Late outcomes of valve-in-valve transcatheter aortic valve implantation versus re-replacement: Meta-analysis of reconstructed time-to-event data.

AIMS: To evaluate all-cause mortality in ViV-TAVI versus redo SAVR in patients with failed bioprostheses. METHODS: Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of non-randomized studies published by September 30, 2021. RESULTS: Ten studies met our eligibility criteria and included a total of 3345 patients (1676 patients underwent ViV-TAVI and 1669 patients underwent redo SAVR). Pooling all the studies, ViV-TAVI showed a lower risk of all-cause mortality in the first 44 days [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.49-0.93, P = 0.017], with an HR reversal after 197 days favoring redo SAVR (HR 1.53; 95% CI 1.22-1.93; P < 0.001). Pooling only the matched populations (1143 pairs), ViV-TAVI showed a lower risk of all-cause mortality in the first 55 days [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89, P < 0.001], with a reversal HR after 212 days favoring redo SAVR (HR 1.57; 95% CI 1.22-2.03; P < 0.001). The Cox regression model showed a statistically significant association of prosthesis-patient mismatch (PPM) with all-cause mortality during follow-up for ViV-TAVI (HR 1.03 per percentage increase in the study- and treatment arm-level proportion of PPM, 95% 1.02-1.05, P < 0.001). CONCLUSION: ViV-TAVI is associated with a strong protective effect immediately after the procedure in comparison with redo SAVR, however, this initial advantage reverses over time and redo SAVR seems to be a protective factor for all-cause mortality after 6 months. Considering that these results are the fruit of pooling data from observational studies, they should be interpreted with caution and trials are warranted.

Long-term outcomes of total arch replacement versus proximal aortic replacement in acute type A aortic dissection: Meta-analysis of Kaplan-Meier-derived individual patient data.

OBJECTIVES: To evaluate the long-term outcomes of a conservative approach (with proximal aortic replacement with or without hemiarch replacement) versus an aggressive approach (with total aortic arch replacement) in the treatment of acute type A aortic dissection (ATAAD). METHODS: We performed a pooled analysis of Kaplan-Meier-derived individual patient data from studies with follow-up comparing the aforementioned approaches to treat patients with ATAAD. RESULTS: Eighteen studies met our eligibility criteria, comprising 5243 patients with follow-up (Conservative: 3676 patients; Aggressive: 1567 patients). We observed a statistically significant difference in overall survival favoring the aggressive approach (hazard ratios [HR] 0.86, 95% confidence interval [CI] 0.76-0.98, p = .022), but no statistically significant difference in the risk of reoperation (HR 0.89, 95% CI 0.66-1.2, p = .439) in the overall follow-up. Landmark analyses revealed that, in the first 3 months after the procedure, mortality rates were comparable between conservative and aggressive approaches (HR 1.04, 95% CI 0.88-1.24, p = .627), but the results beyond 3 months showed improved survival in patients undergoing the aggressive surgical procedure (HR 0.71, 95% CI 0.59-0.85, p < .001). The landmark analyses also revealed that, in the first 7 years after the procedure, reoperation rates were comparable between the approaches (HR 1.03, 95% CI 0.76-1.40, p = .848), but the results beyond 7 years showed a lower risk of reoperation in patients undergoing the aggressive surgical procedure (HR 0.10, 95% CI 0.01-0.75, p = .025). CONCLUSION: The aggressive approach seems to confer better long-term survival and lower risk of the need for reoperation in the follow-up of patients treated for ATAAD.

Cardiac Arrest Risk During Acute Infections: Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-Mediated Effects on Potassium Channel Expression.

BACKGROUND: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression. METHODS: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. RESULTS: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. CONCLUSIONS: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.