Clonal hematopoiesis of indeterminate potential (CHIP) and the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are both linked to NLRP3-mediated cardiovascular inflammation, but their interaction has not previously been explored. This work proposes the CHIDT axis (clonal hematopoiesis–dysbiosis–TMAO), a feed-forward mechanism in which TET2 loss-of-function CHIP- and TMAO-generating Gram-negative gut dysbiosis mutually enhance cardiovascular risk. The model proceeds in three nodes. CHIP-associated intestinal immune dysregulation promotes luminal expansion of Gammaproteobacteria, which produce both trimethylamine via CntA/CntB-mediated L-carnitine oxidation and ADP-heptose as an obligate LPS biosynthetic intermediate. TMAO amplifies NLRP3 inflammasome activation through the SIRT3 → SOD2 → mtROS pathway. The evidence base of the CHIDT model is strongest for TET2-CHIP; the proposed extension to DNMT3A-CHIP rests on indirect, associative data and requires dedicated experimental confirmation before it can be considered established. TXNIP cascade, with predicted disproportionate potency in macrophages epigenetically primed by TET2 haploinsufficiency. High concentrations of TMAO have also been shown to suppress TET2 expression in endothelial cells through CYTB promoter hypermethylation, inducing NLRP3–GSDMD-dependent pyroptosis, although it remains unclear whether physiological TMAO levels can trigger this effect. Concurrently, ADP-heptose activates the ALPK1–TIFA–NF-κB pathway in bone marrow progenitors, favoring the expansion of mutant hematopoietic stem and progenitor cells. The model identifies three potential therapeutic strategies: NLRP3 inhibition, microbial TMA lyase inhibition, and microbiome-targeted reduction in Gram-negative bacteria. None has been tested in CHIP carriers stratified by plasma TMAO. Further studies in preclinical models and human cohorts integrating CHIP genotyping and TMAO quantification are needed to validate the CHIDT axis as a target for precision cardiovascular prevention.

Objectives: This study aimed to define the learning curve required for cardiac surgery residents to acquire basic technical and interpretive skills in transit-time flow measurement (TTFM) and high-resolution epicardial ultrasonography (HRUS) during coronary artery bypass grafting (CABG). Methods: Prospective, observational, single-center study evaluating performance using a novel scoring system combining functional (TTFM) and anatomical (HRUS) assessment criteria. This study was registered on ClinicalTrials.gov (Identifier: NCT06589323). Nine cardiac surgery residents without prior hands-on experience in TTFM or HRUS were enrolled. Twenty-seven elective CABG patients (67 grafts) were analyzed. Each measurement was compared with those obtained by an expert benchmark surgeon (N.T.) under standardized hemodynamic conditions. Results: Residents achieved the predefined primary endpoint (combined TTFM + HRUS score/number of grafts ≥ 11) after a median of 3 cases (IQR 2–4) and 7 anastomoses (IQR 7–10). Kaplan–Meier analysis showed a progressive increase in the probability of success, with a sharp rise after the seventh anastomosis. A shorter interval between attempts (<30 days) was significantly associated with earlier achievement of the endpoint (p < 0.05). Median acquisition time for TTFM was 25 s, with 90% of cases, though slightly lower success rates were observed for lateral and inferior wall targets. No resident- or procedure-related variable was independently associated with performance improvement. Conclusions: Mastery of basic TTFM and HRUS skills requires only a few cases and anastomoses, demonstrating a short and attainable learning curve. These findings challenge the perception of a steep learning process and support the routine use of intraoperative graft verification techniques in all CABG procedures.

Minimally invasive mitral valve repair: for every patient, for every surgeon or still a work in progress?

Objectives: Functional tricuspid regurgitation (TR) recurrence after concomitant mitral–tricuspid surgery remains associated with adverse long-term outcomes, while reintervention on the isolated tricuspid valve carries substantial operative risk. Despite increasing awareness of the prognostic importance of functional TR, concomitant tricuspid valve repair remains inconsistently adopted in contemporary practice, particularly in technically demanding procedures. We sought to identify predictors of recurrent TR and develop an individualized prediction model to support patient-tailored surgical planning. Methods: This single-center ambispective study included 178 consecutive patients undergoing concomitant mitral–tricuspid surgery between January 2012 and June 2019. Baseline clinical, echocardiographic and operative variables were retrospectively collected, whereas long-term clinical and echocardiographic follow-up was prospectively completed after Ethics Committee approval. Clinical, echocardiographic and operative variables were first evaluated by univariable Cox proportional hazards analysis. Based on their univariable association with recurrent TR, biological plausibility and clinical relevance, candidate predictors were subsequently entered into a multivariable Cox proportional hazards model while limiting model complexity according to the number of available outcome events. Internal validation was performed by bootstrap resampling, and regression coefficients were transformed into an exploratory individualized perioperative nomogram estimating 5-year tricuspid regurgitation recurrence-free survival. Results: Univariable analysis identified female sex, dyslipidemia, left ventricular ejection fraction < 45%, severe pre-operative TR, indexed tricuspid annular diameter and suture-based annuloplasty as predictors of recurrent TR. Multivariable analysis identified surgical repair strategy as the only independent predictor associated with recurrent TR, with suture-based annuloplasty showing a significantly higher recurrence risk than prosthetic ring annuloplasty. These variables were integrated into an exploratory individualized prediction model estimating 5-year recurrence-free survival: the FuTURe nomogram. Conclusions: Our findings confirm the association between prosthetic ring annuloplasty and a lower risk of recurrent TR, consistent with current evidence supporting ring implantation as the preferred repair strategy. Beyond identifying predictors of recurrence, the FuTURe study proposes an exploratory perioperative individualized prediction model intended to complement current guideline recommendations. Consistent with its acronym, the FuTURe study shifts the focus from immediate procedural success to the patient’s future clinical trajectory, highlighting the value of individualized recurrence-risk assessment from a lifetime management perspective.