July 2021 at a glance: focus on blood volume distribution, haemodynamics and adherence to therapy.

Abstract

Treatment with loop diuretics has a pivotal role in heart failure (HF) and may have an impact on outcome.1, 2 The association between loop diuretics, HF and outcome was investigated in patients with type 2 diabetes at high risk for cardiovascular (CV) events enrolled in EMPA-REG OUTCOME. Patients with both a diagnosis of HF and on loop diuretics had the highest rates of all-cause and CV mortality and HF hospitalizations. The subgroups of patients with HF and those on loop diuretics but without an investigator-reported diagnosis of HF had a similar, greater risk of all outcomes, compared with those with neither HF nor on diuretics, suggesting a possible under-diagnosis of HF and the usefulness of diuretic prescription as a surrogate for a diagnosis of HF.3 Miller et al.4 studied the relation between total blood volume (TBV), measured by radiolabel indicator-dilution methodology and haemodynamic parameters assessed by echocardiography and right heart catheterization, in 66 patients with chronic HF. Patients were divided into hypervolaemic (n = 39) or euvolaemic (n = 27), according to their TBV. Hypervolaemic patients showed higher central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) compared to the euvolaemic ones. However, 15% of hypervolaemic patients had normal right and left ventricular (LV) pressures and 70% and 63% of the euvolaemic patients had elevated CVP and PCWP, respectively. TBV, LV e', and left atrial strain were independently associated with PCWP, thus showing the major role cardiac function as determinant on filling pressure in HF.4 Congestion is a major determinant of the significance of changes in serum creatinine levels.5 Wettersten et al.6 examined the relation between improved renal function, defined by ≥20% increase in estimated glomerular filtration rate from admission, and congestion, assessed through B-type natriuretic peptide (BNP) levels, in 760 patients with acute HF. Patients with improved renal function had more severe HF with a 25% 1-year mortality, compared with a 15% in the others. However, differently from BNP, improved renal function was not an independent predictor of outcome with a similar high mortality in patients without a decrease in BNP, with or without improved renal function.6 Dauw et al.7 studied the effects of one day diuretic omission in 40 ambulatory patients with chronic HF on 40–80 mg furosemide daily. After diuretic omission, patients had a 50% drop in natriuresis and a 31% reduction in urine output, compared with the day before. The rationale for the development of a novel nytroxyl donor has been previously described.8 In a randomized, multicentre, double-blind, crossover trial, the effects of nitroxyl donor cimlanod on cardiac function were compared with those of nitroglycerin or placebo in patients with HF and reduced ejection fraction (HFrEF). Both drugs had similar effects, namely venodilatation and preload reduction, without additional inotropic or lusitropic effects.9 Cardiac contractility modulation (CCM) may improve functional capacity and reduce CV and HF hospitalizations.10, 11 Long-term effects of CCM were evaluated in a European prospective registry including 503 patients. Quality of life and LV ejection fraction (LVEF) improved, while HF hospitalizations were reduced compared to before treatment.12 Approximately 60–70% of blood volume resides in the venous circulation and up to 20–50% is in the high capacitance, highly innervated, veins of the splanchnic compartment. Sympathetic stimulation causes their constriction or shifting blood to the heart with a rise in intracardiac pressure. Splanchnic nerve modulation is proposed to inhibit such effect. It is reviewed here, and its favourable effects in a first series of patients with heart failure and preserved ejection fraction (HFpEF) on exercise PCWP and improved quality of life are reported.13, 14 Strategies to improve adherence to guideline-directed medical therapy (GDMT) are needed for patients with HFrEF.15-17 In 2345 patients with worsening HF from the BIOSTAT-CHF study, up-titration of renin–angiotensin inhibitors (RASi) and beta-blockers had beneficial effects in patients with LVEF ≤49% and ≤40%, respectively. Up-titration of beta-blockers in those with LVEF ≥50% was associated with a greater risk of HF hospitalizations.18 Gupta et al.19 used liquid chromatography-mass spectrometry in a single spot urine sample to assess non-adherence to medications in 1296 patients with worsening HF enrolled in BIOSTAT-CHF. Non-adherence to at least one prescribed medication was observed in 45.9% of patients and was associated with a 38% increased risk of all-cause death or HF hospitalization. Bhatt et al.20 showed the usefulness of a pharmacist–physician GDMT team, compared to no team, to optimize treatment during a non-CV hospitalization of patients with HFrEF. Cognitive impairment is frequent in patients with HF and may be an obstacle for adherence to therapy.21, 22 It was a major determinant of the benefits of a disease management programme on 30-day and 90-day readmission or death in 1152 consecutive patients with a recent hospitalization for HF.23 The beneficial effects of sodium–glucose co-transporter 2 inhibitors in HFrEF patients at risk for CV events are now well established.16, 24-26 Their efficacy in patients with HFpEF will be shown by the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved), whose rationale, design and baseline characteristics of the included patients were recently published,27-29 and the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure (DELIVER) trial, whose design is published in the current issue.30 Mehra et al.31 present the design of the Antiplatelet Removal and Hemocompatibility Events with the HeartMate 3 Pump (ARIES HM3) trial, a study assessing the safety and efficacy for the reduction of bleeding events of withdrawal of antiplatelet therapy in patients with a HeartMate 3 LV assist device.