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.

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.

Obesity, Preserved Ejection Fraction Heart Failure, and Left Ventricular Remodeling.

Owing to the overwhelming obesity epidemic, preserved ejection fraction heart failure commonly ensues in patients with severe obesity and the obese phenotype of preserved ejection fraction heart failure is now commonplace in clinical practice. Severe obesity and preserved ejection fraction heart failure share congruent cardiovascular, immune, and renal derangements that make it difficult to ascertain whether the obese phenotype of preserved ejection fraction heart failure is the convergence of two highly prevalent conditions or severe obesity enables the development and progression of the syndrome of preserved ejection fraction heart failure. Nevertheless, the obese phenotype of preserved ejection fraction heart failure provides a unique opportunity to assess whether sustained and sizeable loss of excess body weight via metabolic bariatric surgery reverses the concentric left ventricular remodeling that patients with preserved ejection fraction heart failure commonly display.

Early Mechanical Circulatory Support for Cardiogenic Shock.

Reversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes cardiogenic shock is a crucial step in its early detection. Treatment of pre-cardiogenic shock is chiefly pharmacologic with intravenous administration of pressor, inotropic, and loop diuretic agents. Failure to reverse the preshock state with pharmacotherapy entails progression to cardiogenic shock and the need for prompt mechanical circulatory support with membrane oxygenation and possibly left ventricular decompression.

Therapeutic Dilemmas in Mixed Septic-Cardiogenic Shock.

Sepsis is an increasing cause of decompensation in patients with chronic heart failure with reduced or preserved ejection fraction. Sepsis and decompensated heart failure results in a mixed septic-cardiogenic shock that poses several therapeutic dilemmas: Rapid fluid resuscitation is the cornerstone of sepsis management, while loop diuretics are the main stay of decompensated heart failure treatment. Whether inotropic therapy with dobutamine or inodilators improves microvascular alterations remains unsettled in sepsis. When to resume loop diuretic therapy in patients with sepsis and decompensated heart failure is unclear. In the absence of relevant guidelines, we review vasopressor therapy, the timing and volume of fluid resuscitation, and the need for inotropic therapy in patients who, with sepsis and decompensated heart failure, present with a mixed septic-cardiogenic shock.

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.

COVID 19 in-hospital mortality, body mass index and obesity related conditions.

OBJECTIVE: Obese patients with respiratory failure need more intensive care and invasive mechanical ventilation than their non-obese counterparts. We aimed to evaluate the impact of body mass index and obesity related conditions on fatal outcome during a hospitalization for COVID-19. METHODS: From March 1 to April 30, 2020, 425 consecutive patients with severe acute respiratory syndrome coronavirus 2 were hospitalized at University Medical Center, in New Orleans. Clinical variables, comorbidities, and hospital course were extracted from electronic medical records. Special attention was given to obesity related conditions like hypertension, type 2 diabetes, and dyslipidemia. Severe obesity was defined as a body mass index ≥35-<40 kg/m2 and morbid obesity as body mass index ≥40 kg/m2. Risk of mortality was determined by applying multivariate binary logistic regression modeling to risk factor variables (age, sex, race, and Charlson comorbid score). RESULTS: Patients were mostly African American (77.9%) and 51.0% were women. Age and Charlson comorbidity index scores averaged 60 (50-71 years) and 3.0 (1.25-5), respectively. In-hospital mortality was greater in morbidly obese than non-morbidly obese patients. Of the 64 severely obese patients, 16 had no obesity related conditions, and 48 had at least one obesity related condition: hypertension (60%), type 2 diabetes mellitus (28%), and dyslipidemia (20%). In-hospital mortality was greater in severely obese patients with than without at least one obesity related condition. CONCLUSION: During a hospitalization for COVID-19, severely obese patients with at least one obesity related condition and morbidly obese patients have a high mortality.

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.

Watchful waiting care or early intervention in asymptomatic severe aortic stenosis: Where we are.

Aortic stenosis, the most common valvular heart disease in Western countries, affects predominantly older people. Prompt aortic valve replacement is undoubtedly indicated in symptomatic patients. Management of asymptomatic patients is nowadays shifting from a conservative approach to early aortic valve replacement, as multimodality imaging is increasingly available. However, multimodality imaging has led to multiple prognostic parameters and complex algorithms, as well as a new staging classification that has left patients and physicians somewhat puzzled. We highlight the value of thorough serial clinical examinations, Doppler echocardiography and exercise testing when caring for a growing aortic stenosis population, including that has no or limited access to multimodality imaging. Evidence for early aortic valve replacement versus conservative management in asymptomatic patients with severe aortic stenosis is biased by the lack of serial stress testing evaluation; 30% of so-called asymptomatic patients were in fact symptomatic, and thus were clear candidates for aortic valve replacement in the above-mentioned studies. Randomized trials of aortic valve replacement versus conservative management that include serial stress testing evaluation are needed to ascertain whether early aortic valve replacement actually improves clinical outcome in asymptomatic patients with severe aortic stenosis. Less interventional medicine and healthcare resource utilization can result in better health.

Altered Mental Status and Hyponatremia After 20 Hours of Amiodarone Therapy.

A 66-year-old woman with no relevant medical history presented at the emergency department with new-onset atrial fibrillation. We initiated intravenous amiodarone therapy. At 20 hours, the patient experienced severe neurologic symptoms, hyponatremia, and syndrome of inappropriate antidiuretic hormone. We discontinued amiodarone, infused saline solution, and restricted the patient's fluid intake. She recovered in 3 days. This case illustrates that amiodarone-induced syndrome of inappropriate antidiuretic hormone with hyponatremia can occur far earlier than expected during acute amiodarone therapy.

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.