End-stage hypertrophic cardiomyopathy (ES-HCM) presents on a spectrum between the classic left ventricular systolic dysfunction and a less-recognised, restrictive phenotype with small-to-normal-sized left ventricular cavity and preserved ejection fraction. Relatively poor prognoses follow those on this morpho-functional spectrum, marked by low cardiac output and high arrhythmic risk. Contemporary guideline-directed therapies, such as ICDs, CRT and cardiac transplantation, have significantly improved outcomes, reshaping the natural history of ES-HCM. Meanwhile, the roles of neurohormonal modulation and left ventricular assist devices remain less well defined. Still, timely recognition and intervention remain essential in patients with ES-HCM, given its considerable morbidity and mortality. As cardiac myosin inhibitors and anti-fibrotic strategies advance, early targeted treatment may modify the natural history of hypertrophic cardiomyopathy, leading to a reduction in the incidence of ES-HCM. Moving forward, broader adoption of phenotype-specific approaches and equitable application of advanced therapies are critical to address the rare but clinically significant burden of ES-HCM.

Since the discovery of natriuretic peptides in the 1980s, initially as A-type natriuretic peptide, followed by B-type natriuretic peptide, their measurement has become standard in the management of heart failure (HF), as levels are markedly elevated in patients with HF. However, systematic reviews conducted in this area have yielded inconclusive results. Position and consensus papers on natriuretic peptides and HF have uniformly adopted the paradigm that myocardial stretch is the underlying mechanism explaining elevated circulating natriuretic peptide levels. Although mechanical stress is the primary factor determining myocardial oxygen consumption, this relationship has not been studied in HF. Biological evolution has developed a specific hypoxia-sensitive pathway in which a nuclear transcription factor, hypoxia-inducible factor, serves as the oxygen sensor, enabling myocardial cells to respond to reduced oxygen tension. In myocardial cell cultures, hypoxia was found to be a direct and sufficient stimulus for the expression of natriuretic peptides via the hypoxia-inducible factor pathway. Myocardial oxygen metabolism, which regulates plasma natriuretic peptide levels, presents a new objective for clinical research in HF.

The renin–angiotensin–aldosterone system is integral to cardiorenal health, with aldosterone controlling fluid balance, blood pressure and cardiac remodelling. Despite the widespread use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists, ‘aldosterone escape’ persists, contributing to treatment failure and adverse outcomes. Steroidal mineralocorticoid receptor antagonists also cause hyperkalaemia and anti-androgenic effects, limiting their use. Aldosterone synthase inhibitors (ASIs) selectively block cytochrome P450 11B2, reducing pathological aldosterone levels while preserving basal mineralocorticoid receptor activity, thus potentially lowering hyperkalaemia risk. This narrative review identified 41 relevant publications from a PubMed/MEDLINE search of “aldosterone synthase inhibitor” through 11 January 2025. Early clinical trials of ASIs (baxdrostat, lorundrostat, vicadrostat, dexfadrostat phosphate, JX09) report significant reductions in aldosterone, blood pressure and albuminuria, with promising safety. Challenges include ensuring high selectivity, mitigating hyperkalaemia and establishing long-term benefits. Ongoing Phase III trials will clarify their efficacy, safety and synergy with additional therapies – including sodium–glucose cotransporter 2 inhibitors – and clinical outcomes, positioning ASIs as an important advance in renin–angiotensin–aldosterone system modulation.

Background:Weaning and tracheal extubation of patients after vascular surgery is a stressful procedure that triggers the sympathetic nervous system, potentially leading to deterioration of cardiac performance in patients with left ventricular dysfunction. This study compared the efficacy and safety of landiolol, a novel ultra-short-acting β1-adrenoceptor antagonist, with that of esmolol in terms of the cardiovascular response during the extubation of patients with reduced ejection fraction (EF) admitted to the intensive care unit after major vascular surgery.Methods:This single-centre, prospective, randomised, open-label study included postoperative patients with cardiac dysfunction. Patients were randomly assigned to either landiolol or esmolol. Landiolol and esmolol infusions began as soon as the respiratory weaning procedure started, and were initiated at doses of 1 and 50 µg/kg/min, respectively (up to 10 and 200 µg/kg/min, respectively). Heart rate, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure (MAP) and cardiac rhythm were recorded every minute up to 30 minutes after extubation.Results:Thirty-nine patients with cardiac dysfunction (mean [±SD] left ventricular EF 36.6 ± 7.6%; New York Heart Association Class II/III, 32/9) were infused with either landiolol (n=19; mean rate 2.0 ± 2.1 μg/kg/min) or esmolol (n=20; mean rate 150 ± 50 μg/kg/min). Mean age, left ventricular EF, New York Heart Association class and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were similar between the two groups. Landiolol produced a more rapid and substantial decrease in heart rate than esmolol (-40 ± 20 BPM versus -30 ± 16 BPM) without haemodynamic deterioration. A significant reduction in MAP was recorded in the esmolol group.Conclusion:Landiolol produced a more rapid and potent reduction in heart rate than esmolol. A significant reduction in MAP was only seen in the esmolol group.

The concept of heart failure (HF) has undergone significant transformation from ancient times to the present, evolving from rudimentary understandings to a complex clinical syndrome. Early descriptions by Egyptian, Greek and Roman physicians laid the groundwork for understanding cardiac dysfunction. The Renaissance period brought crucial insights with Harvey's discovery of blood circulation. In the 20th century, the Framingham Heart Study provided a pivotal shift, formally defining HF as a clinical syndrome with diagnostic criteria. Over the decades, definitions of HF have evolved, integrating advancements in pathophysiology, biomarkers and imaging techniques. Initially focused on symptomatic and clinical presentations, modern definitions emphasise underlying structural and functional cardiac abnormalities. This evolution reflects the growing complexity and precision of diagnosing and managing HF. A historical perspective underscores the progressive refinement in HF definitions, which enhances diagnostic precision and therapeutic strategies, ultimately improving patient outcomes. Understanding this evolution is crucial for appreciating contemporary HF management and anticipating future advances.

Diuretic therapy is not associated with improved outcomes in heart failure and may cause significant side effects. Counteracting the core pathophysiological mechanisms of heart failure through neurohormonal blockade while reducing reliance on diuretics is potentially the most effective method of decongestion.

Aldosterone is a key regulator of fluid and electrolyte balance in the body. It is often dysregulated in heart failure (HF) and is a key driver of cardiac remodelling and worse clinical outcomes. Potassium regulation is essential for normal cardiac, gastrointestinal and neuromuscular function. Serum potassium fluctuations are largely determined by aldosterone, the final step of the renin-angiotensin-aldosterone system. Dyskalaemia (i.e. hypokalaemia and hyperkalaemia) is prevalent in HF because of the disease itself, its therapies and related comorbidities such as chronic kidney disease. Prognostic implications of abnormal serum potassium follow a U-shaped curve, where both hypokalaemia and hyperkalaemia are associated with adverse outcomes. Hypokalaemia is associated with increased mortality, starting from potassium <4.0 mmol/l but especially at potassium <3.5 mmol/l. Hyperkalaemia, along with increasing arrhythmia risk, limits the use of lifesaving renin-angiotensin- aldosterone system inhibitors, which may have long-term survival implications. The advent of novel potassium binders aims to manage chronic hyperkalaemia and may allow for uptitration and optimal dosing of guideline-recommended therapy. This review discusses the impacts of dyskalaemia in HF, along with management strategies, including the relevance of potassium binder use in optimising HF treatment. Current and potential future aldosterone-modulating therapies, such as non-steroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are also discussed.

Treatment for heart failure has experienced a major revolution in recent years, and current evidence shows that a combination of four medications (angiotensin receptor-neprilysin inhibitors + β-blockers + mineralocorticoid receptor antagonists + sodium.glucose cotransporter 2 inhibitors) offer the greatest benefit to our patients with significant reductions in cardiovascular mortality, heart failure hospitalisations and all-cause mortality. Unfortunately, despite their proven benefits, the implementation of these therapies is still low. Clinical inertia, and unfounded fear of using these drugs might contribute to this. Recently, evidence from randomised clinical trials has shown that intensive implementation of these therapies in patients with heart failure is safe and effective. In this review, we attempt to tackle some of these misconceptions/fears regarding medical therapy for heart failure and discuss the available evidence showing the best strategies for implementation of these therapies.

Acute myocarditis is an inflammatory disease of the heart that may occur in the setting of infection, immune system activation or exposure to certain drugs. Often, it is caused by viruses, whereby the clinical course is usually benign; however, it may also present with rapidly progressive fulminant myocarditis, which is associated with high morbidity and mortality. This review highlights the critical red flags - from the clinical, biochemical, imaging and histopathological perspectives - that should raise the index of suspicion of acute myocarditis. We also present an illustrative case of a young female patient with rapidly progressive cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation as a bridge to orthotopic heart transplantation. The patient showed no clinical or echocardiographic recovery signs and eventually underwent orthotopic heart transplantation. Furthermore, we elaborate on the classifications of acute myocarditis based on clinical presentation and histopathology classifications, focusing on identifying key red flags that will inform early diagnosis and appropriate management in such challenging cases.