, the present therapeutic sequence allows rapid implementation of quadruple therapy at fully recommended doses.

Clinical utility of natriuretic peptides in left ventricular failure.

Left ventricular failure (LVF) is a clinical syndrome caused by abnormal systolic or diastolic function failing to meet the metabolic requirements of the body. It is important to diagnose and manage LVF in the earliest stages to prevent mortality and morbidity. This article extensively reviews the diagnostic, therapeutic, and prognostic utility of natriuretic peptides in LVF.

Myocardial recovery following left ventricular assist device implantation.

Durable left ventricular assist devices (LVADs) have consistently shown improved mortality and morbidity in patients with end-stage heart failure. Select patients with LVADs may experience significant enough myocardial recovery after device implantation to allow for explantation or decommissioning. While earlier trials suggested a high incidence of recovery, real-world clinical data have demonstrated this to be a much rarer phenomenon. Whether or not patients experience recovery, practices such as speed optimization and usage of guideline-directed medical therapy can improve patient outcomes.

Therapeutic Stalemate in Heart Failure With Preserved Ejection Fraction.

The findings of randomized trials of neurohormonal modulation have been neutral in heart failure with preserved ejection fraction and consistently positive in heart failure with reduced ejection. Left ventricular remodeling promotes the development and progression of heart failure with preserved and reduced ejection fraction. However, different stimuli mediate left ventricular remodeling that is commonly concentric in heart failure with preserved ejection fraction and eccentric in heart failure with reduced ejection. The stimuli that promote concentric left ventricular remodeling may account for the neutral findings of neuhormonal modulation in heart failure with preserved ejection fraction. Low-grade systemic inflammation-induced microvascular endothelial dysfunction is currently the leading hypothesis behind the development and progression of heart failure with preserved ejection fraction. The hypothesis provided the rationale for several randomized controlled trials that have led to neutral findings. The trials and their limitations are reviewed.

Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction: Role of Obesity.

Heart failure with preserved ejection fraction is a growing epidemic and accounts for half of all patients with heart failure. Increasing prevalence, morbidity, and clinical inertia have spurred a rethinking of the pathophysiology of heart failure with preserved ejection fraction. Unlike heart failure with reduced ejection fraction, heart failure with preserved ejection fraction has distinct clinical phenotypes. The obese-diabetic phenotype is the most often encountered phenotype in clinical practice and shares the greatest burden of morbidity and mortality. Left ventricular remodeling plays a major role in its pathophysiology. Understanding the interplay of obesity, diabetes mellitus, and inflammation in the pathophysiology of left ventricular remodeling may help in the discovery of new therapeutic targets to improve clinical outcomes in heart failure with preserved ejection fraction. Anti-diabetic agents like glucagon-like-peptide 1 analogs and sodium-glucose co-transporter 2 are promising therapeutic modalities for the obese-diabetic phenotype of heart failure with preserved ejection fraction and aggressive weight loss via lifestyle or bariatric surgery is still key to reverse adverse left ventricular remodeling. This review focuses on the obese-diabetic phenotype of heart failure with preserved ejection fraction highlighting the interaction between obesity, diabetes, and coronary microvascular dysfunction in the development and progression of left ventricular remodeling. Recent therapeutic advances are reviewed.