Loop diuretics remain the cornerstone of decongestion in acute heart failure, yet their use in heart failure with reduced ejection fraction (HFrEF) is obscured by two competing errors: undertreating congestion because serum creatinine rises, and continuing or escalating diuretics after euvolaemia. This narrative review integrates established evidence and contemporary guidance into a phase-based cardiorenal decision framework. Congestion is framed as a continuum generated by sodium retention, redistribution of stressed blood volume, vascular and ventricular compliance, right-sided pressure, and renal sodium avidity—not as a binary distinction between pressure and volume overload. During acute decompensation, intravenous loop diuretics remain first-line therapy; early urine output and spot urinary sodium can identify inadequate response and support protocolized escalation. Acetazolamide or a thiazide-type diuretic can improve decongestion when loop response is insufficient, although renal and electrolyte surveillance is essential. Sodium–glucose cotransporter 2 inhibitors should be initiated for disease modification after stabilization, but their context-dependent natriuretic effect does not replace loop diuretics in marked congestion. A creatinine rise during effective decongestion should be interpreted with residual congestion, haemodynamics, urine output, electrolytes, and evidence of kidney injury rather than through a universal threshold. After stabilization, implementation of foundational HFrEF therapy and reassessment of the minimum effective loop dose become priorities. Studies suggest that dose reduction or withdrawal is feasible in stable, euvolaemic patients, but event-powered evidence and validated outpatient biomarkers are lacking. Diuretics and disease-modifying therapy therefore have complementary, time-dependent roles: remove sodium when congestion is present, protect the kidney while recognizing hypoperfusion and intrinsic kidney injury, and de-escalate only after euvolaemia.
Subcutaneous (SC) furosemide offers an outpatient option for decongestion in chronic heart failure (HF) patients who remain symptomatic on oral diuretics or who would otherwise require recurrent intravenous (IV) therapy. Furoscix, the only FDA-approved SC furosemide, delivers 80 mg over 5 hours via an on-body infusor with pharmacokinetics and diuretic effects comparable to IV dosing. In this primer, we summarize the evidence supporting SC furosemide and share our institutional experience implementing it in a multidisciplinary ambulatory HF clinic, where it has now been prescribed to more than 75 patients. We argue that successful adoption depends less on the drug itself than on the workflows—patient selection, prescribing logistics, education, and post-administration monitoring—built around it, and we outline emerging opportunities to extend SC furosemide to advanced HF, hospital discharge, and emergency department transitions.
The composite of cardiovascular or all-cause death and worsening heart failure (WHF) has become the principal efficacy endpoint of heart failure trials. Yet WHF is not one event: it spans outpatient oral-diuretic escalation, urgent intravenous-diuretic visits, hospitalisation, and HF-related death—tiers that differ markedly in frequency, ascertainment, and prognostic weight. A composite WHF benefit therefore cannot be properly interpreted without knowing which tier carries the signal, and we argue that this tier is both phenotype- and setting-dependent. Two trials published on the same day in 2026 make the point with unusual clarity. In the Dig-RHD trial of digoxin in rheumatic heart disease, the benefit concentrated in outpatient diuretic events, with neutral results at hospitalisation and death; in a contemporaneous meta-analysis of digitalis glycosides in reduced or mildly reduced ejection fraction, the same drug class reduced worsening heart failure mainly through hospitalisation, again without a mortality benefit. We use this contrast to propose a severity-gradient framework for reporting and interpreting worsening heart failure, and discuss its implications for trial design, for the translation of guideline-based evidence across health systems, and for the use of inexpensive therapies such as digoxin in low- and middle-income settings.
In acute heart failure (AHF), non-invasive ventricular-arterial coupling (VAC) surrogates, including right ventricular-pulmonary arterial (RV-PA) and left ventricular-arterial (LV-Ao) coupling, have emerged as practical bedside indices, but their prognostic significance remains largely unknown systematically. We performed a systematic review and meta-analysis to evaluate the prognostic significance of non-invasive VAC assessment, in patients hospitalized with AHF. Outcomes included all-cause mortality, HF hospitalization, length of hospital stay, use of therapies, the composite of all-cause mortality and HF hospitalization, and in-hospital adverse cardiovascular events. Adjusted hazard ratios (aHRs) and odds ratios (aORs) were pooled using random-effects. Subgroup-analyses were performed according to follow-up duration and left ventricular ejection fraction. Thirty-six studies comprising 36,989 patients were analysed. Twenty-eight studies evaluated RV-PA coupling, predominantly the TAPSE/PASP ratio, and eight evaluated LV-Ao coupling, mainly using non-invasive Ea/Ees estimates. RV-PA uncoupling was independently associated with increased all-cause mortality (aHR 1.90; 95
Congestion remains a major therapeutic target in heart failure (HF), despite advances in guideline-directed medical therapy. Tolvaptan, a selective vasopressin V2 receptor antagonist, promotes electrolyte-sparing free-water excretion and therefore offers a mechanistically distinct approach to decongestion. Randomized trials have generally shown short-term increases in urine output and reductions in body weight, whereas effects on dyspnea and other congestion-related symptoms have been variable; importantly, no reduction in mortality or HF hospitalization has been established. This evidence has led to divergent clinical positioning: tolvaptan is approved in Japan for fluid retention inadequately controlled by other diuretics, whereas the United States and Europe do not approve it for HF congestion. This review critically summarizes the pharmacology, clinical evidence, and regional regulatory context of tolvaptan in HF. It then presents a conceptual two-stage framework incorporating potential pretreatment and early-response markers to inform patient selection, with particular attention to urine osmolality and emerging pathway-based biomarkers. The complementary roles of oral and intravenous formulations and evidence in selected clinical settings are also discussed. Current data support tolvaptan as a monitored adjunct for selected patients, not as routine therapy or a treatment with established prognostic benefit.
