Outcomes Following Lung Transplant for COVID-19-Related Complications in the US

IMPORTANCE: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. OBJECTIVE: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. EXPOSURES: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. MAIN OUTCOMES AND MEASURES: Overall survival and graft failure rates. RESULTS: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. CONCLUSIONS AND RELEVANCE: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies

Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms

Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. Methods: Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. Results: EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. Conclusions: In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential

Endovascular Treatment of Type A Aortic Dissection: A Systematic Review and Meta-Analysis Using Reconstructed Time-to-Event Data

Objective: The undisputed gold standard of treatment for type A aortic dissections (TAAD) is open surgery. Anecdotal reports have assessed thoracic endovascular aortic repair (TEVAR) as a last resort for highly selected candidates. The present study aims to evaluate endovascular outcomes in TAAD patients who are unsuitable for open surgery whilst having TEVAR-compatible aortic anatomy. Methods: A PRISMA-compliant systematic search of the PubMed, Scopus, and Cochrane databases was performed up to 19 May 2022. Time-to-event data were reconstructed using Kaplan–Meier curves from the source literature. Results: In 20 eligible studies, 311 patients underwent TEVAR for acute, subacute, or chronic TAAD. Mean age at the time of the operation was 60.70 ± 8.00 years and 75.48% (95% Confidence Interval [CI], 60.33–88.46%) of the included patients were males. Mean operative time was 169.40 ± 30.70 min. Overall, 0.44% (95% CI, 0.00–4.83%) of the cases were converted to salvage open surgery. Technical failure, stroke, and endoleaks occurred in 0.22%, 0.1%, and 8.52% of the cohort, respectively. Thirty-day postoperative complication rate was 7.08% (95% CI, 1.52–14.97%), whereas late complications developed in 16.89% (95% CI, 7.75–27.88%) of the patients. One-, three-, and five-year survival rates were estimated at 87.15%, 82.52% and 82.31%, respectively. Reintervention was required in 8.38% of the cohort over a mean follow-up of 32.40 ± 24.40 months. Conclusions: TEVAR seems to be feasible in highly selected patients with TAAD who cannot tolerate open surgery. Overcoming technical limitations and acquiring long-term data are warranted to safely define the place of endovascular treatment in the armamentarium of TAAD repair

Renal outcomes in valve-in-valve transcatheter versus redo surgical aortic valve replacement: A systematic review and meta-analysis

INTRODUCTION: Postoperative acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) remain common and significant complications of both transcatheter valve-in-valve aortic valve replacement (ViV-TAVR) and redo surgical aortic valve replacement (SAVR). Nevertheless, the understanding of renal outcomes in the population undergoing either redo SAVR or ViV-TAVR remains controversial. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles of ViV-TAVR versus redo SAVR in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to September 2021. Primary outcomes were AKI and RRT. Secondary outcomes were stroke, major bleeding, pacemaker implantation rate, operative mortality, and 30-day mortality. RESULTS: Our search yielded 5435 relevant studies. Eighteen studies met the inclusion criteria with a total of 11,198 patients. We found ViV-TAVR to be associated with lower rates of AKI, postoperative RRT, major bleeding, pacemaker implantation, operative mortality, and 30-day mortality. No significant difference was observed in terms of stroke rate. The mean incidence of AKI in ViV-TAVR was 6.95% (±6%) and in redo SAVR was 15.2% (±9.6%). For RRT, our data showed that VIV-TAVR to be 1.48% (±1.46%) and redo SAVR to be 8.54% (±8.06%). CONCLUSION: Renoprotective strategies should be put into place to prevent and reduce AKI incidence regardless of the treatment modality. Patients undergoing re-intervention for the aortic valve constitute a high-risk and frail population in which ViV-TAVR demonstrated it might be a feasible option for carefully selected patients. Long-term follow-up data and randomized control trials will be needed to evaluate mortality and morbidity outcomes between these 2 treatments

Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. METHODS: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel random effects method. RESULTS: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861-with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61-1.16; I(2): 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22-1.20; I(2): 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50-2.40; I(2): 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47-2.39; I(2): 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65-1.14; I(2): 0%). CONCLUSIONS: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation

Machine learning and artificial intelligence in cardiac transplantation: A systematic review

BACKGROUND: This review aims to systematically evaluate the currently available evidence investigating the use of artificial intelligence (AI) and machine learning (ML) in the field of cardiac transplantation. Furthermore, based on the challenges identified we aim to provide a series of recommendations and a knowledge base for future research in the field of ML and heart transplantation. METHODS: A systematic database search was conducted of original articles that explored the use of ML and/or AI in heart transplantation in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to November 2021. RESULTS: Our search yielded 237 articles, of which 13 studies were included in this review, featuring 463 850 patients. Three main areas of application were identified: (1) ML for predictive modeling of heart transplantation mortality outcomes; (2) ML in graft failure outcomes; (3) ML to aid imaging in heart transplantation. The results of the included studies suggest that AI and ML are more accurate in predicting graft failure and mortality than traditional scoring systems and conventional regression analysis. Major predictors of graft failure and mortality identified in ML models were: length of hospital stay, immunosuppressive regimen, recipient's age, congenital heart disease, and organ ischemia time. Other potential benefits include analyzing initial lab investigations and imaging, assisting a patient with medication adherence, and creating positive behavioral changes to minimize further cardiovascular risk. CONCLUSION: ML demonstrated promising applications for improving heart transplantation outcomes and patient-centered care, nevertheless, there remain important limitations relating to implementing AI into everyday surgical practices

Long‐Term Outcomes of Patients Undergoing Aortic Root Replacement With Mechanical Versus Bioprosthetic Valves: Meta‐Analysis of Reconstructed Time‐to‐Event Data

Background An aspect not so clear in the scenario of aortic surgery is how patients fare after composite aortic valve graft replacement (CAVGR) depending on the type of valve (bioprosthetic versus mechanical). We performed a study to evaluate the long‐term outcomes of both strategies comparatively. Methods and Results Pooled meta‐analysis of Kaplan‐Meier–derived time‐to‐event data from studies with follow‐up for overall survival (all‐cause death), event‐free survival (composite end point of cardiac death, valve‐related complications, stroke, bleeding, embolic events, and/or endocarditis), and freedom from reintervention. Twenty‐three studies met our eligibility criteria, including 11 428 patients (3786 patients with mechanical valves and 7642 patients with bioprosthetic valve). The overall population was mostly composed of men (mean age, 45.5–75.6 years). In comparison with patients who underwent CAVGR with bioprosthetic valves, patients undergoing CAVGR with mechanical valves presented no statistically significant difference in the risk of all‐cause death in the first 30 days after the procedure (hazard ratio [HR], 1.24 [95% CI, 0.95–1.60]; P=0.109), but they had a significantly lower risk of all‐cause mortality after the 30‐day time point (HR, 0.89 [95% CI, 0.81–0.99]; P=0.039) and lower risk of reintervention (HR, 0.33 [95% CI, 0.24–0.45]; P<0.001). Despite its increased risk for the composite end point in the first 6 years of follow‐up (HR, 1.41 [95% CI, 1.09–1.82]; P=0.009), CAVGR with mechanical valves is associated with a lower risk for the composite end point after the 6‐year time point (HR, 0.46 [95% CI, 0.31–0.67]; P<0.001). Conclusions CAVGR with mechanical valves is associated with better long‐term outcomes in comparison with CAVGR with bioprosthetic valves

Impact of prosthesis-patient mismatch after transcatheter aortic valve replacement : meta-analysis of kaplan-meier-derived individual patient data

Background: It remains controversial whether prosthesis-patient mismatch (PPM) (in general considered moderate if indexed effective orifice area is 0.65-0.85 cm2/m2 and severe when <0.65 cm2/m2) affects the outcomes after transcatheter aortic valve replacement (TAVR). Objectives: The purpose of this study is to evaluate the time-varying effects and association of PPM with the risk of overall mortality. Methods: Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of studies published by December 30, 2021. Results: In total, 23 studies met our eligibility criteria and included a total of 81,969 patients included in the Kaplan-Meier curves (19,612 with PPM and 62,357 without PPM). Patients with moderate/severe PPM had a significantly higher risk of mortality compared with those without PPM (HR: 1.09 [95% CI: 1.04-1.14]; P < 0.001). In the first 30 months after the procedure, mortality rates were significantly higher in the moderate/severe PPM group (HR: 1.1 [95% CI: 1.05-1.16]; P < 0.001). In contrast, the landmark analysis beyond 30 months yielded a reversal of the HR (0.83 [95% CI: 0.68-1.01]; P = 0.064), but without statistical significance. In the sensitivity analysis, although the authors observed that severe PPM showed higher risk of mortality in comparison with no PPM (HR: 1.25 [95% CI: 1.16-1.36]; P < 0.001), they did not observe a statistically significant difference for mortality between moderate PPM and no PPM (HR: 1.03 [95% CI: 0.96-1.10]; P = 0.398). Conclusions: Severe PPM, but not moderate PPM, was associated with higher risk of mortality following TAVR. These results provide support to implementation of preventive strategies to avoid severe PPM following TAV

Long-term outcomes of Ross procedure versus mechanical aortic valve replacement : meta-analysis of reconstructed time-to-event data

In the era of lifetime management of aortic valve disease, the Ross procedure emerged as an alternative to prosthetic heart valves for young adults; however, more long-term data are warranted. We performed a meta-analysis of reconstructed time-to-event data to compare long-term outcomes between the Ross procedure and mechanical aortic valve replacement (mAVR) in young adults. PubMed/MEDLINE, EMBASE and GoogleScholar were searched for studies comparing Ross procedure with mAVR that reported mortality/survival rates and/or reoperation rates accompanied by at least one Kaplan-Meier curve for any of the outcomes. Six observational studies (5 with propensity score matching) including 5024 patients (Ross: 1737; mAVR: 3287) met our inclusion criteria. Patients who underwent Ross had a significantly lower risk of mortality in the overall population (HR 0.38, 95%CI 0.30-0.49, P<0.001; median follow-up of 7.2 years) and in the propensity score matched cohorts (HR 0.55, 95%CI 0.42-0.73, P<0.001; median follow-up of 10.2 years); however, the incidence function for the cumulative risk of reoperation was higher for the Ross procedure (HR 1.91, 95%CI 1.36-2.70, P<0.001; median follow-up of 9.3 years). Data from observational studies suggest that the Ross procedure is associated with lower all-cause mortality compared with mAVR; however, there is a higher risk of reoperation. Besides serving as basis to inform patients about benefits and risks involved in this choice, these results call for further randomized clinical trials to determine whether the Ross procedure can achieve its potential benefits in young patients in need of AVR

Impact of paravalvular leak on outcomes after transcatheter aortic valve implantation : meta-analysis of Kaplan-Meier-derived individual patient data

Background Paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) is frequent and the impact of mild PVL on outcomes remains uncertain. Our study aimed to evaluate the impact of PVL on TAVI outcomes. Methods To analyze late outcomes of patients after TAVI according to the presence and severity of PVL, PubMed/MEDLINE, EMBASE and Google Scholar were searched for studies that reported rates of all-cause mortality/survival and/or rehospitalization and/or cardiovascular mortality accompanied by at least one Kaplan-Meier curve for any of these outcomes. We adopted a 2-stage approach to reconstruct individual patient data based on the published Kaplan-Meier graphs. Results Thirty-eight studies with Kaplan-Meier curves met our eligibility criteria including over 25,000 patients. Patients with any degree of PVL after TAVI had a significantly higher risk of overall mortality (hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.43-1.61; p < 0.001), rehospitalization (HR, 1.81; 95% CI, 1.54-2.12; p < 0.001), and cardiovascular mortality (HR, 1.52; 95% CI, 1.33-1.75; p < 0.001) over time. These findings remained consistent when we stratified the results for the methods of assessment of PVL (i.e., echocardiography vs. angiography) and PVL severity. Both moderate/severe PVL and mild PVL were associated with increased risk of overall mortality (p < 0.001), rehospitalization (p < 0.001), and cardiovascular mortality (p < 0.001) during follow-up. Conclusions Patients with PVL, even if mild, experience higher risk of all-cause mortality, rehospitalization, and cardiovascular mortality following TAVI. These findings provide support to the implementation of procedural strategies to prevent any degree of PVL at the time of TAVI