This review summarizes contemporary evidence on transcatheter aortic valve replacement (TAVR) explantation, emphasizing epidemiology, indications, operative challenges, outcomes, risk prediction, and implications for lifetime valve management. As TAVR expands to younger and lower-risk patients, explantation is becoming an increasingly relevant component of lifetime valve care. Recent systematic reviews, registries, national databases, and center experiences show that TAVR explant is technically complex, frequently requires concomitant procedures, and carries early mortality that exceeds conventional risk predictions. TAVR-in-TAVR is feasible in selected patients with structural valve degeneration but may be limited by infection, small annulus, coronary obstruction risk, or impaired future coronary access. TAVR explant should be considered during index valve selection. Heart Team planning should incorporate durability, coronary access, annular size, redo-TAVR feasibility, and surgical explant complexity, particularly in younger patients.
This review examines the 2025 American Heart Association/American College of Cardiology multisociety hypertension guideline, placing its recommendations in historical context and evaluating the supporting evidence across major clinical populations. The 2025 guideline retains the 2017 blood pressure categories and treatment goal of less than 130/80 mmHg but introduces the race-free PREVENT equations, uses a 7.5
Although imaging remains central to diagnosis and risk stratification, circulating biomarkers provide complementary information reflecting myocardial stress, fibrosis, extracellular matrix remodeling, inflammation, and metabolic dysregulation. The purpose of this review is to critically evaluate current and emerging circulating biomarkers in MVP and to assess whether these biomarkers may improve individualized management of this disease. Natriuretic peptides are the most validated biomarkers in MVP, consistently predicting adverse outcomes and providing complementary prognostic information that may help inform the timing of surgical intervention, particularly in asymptomatic patients with significant mitral regurgitation. In contrast, evidence supporting fibrosis and inflammation mediators, proteomics, metabolomics, and circulating microRNAs remains emerging. In arrhythmic MVP, no circulating biomarker is currently recommended for routine risk stratification. Future research should prioritize phenotype-specific MVP registries, biomarker–CMR integration, multi-omics profiling, and biomarker-guided interventional trials.
Circulating biomarkers are increasingly utilized in cardio-oncology for risk stratification, early detection, and prognostication of cancer therapy-related cardiovascular toxicity. This review summarizes the current evidence supporting established and emerging biomarkers, with a focus on their clinical utility and limitations. Cardiac troponins and natriuretic peptides remain the most widely studied biomarkers, with troponins demonstrating consistently strong prognostic value and natriuretic peptides showing more variable predictive performance for cardiotoxicity. Emerging data highlight limitations in biomarker-guided therapeutic strategies, with inconsistent evidence for improved clinical outcomes. Novel biomarkers, including soluble suppression of tumorigenicity 2 (sST2), galectin-3, myeloperoxidase (MPO), inflammatory markers, and circulating microRNAs, show early promise for detecting subclinical injury through distinct pathophysiological pathways but lack standardization and validation for routine clinical use. Imaging biomarkers, including global longitudinal strain (GLS) and cardiac MRI parametric mapping, complement circulating markers and are increasingly integrated into surveillance strategies, with emerging randomized evidence supporting GLS-guided cardio-protection. Increasing emphasis has been placed on multimarker approaches and their integration with imaging and clinical context to improve diagnostic accuracy, although prospective validation of these strategies remains needed. Circulating biomarkers play an increasingly important role in contemporary cardio-oncology practice; however, no single biomarker is sufficient to guide management across all clinical scenarios. A multimodal strategy incorporating biomarkers, imaging, and clinical assessment is increasingly recommended. Future research should focus on standardization, validation of emerging biomarkers, and defining the role of biomarker-guided interventions to improve cardiovascular and cancer outcomes.
The subcutaneous ICD (S-ICD) and the extravascular ICD (EV-ICD) both avoid intravascular hardware, but they solve sensing and detection differently. This review compares their sensing architectures, detection and discrimination algorithms, therapy capabilities, and system-specific complications, along with practical considerations including extraction, MRI compatibility, and patient-reported outcomes. Inappropriate shock rates have declined substantially for both platforms through algorithmic refinements, two-zone programming and SMART Pass for S-ICD, and improved implant technique with a P-wave oversensing discriminator for EV-ICD. Oversensing patterns differ: T-wave oversensing predominates in S-ICD, while P-wave oversensing is the primary concern in EV-ICD. Lead fracture, though rare, has distinct mechanisms in each system. Quality-of-life data suggest higher device acceptance and fewer body-image concerns with EV-ICD, while S-ICD demonstrates comparable psychosocial outcomes to transvenous systems with potential advantages in anxiety reduction. Optimal non-transvenous ICD performance requires matching the platform's sensing and discrimination characteristics to the individual patient's arrhythmia substrate and clinical profile. Continued algorithmic development and refined implant techniques are expected to further reduce inappropriate therapy rates for both systems, while growing extraction experience and favorable quality-of-life data support expanding adoption.
After years of declining use of thallous chloride-201 (thallium) for myocardial perfusion imaging (MPI), commercial production in the U.S ceased in 2022. Recognizing unique patient-care roles that thallium can serve, it was reintroduced in July 2026. A new generation of cardiologists has no or little familiarity with this radiopharmaceutical, and even many experienced nuclear cardiology practitioners are unfamiliar with its role to improve accuracy of cardiac amyloid radionuclide imaging with bone-avid tracers, gaps which this review aims to address. Claims data indicate that while thallium use progressively declined, during the last few years of its availability this appears to have plateaued, with approximately 5
We examined the landscape of publicly available cardiac imaging datasets to assess how their distribution and construction shape bias and equity in cardiovascular AI. Across 38 publicly available echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography datasets, nearly 80
To provide a review of current transcatheter interventions in women with congenital heart disease, with a focus on sex-specific considerations in diagnosis, management, and follow-up. As the field of pediatric cardiology advances and patients with previously life-limiting diagnoses now survive well into adulthood, there is a growing need to pursue management strategies that improve quality of life. Unfortunately, in the treatment of cardiovascular disease, women have historically been underrepresented in research studies and clinical trials, which may limit the generalizability of available evidence and contribute to disparities in outcomes. Women with congenital heart disease (CHD) are an even more vulnerable population given the relatively low prevalence of CHD. This review discusses several CHD lesions and current trends in diagnosis, management, and follow-up in women. Additionally, it highlights sex-specific considerations in this unique patient population. Future initiatives and applications that may help improve the lifetime care of women with CHD are also reviewed. Although there have been increasing efforts to improve the inclusion of women in medical research in recent years, substantial gaps in representation remain. As emerging technologies are increasingly introduced in the CHD field, there is an important opportunity to improve the representation of women in studies evaluating procedural outcomes. Tools such as artificial intelligence and machine learning may help facilitate scalable screening and risk-stratification strategies for women with CHD.
To review evidence on the role of circulating biomarkers associated with lower extremity peripheral artery disease (PAD) and adverse outcomes in people with PAD. The ankle-brachial index (ABI) is a non-invasive, guideline-recommended test to diagnose PAD. Circulating biomarkers may offer additional insight into early detection of PAD and risk stratification of adverse events in people with PAD. Observational studies show that higher levels of inflammatory biomarkers (such as C-reactive protein, interleukin-6, soluble intracellular adhesion molecule-1), thrombosis biomarkers (such as D-dimer, fibrinogen), cardiac biomarkers (such as troponin, N-terminal pro-brain natriuretic peptide, lipoprotein A), and omic markers are associated with increased risk of developing PAD. Some of these markers are also associated with severity and adverse outcomes in people with PAD. While association studies have shown links between circulating biomarkers and PAD, no single biomarker or combination of markers is currently guideline-recommended for routine clinical use in diagnosis or management of PAD due to absence of clinical trial data showing that circulating biomarkers definitively improve outcomes in PAD. The current state of biomarkers in PAD suggests that further study is needed to determine whether biomarker-guided therapy will improve diagnosis or clinical outcomes for people at risk and people with PAD.
To evaluate the reasons underlying the translational failure of cardioprotection in reperfused ST-elevation myocardial infarction (STEMI) and propose a framework for designing future clinical cardioprotection trials. The 2024 JACC Scientific Statement on reperfusion injury reframed the field as a network of interrelated injury pathways but stopped short of providing a clinically actionable framework. Contemporary cardioprotection trials in enriched patient STEMI cohorts have produced largely neutral results: STEMI-DTU, PiCSO-AMI-I, EURO-ICE, and COOL AMI EU failed to demonstrate cardioprotection on cardiovascular magnetic resonance (CMR) infarct size. Although the PITRI trial showed reduced periprocedural platelet reactivity with cangrelor there was no reduction in infarct size or microvascular obstruction (MVO), exemplifying proximal target engagement without affecting imaging surrogates. In contrast, the supersaturated oxygen (SSO₂) programme arc – AMIHOT → AMIHOT-II → IC-HOT → IC-HOT-MICRO – showed progressive patient enrichment yielding a progressive mechanistic signal, particularly in patients with severe coronary microvascular dysfunction. The Collaborative Registry on CMR in STEMI confirmed MVO ≥ 2.6
To summarize the current understanding of the relationships between endogenous and exogenous androgens and cardiovascular disease in postmenopausal women. Endogenous testosterone and dehydroepiandrosterone exhibit a J-shaped relationship with cardiovascular mortality. The association of exogenous testosterone with adverse cardiovascular outcomes is highly dependent on dose and route of administration. Non-oral testosterone administration is associated with neutral risks, but close monitoring of total testosterone levels is obligatory. Estrogen, progesterone, and androgens levels shift during menopause transition, and the ratios between levels have a greater impact on cardiometabolic and cardiovascular outcomes than absolute levels. While exogenous testosterone modestly improves hypoactive sexual desire, it is unknown if restoring testosterone levels to premenopausal physiologic conditions can also mitigate other age-related physical changes. Future studies addressing the timing, dose, route of administration, treatment duration, and combination therapy with estrogen in postmenopausal women of all racial and ethnicities are needed.
Lipoprotein(a) [Lp(a)] remains a well-established, genetically determined predictor of cardiovascular risk due to its pro-atherogenic and pro-thrombotic effects. This review examines the paradoxical relationship between Lp(a) and metabolic dysfunction-associated steatotic liver disease (MASLD), where Lp(a) levels decline with advanced fibrosis despite persistently elevated cardiovascular disease (CVD) risk. Studies consistently show an inverse association between Lp(a) and MASLD severity. Evidence suggests that lower Lp(a) levels are a consequence of hepatic dysfunction rather than protective against cardiovascular disease. Additionally, selective hepatic insulin resistance increases VLDL production, diverting apoB100 from Lp(a) assembly, while insulin directly suppresses apolipoprotein(a) synthesis. Genetic variants linked to MASLD may further impair hepatic lipid secretion and reduce Lp(a). Lower Lp(a) levels in MASLD likely reflect impaired hepatic synthetic function rather than reduced cardiovascular risk. Recognizing this paradox may improve risk stratification and interpretation of Lp(a) in patients with MASLD
This review examines cardiovascular complications of multiple myeloma and anti-myeloma therapy, emphasising integrated systems-based cardiovascular management and the institutional model developed at the University College London Hospital Cardio-Oncology (CO) Centre of Excellence. Cardiovascular vulnerability in multiple myeloma reflects baseline risk, disease-related factors, including cardiac amyloidosis, and treatment-related cardiotoxicity. A longitudinal approach should begin before therapy with multidimensional risk stratification incorporating patient, disease, and treatment factors, with intermediate- and high-risk patients referred for CO review. During treatment, active surveillance using clinical assessment, cardiac biomarkers and imaging, with vigilance for cardiac amyloidosis, enables rapid CO referral and timely intervention. Survivorship care should include annual cardiovascular review, risk-factor optimisation, and monitoring for late toxicity. Existing evidence and real-world experience support integrated CO services combining rapid-access clinics, high-volume cardiac imaging, timely decision-making, inpatient consultation, multidisciplinary collaboration, and survivorship surveillance while preserving cardiovascular health and access to effective anti-myeloma therapy.
Intraprocedural anticoagulation during percutaneous coronary intervention (PCI) remains particularly challenging in high-risk and underrepresented populations, where the balance between thrombotic and bleeding risk is complex and often unpredictable. This review summarizes contemporary evidence and remaining knowledge gaps regarding anticoagulant selection, dosing, and monitoring in patients with advanced chronic kidney disease (CKD) or end-stage renal disease, cirrhosis, nonagenarians, thrombocytopenia, chronic oral anticoagulation, mechanical circulatory support, and STEMI following fibrinolytic therapy. These populations are frequently excluded from randomized clinical trials. In patients with STEMI following fibrinolytic therapy, optimal anticoagulation strategies remain uncertain, with evidence suggesting potential benefit of anticoagulant continuity. Mechanical circulatory support devices introduce additional complexity due to device-related thrombosis and bleeding risks, requiring dynamic, device-specific anticoagulation and monitoring strategies. Special populations such as elderly patients, cirrhosis, and CKD present unique pathophysiologic challenges, including altered pharmacokinetics and rebalanced hemostasis. Similarly, patients on chronic oral anticoagulation require individualized periprocedural strategies, as baseline therapy alone may be insufficient and supplemental intraprocedural anticoagulation is often necessary. Conventional bleeding risk scores demonstrate reduced predictive performance in these populations, highlighting important limitations in current risk stratification. Emerging evidence supports a shift toward precision-guided anticoagulation strategies that integrate actionable patient-specific factors, including renal function, platelet count, liver disease severity, and procedural complexity, along with pharmacogenomics and real-time monitoring. Advances in machine learning–based risk prediction and artificial intelligence-driven clinical decision support tools further offer the potential to enhance individualized care. However, most available evidence remains extrapolated from broader populations, and dedicated prospective studies are needed to define optimal anticoagulant selection, dosing, and monitoring strategies in these high-risk groups.
Postnatal shutdown of the mammalian cardiomyocyte cell cycle underpins limited regenerative capacity of the adult heart. An epigenetic programme regulates a switch at birth from a proliferative state to functional maturity. Identification of the molecular components regulating this switch has revealed therapeutic opportunities for heart regeneration that have started entering the clinic. Genome-wide analyses reveal that histone modifications and DNA methylation remodel chromatin in adult cardiomyocytes, downregulating cell cycle activation genes while upregulating maturation genes. Epigenetic regulation of upstream transcriptional pathways (e.g. YAP, WNT and Notch) prevents cell cycle activation in the adult heart. Upregulating glycolysis or suppressing oxidative metabolism enhances cardiac repair following injury, with hypoxia demonstrating safety in humans. Gene therapy techniques enabling myocardial targeting have enhanced the translation of cardiac regenerative therapies, with YAP upregulation paving the way for future trials. The cardiomyocyte cell cycle is regulated by CDKs/cyclins controlled by transcriptional networks that are epigenetically suppressed in the postnatal period. Adult cardiomyocytes also harbour structural barriers and a metabolic state preventing proliferation. Pharmacological and genetic manipulation of these mechanisms can re-activate adult cardiomyocyte proliferation. However, regenerative therapies are challenged by the intrinsic link between proliferation and epigenetics, metabolism, and ultimately cardiac function.
To provide an overview of diagnostic tests for Stage B heart failure (SBHF), synthesizing evidence from guidelines and clinical studies. Advances in diagnostic technologies have expanded the ability to identify subclinical myocardial remodelling and early myocardial injury before symptom onset. We highlight the central role of transthoracic echocardiography as the cornerstone diagnostic modality for detecting subclinical myocardial remodelling and dysfunction, including the use of speckle tracking echocardiography. In parallel, circulating biomarkers, especially natriuretic peptides and high-sensitivity cardiac troponins, can play important roles in the detection and risk stratification of SBHF. Additional diagnostic approaches, including electrocardiography, chest X-ray, cardiac magnetic resonance imaging, cardiac computed tomography, nuclear imaging, and exercise stress testing, are reviewed for their adjunctive roles in selected clinical contexts. Emerging applications of artificial intelligence are explored as promising strategies to increase the diagnostic precision, scalability, and early detection of SBHF in clinical practice. SBHF – representing a subclinical phase of HF characterized by structural cardiac abnormalities, functional impairment, or persistently abnormal cardiac biomarkers in individuals – has historically been difficult to recognize in the community. Advances in imaging, biomarkers, and AI may improve the feasibility of detecting this entity, creating a crucial window for intervention, because timely risk stratification and preventive strategies during SBHF may attenuate progression to symptomatic HF and reduce its long-term clinical and economic burden.
Myocarditis is a heterogeneous inflammatory syndrome with aetiologies ranging from viral infection and drug hypersensitivity to systemic autoimmune/autoinflammatory disease and immune checkpoint inhibitor (ICI) therapy. In response to these triggers, the innate immune response and inflammasome activation can amplify myocardial injury via IL-1, providing a mechanistic rationale for IL-1 pathway inhibition as a targeted therapeutic strategy. This review synthesizes preclinical and clinical evidence for IL-1 blockade in myocarditis and related inflammatory cardiac syndromes. The immune system plays a central role in the pathogenesis of myocarditis, both in idiopathic/viral cases and in systemic autoimmune and autoinflammatory diseases (SAAD). Interleukin-1 (IL-1) has emerged as a key mediator linking inflammation to myocardial dysfunction, supported by experimental and translational evidence implicating activation of the NLRP3 inflammasome. Clinically, the randomized trial of anakinra in acute myocarditis (ARAMIS) did not improve outcomes in a largely low-risk cohort, but accumulating case reports and small series suggest potential benefit in fulminant/hyperinflammatory myocarditis and chronic active refractory myocarditis. In contrast, IL‑1 inhibitors have robust randomized and real-world evidence in recurrent pericarditis, supporting a myo‑pericardial inflammatory continuum and validating IL‑1 pathway engagement as an actionable target in selected inflammatory cardiac phenotypes. Together, these findings support the evolving concept of cardioimmunology. Current management of myocarditis remains largely supportive, with limited disease-modifying options. Anti-IL-1 therapies, particularly anakinra, have shown promising efficacy in selected severe and refractory cases, with a favourable safety profile. However, evidence is mainly derived from case reports and small series, and robust randomized data are lacking. Key clinical questions remain unresolved, including patient selection, timing of initiation, and treatment duration. Future studies should focus on identifying inflammatory endotypes and evaluating targeted immunomodulatory strategies, including in emerging settings such as ICI-associated myocarditis in which IL‑1 blockade remains investigational.
Heart failure remains a major cause of morbidity and mortality that is associated with myocardial changes in metabolism, contractile function, and molecular remodeling. Cardiomyopathies comprise a diverse group of disorders that can be triggered by various external and internal stressors. This review aims to cover the underlying molecular mechanism driving heart failure progression, at the level of alternative splicing. Alternative splicing is a fundamental mechanism that expands transcriptomic diversity through the differential inclusion or exclusion of exons. This process enables a single gene to generate multiple mRNA isoforms, thereby fine-tuning gene function in a context-dependent manner. Splicing outcomes are determined by a highly coordinated regulatory network, including cis-acting splicing elements, transcriptional kinetics, and trans-regulatory RNA-binding proteins, which together form a dynamic “splicing code” that responds to physiological and pathological stresses. In the heart, alternative splicing regulates cardiac cell homeostasis and normal physiological function. Dysregulated alternative splicing has been increasingly recognized as a key contributor to cardiovascular diseases, particularly in the context of sarcomere gene isoform switching. However, emerging evidence suggests that cardiomyopathies arising from distinct etiologies including dilated, ischemic, and cardiometabolic disorder are associated with unique splicing programs. Here, we provide a comprehensive overview of the regulatory mechanisms governing alternative splicing in the heart, with a particular emphasis on disease-specific splicing events across different forms of cardiomyopathy. We further discuss recent advances in targeting aberrant splicing for therapies as well as novel splicing analysis platforms, highlighting the potential of RNA-based strategies to modulate splicing in heart failure.
Atrial fibrillation (AF) and/or the need for oral anticoagulation (OAC) frequently coexist with stable chronic coronary syndrome (CCS). In this population, clinicians must carefully balance ischemic protection against bleeding risk. This review aims to synthesize available evidence and address whether antiplatelet therapy (APT) should be maintained on top of OAC in this specific subset. Recent trials have provided key evidence. AFIRE, EPIC-CAD, AQUATIC and ADAPT-AF-DES have all demonstrated that OAC monotherapy is not only non-inferior but also superior to combination therapy (OAC plus APT) in terms of net clinical benefit, with fewer major bleeding events and no increase in ischemic complications. The AQUATIC and AFIRE trials even showed an excess in mortality with prolonged combination therapy. Current evidence supports OAC alone as the preferred long-term antithrombotic strategy in patients with AF and stable CCS.
