Stefano Taddei

Resistant hypertension (RHTN) is estimated to affect approximately 15% of all patients with hypertension, although its reported prevalence varies according to the blood pressure (BP) thresholds used for diagnosis, the criteria applied to exclude secondary or pseudoresistant hypertension, and the characteristics of the study populations. Regardless of its current prevalence, RHTN is expected to be encountered with increasing frequency in routine clinical practice, driven by the rising prevalence of conditions that are directly or indirectly linked with its increased risk, such as obesity, diabetes mellitus, and chronic kidney disease (CKD). Consequently, recent clinical trials and hypertension guidelines have devoted substantial attention to RHTN, also considering its association with an increased risk of cardiovascular events and renal failure. In this narrative review, we summarize mechanistic insights and evidence from randomized clinical trials and real-world studies, as well as recommendations from current international guidelines, to provide an updated perspective on the management of RHTN. Among multiple systems, activation of the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system represents a central pathophysiological mechanism in RHTN, promoting sodium retention and vascular dysfunction. β-blockers counteract SNS overactivity, a target mechanism not addressed by other first-line therapies, and have compelling indications in most comorbidities associated with RHTN, including coronary artery disease, heart failure, and atrial fibrillation. They can be used across diverse patient populations, including those with advanced CKD, and their side effects can be readily monitored and managed. Evidence from randomized trials and real-world studies supports their efficacy, tolerability, and safety even in high-risk populations. Emerging strategies, including a quadruple single-pill combination containing a β-blocker, may enhance adherence, optimize BP control, and simplify RHTN management.

BACKGROUND: Moderate and severe tricuspid regurgitation (TR) is associated with poor outcomes, yet current grading systems do not fully capture circulatory heterogeneity. We investigate the relationship of cardiac index (CI) with rest-exercise hemodynamics, metabolic and inflammatory profiles, and clinical outcomes in moderate and severe TR. METHODS: We prospectively enrolled 300 outpatients with atrial secondary, nonatrial secondary, and lead-associated moderate and severe TRs without ≥moderate left-sided valve disease. All underwent comprehensive laboratory profiling and ultrasound evaluation at rest and during cardiopulmonary exercise. Patients were stratified by CI tertiles and followed clinically (primary end point: all-cause mortality or heart failure hospitalization). RESULTS: CI decreased with TR severity but showed wide interindividual variability. In patients with low CI, severe forward flow limitation was associated with more advanced right ventricle-pulmonary arterial uncoupling and biatrial dysfunction ( P P P <0.05 for all). CONCLUSIONS: In moderate and severe TRs, CI profiling captures cardiac and extracardiac determinants of flow and independently predicts outcomes beyond conventional TR grading and staging. Both low and high CIs identify high-risk patients, while an intermediate CI indicates a balanced, prognostically favorable state. CI profiling may refine risk stratification, guide individualized treatment strategies, and optimize patient selection and timing for tricuspid valve interventions.

Background and Aims: True resistant hypertension leads to higher rates of target-organ damage, cardiovascular morbidity, and mortality compared with general hypertension. Guidelines recommend adding a fourth drug to triple therapy if blood pressure (BP) remains uncontrolled. This Phase 3 trial aimed to demonstrate superior BP reduction with the first full-dose quadruple single-pill combination (SPC) vs triple antihypertensive therapy for uncontrolled BP. Methods: QUADRO was a multicentre, Phase 3, randomized, controlled, double-blind trial in resistant hypertension. After an 8-week run-in period on perindopril/indapamide/amlodipine, participants were randomized 1:1 to quadruple SPC perindopril/indapamide/amlodipine/bisoprolol or continued the same triple therapy for 8 weeks. Efficacy assessments included office systolic BP (SBP) at Week 8 (primary outcome) and 24 h ambulatory BP monitoring (ABPM). The primary analysis examined all randomized patients with uncontrolled SBP; safety analyses included all patients who received at least one dose of study medication. This trial is registered under EudraCT No. 2020-004891-16. Results: Overall, 183 patients (quadruple SPC, n = 89; triple therapy, n = 94) were randomized. After 8 weeks, decreases in office SBP [−8 mmHg; 95% confidence interval (CI): −11.99, −4.09; P < .0001] and 24 h-ABPM (−8 mmHg; 95% CI: −10.95, −4.11; P < .0001) were greater with quadruple SPC vs triple therapy. Both treatments were well tolerated; 10 participants (11%) receiving quadruple SPC and 8 (8%) receiving triple therapy had at least one treatment-emergent adverse event (TEAE), and no serious or severe TEAEs were reported. Conclusions: The first full-dose quadruple antihypertensive SPC (perindopril/indapamide/amlodipine/bisoprolol) demonstrated superiority over perindopril/indapamide/amlodipine, offering an effective alternative therapy for confirmed resistant hypertension.

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks.

Cardiopulmonary exercise testing combined with exercise stress Echocardiography (CPET-ESE) is an advanced diagnostic modality for evaluating cardiovascular disease and tailoring patient-specific treatment strategies. By integrating metabolic, ventilatory, and hemodynamic data with real-time imaging, CPET-ESE offers a comprehensive assessment of cardiovascular function under physiological stress. CPET provides detailed insights into metabolic and ventilatory performance, while ESE allows for the dynamic visualisation of cardiac structure and function during exercise. This review outlines the physiological foundations and core parameters of CPET and ESE, emphasising their complementary roles in cardiovascular diagnostics and prognostication and exploring their clinical value for evaluating unexplained dyspnoea and exercise-induced hemodynamic abnormalities. CPET-ESE plays a pivotal role in detecting subtle hemodynamic abnormalities, assessing functional capacity, and contributing to earlier diagnosis, targeted interventions, and improved clinical outcomes.

The clinical use of β-adrenergic receptor antagonists (β-blockers) began nearly 60 years ago with the invention of propranolol by Black et al.1 The initial therapeutic use was for angina pectoris, ...

Nicola Riccardo Pugliese, Stefano Taddei; Low-dose aspirin therapy for primary prevention of cardiovascular disease: where are we at?, European Journal of Preve