Asymptomatic hyperuricemia is defined by serum uric acid levels above 6.2 mg/dl in women and 7 mg/dl in men. In the presence of monosodium urate crystal formation and articular inflammation, hyperuricemia may become symptomatic (namely nephrolithiasis and gout). Uric acid results from purine catabolism and is at the centre of a complex metabolic interplay that involves oxidative stress, inflammation, renin–angiotensin–aldosterone system (RAAS) activation and insulin resistance. Uric acid levels present a continuous relation with conditions like hypertension and chronic kidney disease (CKD) and are reported to have an impact on risk of cardiovascular events. However, whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain and matter of further investigation. Treating symptomatic hyperuricemia involves lowering uric acid drugs and controlling inflammation. Urate-lowering agents are well tolerated but show minimal impact on cardiovascular events in patients with gout. Use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, whereas addressing cardiovascular issues with guideline-recommended therapies lowers uric acid and reduces the occurrence of cardiovascular events. Regular assessment of uric acid and clinical symptoms is advised before starting and renewing a urate-lowering treatment.

Chronic obstructive pulmonary disease (COPD) and heart failure (HF) frequently coexist and interact through complex and bidirectional hemodynamic mechanisms that amplify symptoms’ burden and complicate clinical management. The present review explores the impact of COPD across the HF spectrum, particularly in HF with preserved ejection fraction (HFpEF), where comorbidities, such as COPD, exert a dominant role in disease expression. COPD-induced hyperinflation reduces cardiac preload and increases right ventricular afterload, while HF-related congestion impairs pulmonary function and gas exchange, illustrating a tight cardiorespiratory coupling. Diagnostic challenges stem from overlapping symptoms and the limited specificity of biomarkers, such as natriuretic peptides, especially in HFpEF. Cardiopulmonary exercise testing (CPET) emerges as a valuable tool for distinguishing between cardiac and pulmonary limitations and guiding individualized treatment strategies. From a therapeutic standpoint, β 1-selective blockers are not only safe in COPD patients but are pivotal in those with HF with reduced ejection fraction (HFrEF), where they have been demonstrated to improve survival and reduce both HF and COPD exacerbations. Concerns regarding bronchodilator safety in HF remain largely theoretical, with current evidence supporting their continued use when clinically indicated. Ultimately, optimal care for patients with coexisting COPD and HF requires a phenotype-specific approach, incorporating insights from pathophysiology, diagnostic innovation, and evidence-based pharmacotherapy to improve outcomes in this challenging patient population.

Heart failure (HF) is a multifactorial and pathophysiological complex syndrome, involving not only neurohormonal activation but also oxidative stress, chronic low-grade inflammation, and metabolic derangements. Central to the cellular defence against oxidative damage is nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that orchestrates antioxidant and cytoprotective responses. Preclinical in vitro and in vivo studies reveal that Nrf2 signalling is consistently impaired in HF, contributing to the progression of myocardial dysfunction. The loss of Nrf2 activity intersects a complex network of pathological processes involving neurohormonal activation, ischaemia–reperfusion injury, and sustained inflammation, exacerbating cardiac functional decline. Nrf2 deficiency diminishes resilience to clinical conditions such as hypertension, diabetic cardiomyopathy, and cancer therapy-related cardiotoxicity, favouring the transition from initial cardiac dysfunction to overt HF. Initial evidence supports the therapeutic potential of Nrf2 modulation. Lifestyle interventions such as exercise training, various natural compounds, and established cardiovascular agents (e.g. sodium-glucose cotransporter-2 inhibitors) have been shown to restore Nrf2 activity. This review analyses the emerging role of Nrf2 as both a key player in HF pathogenesis and a promising therapeutic target, highlighting available evidence across HF phenotypes and addressing the controversies surrounding its pharmacological modulation.

Background: The RoMa classification, based on peak heart rate and oxygen pulse derived from cardiopulmonary exercise testing, was recently proposed to stratify patients with hypertrophic cardiomyopathy by physiological reserve during exercise. We aimed to externally validate RoMa in an independent multicenter cohort with hypertrophic cardiomyopathy and assess its association with long‐term clinical outcomes. Methods: In this retrospective multicenter cohort study patients with hypertrophic cardiomyopathy, undergoing cardiopulmonary exercise testing, were consecutively enrolled. Patients were enrolled regardless of left ventricular outflow tract obstruction and were naïve to disease‐specific therapy (eg, mavacamten). Patients were categorized into RoMa I to IV based on percentage of predicted heart rate and oxygen pulse. The primary end point was a composite of all‐cause and cardiovascular death, sudden cardiac death, or aborted sudden cardiac death, heart failure–related hospitalization, stroke, systemic embolism, surgical myectomy, and heart transplantation. Results: The study included 292 patients (age 51 [36–63] years, 70% male sex, 30% with obstructive left ventricular outflow tract). Functional capacity declined hierarchically across RoMa groups (peak oxygen uptake 29.2 to 17.9 mL/kg/min; P ‐trend <0.001). During follow‐up (≈6 years), 68 composite events occurred. Kaplan–Meier analysis showed significant differences in event‐free survival across groups (log‐rank P =0.019). In multivariable analysis, RoMa II to IV compared with RoMa I were independently associated with higher hazard ratios (HRs) for the composite outcome (HRs, 3.89–5.37; all P <0.05), whereas genotype, LVEF <50%, male sex, and left ventricular outflow tract obstruction were not predictive. Conclusions: The RoMa classification independently predicts long‐term, clinically relevant outcomes in hypertrophic cardiomyopathy regardless of left ventricular outflow tract obstruction and may provide a novel approach to risk stratification.