Centenarians — individuals aged ≥100 years — provide a unique human model for understanding resilience to cardiovascular ageing. Although cardiovascular and metabolic diseases, including hypertension, heart failure, atrial fibrillation and chronic kidney disease, are common in centenarians, their onset is typically delayed relative to that in individuals aged 80–100 years. Centenarians characteristically have structural changes in the heart and vessels, including concentric left ventricular remodelling, increased myocardial stiffness and vascular ageing, but often without the expected burden of myocardial infarction or overt heart failure. Their cardiometabolic profile is generally favourable, marked by preserved insulin sensitivity in cohorts with a low prevalence of diabetes mellitus, mid-range lipid levels and a low prevalence of obesity. Centenarians also have a distinctive inflammatory and gastrointestinal phenotype, characterized by chronic low-grade inflammation with elevated anti-inflammatory signalling, a gut microbiome that more closely resembles that of younger adults, and preserved intestinal barrier integrity. Genetically and epigenetically, exceptional longevity reflects highly polygenic contributions, selective maintenance of genomic stability and markedly younger epigenetic age compared with chronological age. In this Review, we summarize data on the cardiovascular system among centenarians by framing observations of longevity as a composite of delayed pathology, adaptive compensation and survivorship selection. Understanding the biological, behavioural and environmental mechanisms underlying cardiovascular resilience in extreme longevity might inform strategies to extend cardiovascular healthspan across all ages. In this Review, Lucia and colleagues describe the cardiometabolic, structural, genetic and inflammatory profiles of centenarians that distinguish them from their shorter-lived peers, highlighting the biological, behavioural and environmental factors driving cardiovascular resilience in extreme longevity.
Cardiac pacing has undergone a fundamental paradigm shift from conventional right ventricular apical pacing towards physiological activation of the native conduction system of the heart. Decades of evidence have established that chronic right ventricular pacing induces ventricular dyssynchrony, contributing to pacing-induced cardiomyopathy and adverse clinical outcomes. Conduction system pacing, which engages the intrinsic His–Purkinje network of the heart, has emerged as a transformative approach that preserves or restores the natural ventricular activation sequence. His bundle pacing, the earliest form of conduction system pacing, provided proof of concept but is limited by technical challenges and high capture thresholds. Left bundle branch area pacing has since become the dominant modality, offering greater procedural success, lead stability and broader applicability: from management of bradycardia and prevention of pacing-induced cardiomyopathy to cardiac resynchronization therapy in heart failure. Bachmann bundle area pacing is an emerging atrial counterpart: by capturing a preferential interatrial conduction pathway, this approach reduces interatrial conduction delay and produces a more physiological atrial activation sequence than conventional right atrial appendage pacing. Bachmann bundle area pacing might, therefore, help to prevent atrial fibrillation. In this Review, we bring these ventricular and atrial strategies together under the unifying principle of physiological pacing, describe their mechanistic basis and technical evolution, appraise the latest evidence from randomized trials and address the practical questions that arise in clinical application, indicating where more evidence is required. Conduction system pacing has transformed cardiac pacing by engaging the intrinsic His–Purkinje network, thereby preserving or restoring the natural ventricular activation sequence and avoiding pacing-induced cardiomyopathy. In this Review, Choi and colleagues discuss the various forms of ventricular and atrial physiological pacing, their mechanistic basis and technical evolution, and the latest trial evidence for clinical applications.
The POET II trial reports that stopping antibiotic treatment in patients with endocarditis once they are clinically stable shortens the treatment duration without excess risk of death or surgery, but triples the rates of relapse of endocarditis or bacteraemia. This response-guided strategy marks a genuine shift beyond the oral-antibiotic-switch paradigm from the POET trial, and the safety of the approach will depend on rigorous patient selection and close multidisciplinary follow-up.
