Heart failure (HF) continues to be a major global health problem with a notable impact in terms of morbidity and mortality and so, in consequence, with a large unmet necessity for new therapies. The inhibition of sodium-glucose cotransporter 2 (SGLT2) causes glycosuria and natriuresis, leading to reductions in hyperglycemia (antidiabetic effect), body weight, and blood pressure. In this context, outcome trials have been shown to reduce hospitalizations for HF in patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. The underlying protective cardiovascular (CV) mechanisms of these agents are complex, multifactorial, and not entirely understood as, in addition to a diuretic-like function, SGLT2 inhibitors may mitigate glycemic-related toxicity, promote ketogenesis, increase hematocrit, and exert antihypertrophic, antifibrotic, and antiremodeling properties. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled 4744 patients with HF and reduced ejection fraction (EF) who were receiving excellent guideline-directed treatment before the addition of dapagliflozin (a SGLT2 inhibitor) or placebo. The DAPA-HF trial clearly showed that dapagliflozin was superior to placebo at preventing CV deaths and HF events. The relative and absolute risk reductions in death and hospitalizations were consistent across subgroups including patients with and without diabetes; so, in consequence, dapagliflozin represents the first in a new class of drug for HF with reduced EF. The recently published Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction (DEFINE-HF) trial is also described in this review as well as the thought-to-be mechanisms of action of SGLT2 inhibitors beyond their known glucose-lowering effects. There is a vast, ambitious, and promising ongoing clinical investigation program with dapagliflozin and other SGLT2 inhibitors, which may result in changes to the therapeutic approach to HF in a relatively short time.
19 October 2016 in Therapeutic Advances in Chronic Disease
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release). Results from the 8442 patient PARADIGM-HF study showed in patients with New York Heart Association (NYHA) class II–IV and reduced ejection fraction treated with LCZ696 (versus enalapril), the following benefits: reduction of the risk of death from cardiovascular causes by 20%; reduction of HF hospitalizations by 21%; reduction of the risk of all-cause mortality by 16%. Overall there was a 20% risk reduction on the primary endpoint, composite measure of cardiovascular (CV) death or time to first HF hospitalization. PARADIGM-HF was stopped early after a median follow up of 27 months. Post hoc analyses of PARADIGM-HF as well as the place in therapy of sacubitril/valsartan, including future directions, are included in the present review.
Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic infections, dengue fever, and a severe form called hemorrhagic dengue or dengue shock syndrome. Atypical manifestations can also occur, called expanded dengue syndrome. We describe the case of a 43-year-old man with an unusual presentation of dengue, demonstrating a workup suggestive of myocardial and pericardial damage. Symptoms and markers indicative of cardiac compromise improved after five days on anti-inflammatory treatment. Dengue myocarditis is considered an uncommon complication of dengue, although its reported incidence is likely an underestimation. In general, most cases of dengue myocarditis are self-limited, with only a minority at risk of progressing to heart failure. In order to improve recognition and prevent progression, healthcare providers should maintain a high degree of suspicion regarding potential cardiac complications in patients with dengue.
This article reviews point-of-care ultrasound (POCUS) application in the emergency department or the intensive care unit, focused on severely compromised patients with cardiogenic shock with an emergent bedside assessment.
Background: Obstructive sleep apnea (OSA) is strongly associated with obesity, and weight loss is a cornerstone of its management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are a class of medications that induce significant weight loss and have shown promise in improving OSA severity. Purpose: This meta-analysis aimed to evaluate the pooled efficacy of GLP-1 RAs on sleep-disordered breathing, body weight, and cardiovascular risk factors in patients with OSA. Methods: A systematic review and meta-analysis of four randomized controlled trials were performed, comparing GLP-1 RA therapy with placebo in adults with OSA. The primary outcomes analyzed were the mean differences in the change from baseline for the apnea-hypopnea index (AHI), body weight, and systolic and diastolic blood pressure. Results: In the pooled analysis, treatment with GLP-1 RAs was associated with a robust and statistically significant reduction in AHI (mean difference [MD]: -13.89 events/hour; p < 0.01). Therapy also resulted in substantial weight loss compared to placebo (MD: -12.46 kg; p < 0.01). For cardiovascular parameters, the use of GLP-1 RA was associated with a significant reduction in systolic blood pressure (mean difference [MD]: -4.86 mmHg; p < 0.01) and diastolic blood pressure ( p = 0.03). Conclusion: GLP-1 receptor agonists significantly reduce OSA severity, promote substantial weight loss, and lower systolic and diastolic blood pressure in patients with obstructive sleep apnea and obesity. These findings support the role of GLP-1 RAs as a multifaceted and effective therapeutic intervention for managing OSA.