Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial.

AIM: The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown. METHODS AND RESULTS: Between 1 and 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR >20 ml/min/1.73 m2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 ml/min/1.73 m2 in the empagliflozin group and 55.7 ml/min/1.73 m2 in the placebo group. Empagliflozin caused an initial decline in eGFR (-2 ml/min/1.73 m2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator-reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all-cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR. CONCLUSION: In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function.

Heart Failure Spending Function: An Investment Framework for Sequencing and Intensification of Guideline-Directed Medical Therapies.

Heart failure with reduced ejection fraction is managed with increasing numbers of guideline-directed medical therapies (GDMT). Benefits tend to be additive. Burdens can also be additive. We propose a heart failure spending function as a conceptual framework for tailored intensification of GDMT that maximizes therapeutic opportunity while limiting adverse events and patient burden. Each patient is conceptualized to have reserve in physiological and psychosocial domains, which can be spent for a future return on investment. Key domains are blood pressure, heart rate, serum creatinine, potassium, and out-of-pocket costs. For each patient, GDMT should be initiated and intensified in a sequence that prioritizes medications with the greatest expected cardiac benefit while drawing on areas where the patient has ample reserves. When reserve is underspent, patients fail to gain the full benefit of GDMT. Conversely, when a reserve is fully spent, addition of new drugs or higher doses that draw upon a domain will lead to patient harm. The benefit of multiple agents drawing upon varied physiological domains should be balanced against cost and complexity. Thresholds for overspending are explored, as are mechanisms for implementing these concepts into routine care, but further health care delivery research is needed to validate and refine clinical use of the spending function. The heart failure spending function also suggests how newer therapies may be considered in terms of relative value, prioritizing agents that draw on different spending domains from existing GDMT.

The Association Between Secondhand Smoke Exposure and Survival for Patients With Heart Failure.

BACKGROUND: The effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF. METHODS: Nonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling. RESULTS: Mortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08-1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22-1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02-2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71-4.99, P < .001) were also associated with mortality. CONCLUSIONS: SHS exposure is associated with a dose-dependent increase in mortality for patients with HF.

Palliative Care in Heart Failure: What Triggers Specialist Consultation?

Heart failure (HF) continues to cause substantial death and suffering despite the availability of numerous medical, surgical, and technological therapeutic advancements. As a patient-centered holistic discipline focused on improving quality of life and decreasing anguish, palliative care (PC) has a crucial role in the care of HF patients that has been acknowledged by multiple international guidelines. PC can be provided by all members of the HF care team, including but not limited to practitioners with specialty PC training. Unfortunately, despite recommendations to routinely include PC techniques and providers in the care of HF patients, use of general PC strategies as well as expert PC consultation is limited by a dearth of evidence-based interventions in the HF population and knowledge as to when to initiate these interventions, uncertainty regarding patient desires, prognosis, and the respective roles of each member of the care team, and a general shortage of specialist PC providers. This review seeks to provide guidance as to when to employ the limited resource of specialist PC practitioners, in combination with services from other members of the care team, to best tend to HF patients as their disease progresses and eventually overcomes.

Shiga toxin 2 targets the murine renal collecting duct epithelium.

Hemolytic-uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli infection is a leading cause of pediatric acute renal failure. Bacterial toxins produced in the gut enter the circulation and cause a systemic toxemia and targeted cell damage. It had been previously shown that injection of Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS) caused signs and symptoms of HUS in mice, but the mechanism leading to renal failure remained uncharacterized. The current study elucidated that murine cells of the glomerular filtration barrier were unresponsive to Stx2 because they lacked the receptor glycosphingolipid globotriaosylceramide (Gb(3)) in vitro and in vivo. In contrast to the analogous human cells, Stx2 did not alter inflammatory kinase activity, cytokine release, or cell viability of the murine glomerular cells. However, murine renal cortical and medullary tubular cells expressed Gb(3) and responded to Stx2 by undergoing apoptosis. Stx2-induced loss of functioning collecting ducts in vivo caused production of increased dilute urine, resulted in dehydration, and contributed to renal failure. Stx2-mediated renal dysfunction was ameliorated by administration of the nonselective caspase inhibitor Q-VD-OPH in vivo. Stx2 therefore targets the murine collecting duct, and this Stx2-induced injury can be blocked by inhibitors of apoptosis in vivo.