Pratik Mondal

Limitations of Sacubitril/valsartan in the Management of Heart Failure

Background: The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial was a double-blind trial that randomized 8442 patients with heart failure (HF) with reduced ejection fraction (HFrEF) to receive twice daily dosing of either 200 mg of LCZ696 or 10 mg of enalapril in addition to standard medical therapy for HF. Areas of Uncertainty: Limitations of this trial include (1) sacubitril has not been tested by itself in the treatment of HFrEF; (2) the maximum recommended dose of valsartan for the treatment of HFrEF was used in this trial, but the maximum recommended dose of enalapril for the treatment of HFrEF was not used; (3) a run-in phase was used in this trial to test the tolerability of LCZ696, and patients who had adverse effects in this period were excluded from randomization; (4) the percent of blacks enrolled in this trial was only 5%; (5) LCZ696 caused a 14% incidence of hypotension; (6) neprilysin inhibition might favor the development of Alzheimer dementia, which was not assessed in the PARADIGM-HF trial; (7) patients with severe symptomatic HF were underrepresented in this trial; (8) major exclusions from this trial included an acute coronary event in the last 3 months, severe pulmonary disease, hepatic impairment, and an estimated glomerular filtration rate <30 mL per minute per 1.73 m2. Data Sources: Review of the PARADIGM-HF trial. Results: At 27-month follow-up, the PARADIGM-HF trial showed that compared with enalapril, LCZ696 reduced the composite of cardiovascular death or hospitalization for HF 20% (absolute risk reduction 4.7%, P < 0.001). Conclusions: The numerous limitations discussed under the areas of uncertainty should be considered when prescribing LCZ696 for the treatment of HFrEF.

The evolution of natriuretic peptide augmentation in management of heart failure and the role of sacubitril/valsartan

Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, and the sequence of events which led to the development of sacubitril plus valsartan (Entresto; LCZ696; Novartis). LCZ696 has been shown to be superior to the standard of care available for treatment of HFrEF in several substantial hard endpoints including heart failure hospitalizations, cardiovascular mortality, and all-cause mortality.

Cardiac papillary fibroelastoma: The need for a timely diagnosis

Cardiac papillary fibroelastomas (CPFs) are the second most common primary cardiac tumors and the most common cardiac valvular tumors. Although they are histologically benign and usually asymptomatic, CPFs can lead to serious and life-threatening complications like myocardial infarction, stroke, pulmonary embolus, cardiac arrest etc. CPFs represent a rare entity in clinical medicine and literature regarding their management is limited. We report two cases which illustrate such complications arising from undiagnosed CPFs on the aortic valve. We further stress on the importance of identifying CPFs early so that they can be managed appropriately based on recommendations from the available literature.

National Landscape of Unplanned 30-Day Readmissions in Patients with Left Ventricular Assist Device Implantation

The number of patients with advanced heart failure receiving left ventricular assist device (LVAD) implantation has increased dramatically over the last decade. There are limited data available about the nationwide trends of complications leading to readmissions after implantation of contemporary devices. Patients who underwent LVAD implantation from January 2013 to December 2013 were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 37.66 from the Healthcare Cost and Utilization Projects National Readmission Database. The top causes of unplanned 30-day readmission after LVAD implantation were determined. Survey logistic regression was used to analyze the significant predictors of readmission. In 2013, there were 2,235 patients with an LVAD implantation. Of them, 665 (29.7%) had at least 1 unplanned readmission within 30 days, out of which 289 (43.4%) occurred within 10 days after discharge. Implant complications (14.9%), congestive heart failure (11.7%), and gastrointestinal bleeding (8.4%) were the top 3 diagnoses for the first readmission and accounted for more than a third of all readmissions. Significant predictors of readmissions included a prolonged length of stay during the index admission, Medicare insurance, and discharge to short-term facility. In conclusion, despite increased experience with LVADs, unplanned readmissions within 30 days of implantation remain significantly high.

Prevalence and In-Hospital Outcomes of Uremic and Dialysis Pericarditis: A United States National Study

Background: In the modern dialysis era, uremic and dialysis pericarditis (UDP) are less frequently encountered in clinical practice. We sought to determine the secular variation and in-hospital outcomes of UDP. Methods: Using the U.S. Nationwide Inpatient Sample databases 2003 through 2012, we

IN-HOSPITAL OUTCOMES AND HOSPITALIZATIONS FOR ACUTE RHEUMATIC HEART DISEASE: A UNITED STATES NATIONAL STUDY

Background: Acute rheumatic heart disease (ARHD) is a serious manifestation of acute rheumatic fever (ARF) and can result in long-term cardiac complications. Literature suggests that the incidence of ARF is declining in the United States (US). However, the secular variation of ARHD has not been