Jalaj Garg

Exercise Training in Patients With Heart Failure and Preserved Ejection Fraction Meta-Analysis of Randomized Control Trials

Background—Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life, and diastolic function in patients with HFPEF. Methods and Results—Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Effect of exercise training on quality of life (estimated using Minnesota living with heart failure score), and left ventricular systolic and diastolic function was also assessed. The study included 276 patients who were enrolled in 6 randomized controlled trials. In the pooled data analysis, patients with HFPEF undergoing exercise training had significantly improved CRF (mL/kg per min; weighted mean difference, 2.72; 95% confidence interval, 1.79–3.65) and quality of life (weighted mean difference, −3.97; 95% confidence interval, −7.21 to −0.72) when compared with the control group. However, no significant change was observed in the systolic function (EF−weighted mean difference, 1.26; 95% confidence interval, −0.13% to 2.66%) or diastolic function (E/A−weighted mean difference, 0.08; 95% confidence interval, −0.01 to 0.16) with exercise training in patients with HFPEF. Conclusions—Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function.

Exercise Training in Patients with Heart Failure and Preserved Ejection Fraction: A Meta-analysis of Randomized Control Trials

Background—Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life, and diastolic function in patients with HFPEF. Methods and Results—Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Effect of exercise training on quality of life (estimated using Minnesota living with heart failure score), and left ventricular systolic and diastolic function was also assessed. The study included 276 patients who were enrolled in 6 randomized controlled trials. In the pooled data analysis, patients with HFPEF undergoing exercise training had significantly improved CRF (mL/kg per min; weighted mean difference, 2.72; 95% confidence interval, 1.79–3.65) and quality of life (weighted mean difference, −3.97; 95% confidence interval, −7.21 to −0.72) when compared with the control group. However, no significant change was observed in the systolic function (EF−weighted mean difference, 1.26; 95% confidence interval, −0.13% to 2.66%) or diastolic function (E/A−weighted mean difference, 0.08; 95% confidence interval, −0.01 to 0.16) with exercise training in patients with HFPEF. Conclusions—Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function.

Hyperkalemia among hospitalized patients and association between duration of hyperkalemia and outcomes.

Introduction The aim of the study was to investigate predictors of mortality in patients hospitalized with hyperkalemia. Material and methods Data among hospitalized patients with hyperkalemia (serum potassium ≥ 5.1 mEq/l) were collected. Patients with end-stage renal disease on dialysis were excluded. Results Of 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred in 408 patients. In patients with hyperkalemia, chronic kidney disease, hypertension, diabetes, coronary artery disease and heart failure were common comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common metabolic abnormalities, and 359 patients (88%) were on at least one drug associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12 ±9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77), and AKI (HR = 0.77) were significant independent determinants of duration prior to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and prolonged duration of hyperkalemia (OR = 1.06) were significant independent predictors of in-hospital mortality. Conclusions Tissue necrosis, potassium supplementation, metabolic acidosis, calcium gluconate for treatment of hyperkalemia, AKI and prolonged duration of hyperkalemia are independent predictors of in-hospital mortality.

Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

Background There has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta‐analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF. Methods & Results Randomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e’, a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy‐terminal peptide of procollagen type I [PICP] and amino‐terminal peptide of pro‐collagen type‐II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e’ (weighted mean difference [WMD] [95% confidence interval {CI}]: −1.68 [−2.03 to −1.33]; P<0.0001) and deceleration time (WMD [95% CI]: −12.0 ms [−23.3 to −0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions. Conclusion MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.

PCSK9 Inhibitors: A New Era of Lipid Lowering Therapy.

Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.

National Trends in Utilization, Mortality, Complications, and Cost of Care After Left Ventricular Assist Device Implantation From 2005 to 2011

BACKGROUND Left ventricular assist devices (LVADs) have shown survival benefit in end-stage heart failure patients. LVAD technology has evolved considerably with the development of continuous-flow devices. METHODS The Nationwide Inpatient Sample was queried from 2005 to 2011 using International Classification of Diseases, 9th Edition procedure code 37.66, Insertion of Implantable Heart System, in any procedure field. Patients with primary diagnosis of orthotopic heart transplant or use of temporary mechanical circulatory support devices were excluded. Procedural complications were identified using International Classification of Diseases, 9th Edition codes and patient safety indicators. Cochran-Armitage and Cuzick tests for trend were used to identify time trends for categorical and continuous variables, respectively. RESULTS There were 2,038 LVAD implantations from 2005 to 2011. LVAD use increased from 127 procedures in 2005 to 506 procedures in 2011, and in-hospital mortality declined from 47.2% to 12.7% (p < 0.001), with sharp inflection points in the year 2008. Average length of stay decreased from 44 days in the pulsatile-flow era (2005 to 2007) to 36 days in the continuous-flow era (2008 to 2011). Cost of hospitalization increased from

Peripartum cardiomyopathy: definition, incidence, etiopathogenesis, diagnosis, and management.

194,380 in 2005 to

Predictors of Coronary Artery Disease in Patients with Behçet's Disease

234,808 in 2011 but remained constant from 2008 to 2011. There was a trend of increased incidence of major bleeding and thromboembolism and decreased incidence of infectious and iatrogenic cardiac complications in the continuous-flow era. CONCLUSIONS LVAD use has increased and in-hospital mortality and LOS after LVAD implantation have declined. These changes coincide with United States Food and Drug Administration (FDA) approval of continuous-flow devices in 2008.

Epidemiology and outcomes of peripartum cardiomyopathy in the United States: findings from the Nationwide Inpatient Sample

Peripartum cardiomyopathy (PPCM) is a serious pregnancy-associated disorder of unknown etiology. The precise cellular and molecular mechanisms underlying PPCM are unclear. A heightened awareness among health care providers can result in early diagnosis of heart failure in late pregnancy and the early postpartum period. Though the symptoms of dyspnea and fatigue can result from normal physiologic changes during pregnancy, an electrocardiogram and brain natriuretic peptide level should be obtained in these patients, in addition to baseline laboratory tests such as a complete blood count, and basic metabolic and hepatic function panels. If the electrocardiogram and brain natriuretic peptide level are abnormal, an echocardiogram should be obtained. The role of endomyocardial biopsy for the diagnosis of PPCM is controversial. Patients should be started on diuretics if volume overloaded, and beta-blockers (preferably metoprolol) if no contraindications exist; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy or lactation. There are no standard, universally accepted guidelines for the management of PPCM. Although experimental therapies like bromocriptine, pentoxifylline and immunoglobulins have shown promising results, large double-blind randomized trials are essential to confirm the results of smaller studies. In patients with persistent severe left ventricular (LV) dysfunction, advanced therapies like mechanical circulatory support and heart transplantation should be considered. Owing to recent data demonstrating deterioration of LV systolic function after initial recovery, it is essential to maintain long-term follow up of these patients regardless of initial recovery of LV function. We present a comprehensive review of the literature etiopathogenesis, diagnosis, and management of PPCM.

Impact of Annual Hospital Volume on Outcomes after Left Ventricular Assist Device (LVAD) Implantation in the Contemporary Era

Background: Behçets disease (BD) is a multisystem vasculitis of unknown etiology. We aimed to determine the prevalence and predictors of coronary artery disease (CAD) in patients with BD. Methods: All adult patients diagnosed with BD from the National Inpatient Sample database using the International Classification of Diseases 9th revision (ICD-9 code 136.1) during 2009-2010 were included in the analysis. We analyzed the demographics, traditional risk factors, prevalence, and predictors of CAD in patients with BD using ICD-9 codes. Results: The prevalence of BD among adults was 0.006% (n = 2,540) of all in-hospital admissions in the USA. The mean age was 43.9 years, with women (45 years) being older than men (40 years) (p < 0.001). Traditional risk factors prevalent in our study were hypertension (35%), hyperlipidemia (17.4%), diabetes mellitus (13.8%), smoking (13.1%), and obesity (7.2%). The prevalence of CAD was 12.1%. Hypertension (OR = 2.20, p = 0.03) and hyperlipidemia (OR = 2.34, p = 0.02) were found to be independent predictors of CAD in a multimodel regression analysis. Conclusion: In patients with BD, traditional risk factors associated with CAD were similar to what is expected in the overall population. However, the young age of patients with CAD in this population suggests an accelerated course of atherosclerosis in BD.