Over 26 million people worldwide suffer from heart failure, a disease associated with a 1 year mortality rate of 22%. Half of these patients present heart failure with preserved ejection fraction (HFpEF), for which there is no available therapy to improve prognosis. HFpEF is strongly associated with aging, inflammation, and comorbid burden, which are thought to play causal roles in disease development. Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory actions and promote tissue healing, thus representing an attractive therapeutic option in HFpEF. In this review, we summarize recent data suggesting that a two-hit model of immune dysregulation lies at the heart of the HFpEF. A first hit is represented by genetic mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), which skew immune cells toward a pro-inflammatory phenotype, are associated with HFpEF development in animal models, and with immune dysregulation and risk of HF hospitalization in patients. A second hit is induced by cardiovascular risk factors, which cause subclinical cardiac dysfunction and production of danger signals. In mice, these attract proinflammatory macrophages, Th1 and Th17 cells into the myocardium, where they are required for the development of HFpEF. MSCs have been shown to reduce the pro-inflammatory activity of immune cell types involved in murine HFpEF in vitro, and to reduce myocardial fibrosis and improve diastolic function in vivo, thus they may efficiently target immune dysregulation in HFpEF and stop disease progression.

With recent guidelines expanding transcatheter aortic valve replacement (TAVR) to younger patients, indications for redo-TAVR will also likely increase. When compared with TAVR, redo-TAVR is a rare and novel procedure. Current clinical data derived from registries suggest excellent safety, with low rates of 30-day and 1-year mortality following redo-TAVR. Proper understanding of data from bench studies regarding optimal valve configurations, of patient anatomy and of the technical properties of transcatheter heart valves (THV) is essential for patient selection and procedural success. Lifetime management of redo-TAVR should start before the index procedure, as the choice of the index THV has a major impact on the feasibility of redo-TAVR. Procedural optimization by adequate valve sizing, commissural alignment and adequate implant depth of both index and redo-THV are critical determinants of optimal hemodynamics for maximized valve longevity, as well as lifelong coronary access.

Aims: Catheter ablation (CA) plays a central role in the management of electrical storm (ES). PAINESD and iVT are two validated scores commonly used to assess periprocedural risk in patients undergoing ventricular tachycardia (VT) ablation. This study aimed to evaluate the association between CA and mortality in ES patients stratified by PAINESD and iVT risk scores. Methods and results: We included 606 patients admitted for ES across four French centres. Risk was assessed using PAINESD and iVT scores. Mortality at 1 year was compared according to risk group and CA status. Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on predefined clinical variables. Forty-one per cent of patients were classified as high-risk using the PAINESD score, and 39.4% using the iVT score. Catheter ablation was performed in 42.4% of the cohort, including 39.4% of hi-PAINESD and 35.5% of hi-iVT patients. After adjustment, CA was associated with lower 1-year mortality in both high- and low-risk groups (adjusted HR: 0.42 [95% CI: 0.26–0.66], P = 0.0002 for hi-PAINESD; 0.31 [0.18–0.53], P < 0.0001 for hi-iVT). Inverse probability of treatment weighting-weighted models yielded consistent results. In exploratory interaction analyses, the iVT score—but not PAINESD—identified high-risk patients who may derive earlier survival benefit from VT ablation. Conclusion: In patients with electrical storm, VT ablation was associated with lower 1-year mortality across both low- and high-risk profiles. The iVT score may help identify high-risk patients who derive earlier benefit from ablation.