Cardiac Damage Staging Predicts Outcomes in Aortic Valve Stenosis After Aortic Valve Replacement: Meta-Analysis.

Background: The prognostic value of cardiac damage staging classification based on the extent of extravalvular damage has been proposed in moderate/severe aortic stenosis (AS). Objectives: The purpose of this study was to assess the association of cardiac damage staging with mortality across the spectrum of patients with AS following aortic surgical or transcatheter aortic valve replacement (AVR). Methods: We conducted a pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies published through February 2023. Results: In total, 16 studies (n = 14,499) met our eligibility criteria and included 12,282 patients with symptomatic severe AS and 2,217 patients with asymptomatic severe/moderate AS. For patients with symptomatic severe AS, all-cause mortality was 24.0%, 27.7%, 38.0%, 56.3%, and 57.3% at 5 years in patients with cardiac damage stage 0, 1, 2, 3, and 4, respectively (stage 0 as reference; HR in stage 1: 1.30 [95% CI: 1.03-1.64]; P = 0.029; stage 2: 1.74 [95% CI: 1.41-2.16]; P < 0.001; stage 3: 2.92 [95% CI: 2.35-3.64]; P < 0.001, and stage 4: 3.51 [95% CI: 2.79-4.41]; P < 0.001). For patients with asymptomatic moderate/severe AS, all-cause mortality was 19.3%, 36.9%, 51.7%, and 67.8% at 8 years in patients with cardiac damage stage 0, 1, 2, and 3 to 4, respectively (HR in stage 1: 1.70 [95% CI: 1.21-2.38]; P = 0.002; stage 2: 2.20 [95% CI: 1.60-3.02]; P < 0.001; and stage 3 to 4: 3.90 [95% CI: 2.79-5.47]; P < 0.001). Conclusions: In patients undergoing AVR across the symptomatic and severity spectrum of AS, cardiac damage staging at baseline has important prognostic implications. This pooled meta-analysis in patients undergoing AVR suggests that staging of baseline cardiac damage could be considered for timing and selection of therapy in patients with moderate or severe AS to determine the need for earlier AVR or adjunctive pharmacotherapy to prevent irreversible cardiac damage and improve the long-term prognosis.

Late Outcomes After Transcatheter Aortic Valve Implantation with Balloon-Versus Self-Expandable Valves: Meta-Analysis of Reconstructed Time-To-Event Data.

Self-expanding valves (SEV) and balloon-expandable valves (BEV) for transcatheter aortic valve implantation (TAVI) have their own features. There is a growing interest in long-term outcomes with the adoption of lifetime management in younger patients. To evaluate late outcomes in TAVI with SEV versus BEV, we performed a study-level meta-analysis of reconstructed time-to-event data published by May 31, 2023. We found no statistically significant difference in all-cause death after TAVI with SEV versus BEV. Randomized controlled trials are warranted to validate our results.

Long-term outcomes of total arch replacement with bilateral antegrade cerebral perfusion using the "arch first" approach.

OBJECTIVE: To report outcomes of total arch replacement (TAR) with hypothermic circulatory arrest and bilateral antegrade cerebral perfusion (bACP) using an "arch first" approach for acute Type A aortic dissection (ATAAD). The "arch first" approach involved revascularization of the aortic arch branch vessels with uninterrupted ACP, before lower body circulatory arrest, while the patient was cooling. METHODS: This was an observational study of aortic surgeries from 2010 to 2021. All patients who underwent TAR with bACP for ATAAD were included. Short-term and long-term outcomes were reported utilizing descriptive statistics and Kaplan-Meier survival estimation. RESULTS: A total of 215 patients were identified who underwent TAR + bACP for ATAAD. Age was 59.0 [49.0-67.0] years and 35.3% were female. 73 patients (34.0%) underwent a concomitant aortic root replacement, 188 (87.4%) had aortic cannulation, circulatory arrest time was 37.0 [26.0-52.0] minutes, and nadir temperature was 20.8 [19.4-22.5] degrees Celsius. 35 patients (16.3%) had operative mortality (STS definition), 17 (7.9%) had a new stroke, 79 (36.7%) had prolonged mechanical ventilation (>24 h), 35 (16.3%) had acute renal failure (by RIFLE criteria), and 128 (59.5%) had blood product transfusions. One-year survival was 77.1%, while 5-years survival was 67.1%. During follow-up, there were 23 (10.7%) reinterventions involving the descending thoracic aorta - either thoracic endovascular aortic repair or open thoracoabdominal aortic replacement. CONCLUSIONS: Among patients with ATAAD, short-term postoperative outcomes after TAR + bACP using the "arch first" approach are acceptable. Moreover, this operative strategy may furnish long-term durability, with a reasonably low reintervention rate and satisfactory overall survival.

Long-Term Outcomes of Tricuspid Valve Replacement With Mechanical Versus Tissue Valves: Meta-Analysis of Reconstructed Time-to-Event Data.

Tricuspid valve replacement (TVR) with mechanical versus tissue valves remains a controversial subject. To evaluate the long-term effects of types of valves on patient-relevant outcomes, we performed a systematic review with meta-analysis of reconstructed time-to-event data of studies published by March 15, 2024 (according to referred the Reporting Items for Systematic Reviews and Meta-analyses guidelines). A total of 21 studies met our eligibility criteria and included 7,166 patients (mechanical: 2,495 patients, 34.8%). Patients who underwent mechanical TVR had a lower risk of death than those who received a tissue valve (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70 to 0.84, p <0.001). Mechanical TVR was associated with lifetime gain, as evidenced by the restricted mean survival time, which was 2.2 years longer in patients who underwent TVR with mechanical valves (12.4 vs 10.2 years, p <0.001). Our landmark analysis for reoperations revealed the following: from the time point 0 to 7 years, we found no difference in the risk of reoperation between mechanical and tissues valves (HR 0.98, 95% CI 0.60 to 1.61, p = 0.946); however, from the time point 7 years onward, we found that mechanical TVR had a lower risk of reoperation in the follow-up (HR 0.24, 95% CI 0.08 to 0.72, p = 0.001). The meta-regression analysis demonstrated a modulating effect of atrial fibrillation on the association between mechanical valves and mortality; the HRs for all-cause death tended to decrease in the presence of populations with a larger proportion of atrial fibrillation (p = 0.018). In conclusion, our results suggest that TVR with mechanical valves, whenever considered clinically reasonable and accepted by patients as an option, can offer a better long-term survival and lower risk of reoperation in the long run.

Overcoming prosthesis-patient mismatch with transcatheter aortic valve replacement.

For decades, surgeons have recognized the risk of prosthesis-patient mismatch (PPM) when treating aortic stenosis (AS) with surgical aortic valve replacement (SAVR). The concept of PPM-or placing a valve that is too small for the cardiac output requirements of the patient-has been associated with worse patient outcomes, including increased risk of death. Transcatheter aortic valve replacement (TAVR) has become the standard treatment for most patients with severe symptomatic AS and is associated with improved hemodynamics and lower risks of PPM. Larger surgical valves, stentless, and sutureless technology, and surgical aortic annulus enlargement (AAE) have been employed to avoid severe PPM. However, especially in the small aortic annulus (SAA), TAVR may provide a benefit. Understanding who is at risk for PPM requires preplanning, and cardiac-gated computed tomography (CT) imaging is the standard of care when considering TAVR. It should be standard for all patients with AS. Once SAA is identified, the risk of PPM can be calculated, and an informed decision made on whether to proceed with SAVR or TAVR. In the current TAVR era, younger patients are treated with TAVR driven by patient preference, but with little long-term data to support the practice. Selecting the best valve for the patient is a multifactorial decision often nuanced by anatomical considerations, hemodynamic and durability expectations, and decisions regarding lifetime management that may include placing a second valve. Although PPM may be only one of the factors to consider, the association with elevated mean gradients and worse outcomes certainly makes TAVR a good solution for many patients.

Central versus peripheral cannulation for acute type A aortic dissection: A meta-analysis of over 14,000 patients.

OBJECTIVE: The optimal cannulation strategy for patients with acute type A aortic dissections (ATAAD) is unclear. METHODS: A systematic search was performed to identify all studies comparing aortic and non-aortic cannulation in patients undergoing ATAAD repair. The primary endpoint was overall survival. The secondary endpoints were operative mortality, postoperative stroke, renal failure, renal replacement therapy, paraplegia, and mesenteric ischemia. Pooled meta-analyses with aggregated and reconstructed time-to-event data were performed. RESULTS: Twenty-three studies were included (aortic: 3904; non-aortic: 10,719). Ten-year overall survival was 61.1 â€‹% and 58.4 â€‹% for aortic and non-aortic cannulation, respectively (HR 1.07; 95 â€‹% CI 0.92-1.25; p â€‹= â€‹0.38). No statistically significant difference was observed for operative mortality (p â€‹= â€‹0.10), stroke (p â€‹= â€‹0.89), renal failure (p â€‹= â€‹0.83), or renal replacement therapy (p â€‹= â€‹0.77). CONCLUSION: Patients undergoing surgery for ATAAD can undergo aortic cannulation with similar outcomes to those who undergo non-aortic cannulation.

Moderate Aortic Valve Stenosis Is Associated With Increased Mortality Rate and Lifetime Loss: Systematic Review and Meta-Analysis of Reconstructed Time-to-Event Data of 409 680 Patients.

BACKGROUND: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). METHODS AND RESULTS: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P<0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P<0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P<0.001; and 1.9 years, P<0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. CONCLUSIONS: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Machine-learning approaches for risk prediction in transcatheter aortic valve implantation: Systematic review and meta-analysis.

OBJECTIVES: With the expanding integration of artificial intelligence (AI) and machine learning (ML) into the structural heart domain, numerous ML models have emerged for the prediction of adverse outcomes after transcatheter aortic valve implantation (TAVI). We aim to identify, describe, and critically appraise ML prediction models for adverse outcomes after TAVI. Key objectives consisted in summarizing model performance, evaluating adherence to reporting guidelines, and transparency. METHODS: We searched PubMed, SCOPUS, and Embase through August 2023. We selected published machine learning models predicting TAVI outcomes. Two reviewers independently screened articles, extracted data, and assessed the study quality according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcomes included summary C-statistics and model risk of bias assessed with the Prediction Model Risk of Bias Assessment Tool. C-statistics were pooled using a random-effects model. RESULTS: Twenty-one studies (118,153 patients) employing various ML algorithms (76 models) were included in the systematic review. Predictive ability of models varied: 11.8% inadequate (C-statistic <0.60), 26.3% adequate (C-statistic 0.60-0.70), 31.6% acceptable (C-statistic 0.70-0.80), and 30.3% demonstrated excellent (C-statistic >0.80) performance. Meta-analyses revealed excellent predictive performance for early mortality (C-statistic: 0.81; 95% confidence interval [CI], 0.65-0.91), acceptable performance for 1-year mortality (C-statistic: 0.76; 95% CI, 0.67-0.84), and acceptable performance for predicting permanent pacemaker implantation (C-statistic: 0.75; 95% CI, 0.51-0.90). CONCLUSIONS: ML models for TAVI outcomes exhibit adequate-to-excellent performance, suggesting potential clinical utility. We identified concerns in methodology and transparency, emphasizing the need for improved scientific reporting standards.

Phase-specific survival after endovascular versus open surgical repair of descending thoracic aortic aneurysm.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has gained preference over open surgical repair (OSR) as the intervention of choice for patients with descending thoracic aortic aneurysm (DTA). This study aimed to compare the outcomes of patients with DTA undergoing OSR and TEVAR with contemporary findings. EVIDENCE ACQUISITION: A comprehensive search of MEDLINE and EMBASE databases was conducted to identify relevant randomized controlled trials or studies utilizing propensity-score analysis or reporting risk-adjusted outcomes. The search was performed up until March 2023. EVIDENCE SYNTHESIS: Eight studies met the inclusion criteria, including 4 studies using propensity-score matching and four studies reporting risk-adjusted outcomes, comprising 14,873 patients with DTA undergoing OSR (N.=10,882) and TEVAR (N.=3991). Operative mortality was similar between the two interventions (odds ratio 0.92, 95% CI 0.70-1.21, P=0.57, I2=0%). However, overall long-term mortality was significantly higher after TEVAR compared to OSR (Hazard Ratio [HR] 1.30, 95% CI 1.05-1.59, P=0.01, I2=0%). Phase-specific analysis revealed comparable risks of mortality within 1 year and between one and two years after interventions, while the risk of mortality was significantly higher after TEVAR compared to OSR beyond two years (HR 1.77, 95% CI, 1.19-2.63, P=0.01. I2=0%). CONCLUSIONS: This study demonstrated comparable operative mortality between OSR and TEVAR, but higher long-term mortality associated with TEVAR in patients with DTA. The phase-specific analysis highlighted the survival advantage of OSR beyond 2 years. These findings suggest a need for reconsidering OSR indications in the management of DTA.

Acute Aortic Dissection After Transcatheter Aortic Valve Replacement.

Acute aortic dissection (AAD) is a rare and potentially fatal complication associated with transcatheter aortic valve replacement (TAVR). Owing to the paucity of existing institutional data, we sought to assess the incidence of postimplant AAD in patients who underwent TAVR at a single institution. All patients who underwent TAVR from 2013 to 2022 were retrospectively reviewed to identify those who possessed clinical or radiologic evidence of AAD after TAVR. Follow-up and survival data were retrieved for all included patients. A total of 4,317 patients underwent TAVR, of whom 9 (0.2%) sustained an AAD. These patients had a mean age of 80 years (range 53 to 92), mean Society of Thoracic Surgeons 30-day mortality risk of 5.7% (2.4% to 16.7%), and mean effective aortic valve area of 0.8 cm2 (0.4 to 1.5 cm2). Preoperative maximum aortic diameter was 3.9 cm (2.6 to 4 cm). Of these 9 patients, 6 (67%) showed evidence of Stanford type A dissection, whereas 3 (33%) were diagnosed with Stanford type B dissection. The most common causes of dissection were posterior annular rupture by the transcatheter valve (THV) (44%) and THV embolization or "pop-out" into the ascending aorta (22%). A total of 6 patients (66.7%), comprising 5 type A (55.6%) and 1 type B (11.1%) aortic dissections, died within 30 days of AAD. The median time to follow-up in those surviving TAVR with intraoperative AAD was 1,042 days (range: 648 to 2,666). Surviving patients were managed through thoracic endovascular aortic repair and medical management. In conclusion, in this highly selected cohort of patients, our experience indicates that AAD after TAVR is a rare but often lethal intraprocedural sequela of THV implantation, especially in cases of type A aortic dissection.

External validation of the ARCH score in patients undergoing aortic arch reconstruction under circulatory arrest.

BACKGROUND: Aortic arch surgery with hypothermic circulatory arrest (HCA) carries a higher risk of morbidity and mortality compared to routine cardiac surgical procedures. The newly developed ARCH (arch reconstruction under circulatory arrest with hypothermia) score has not been externally validated. We sought to externally validate this score in our local population. METHODS: All consecutive open aortic arch surgeries with HCA performed between 2014 and 2023 were included. Univariable and multivariable analyses were performed. Model discrimination was assessed by the C-statistic with 95% confidence intervals as part of the receiver operating characteristic (ROC) curve analysis. Model performance was visualized by a calibration plot and quantified by the Brier score. RESULTS: A total of 760 patients (38.3% females) were included. The mean age was 61 (±13.6) years, with 56.4% of patients' age >60 years. The procedures were carried out mostly emergently or urgently (59.6%). Total arch replacement was performed in 32.5% of the patients, and aortic root procedures were carried out in 74.6%. In-hospital death occurred in 64 patients (8.4%), and stroke occurred in 5.4%. The C-statistic revealed a low discriminatory ability for predicting in-hospital mortality (area under the ROC curve, 0.62; 95% confidence interval, 0.54-0.69; P = .002); however, model calibration was found to be excellent (Brier score of 0.07). CONCLUSIONS: The ARCH score for in-hospital mortality showed low discriminatory ability in our local population, although with excellent ability for prediction of mortality.

Extracorporeal life support after surgical repair for acute type a aortic dissection: A systematic review and meta-analysis.

BACKGROUND: The use of extracorporeal life support (ECLS) in patients after surgical repair for acute type A aortic dissection (ATAAD) has not been well documented. METHODS: We performed a systematic review and meta-analysis to assess the outcomes of ECLS after surgery for ATAAD with data published by October 2023 in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The protocol was registered in PROSPERO (CRD42023479955). RESULTS: Twelve observational studies met our eligibility criteria, including 280 patients. Mean age was 55.0 years and women represented 25.3% of the overall population. Although the mean preoperative left ventricle ejection fraction was 59.8%, 60.8% of patients developed left ventricle failure and 34.0% developed biventricular failure. Coronary involvement and malperfusion were found in 37.1% and 25.6%, respectively. Concomitant coronary bypass surgery was performed in 38.5% of patients. Regarding ECLS, retrograde flow (femoral) was present in 39.9% and central cannulation was present in 35.4%. In-hospital mortality was 62.8% and pooled estimate of successful weaning was 50.8%. Neurological complications, bleeding and renal failure were found in 25.9%, 38.7%, and 65.5%, respectively. CONCLUSION: ECLS after surgical repair for ATAAD remains associated with high rates of in-hospital death and complications, but it still represents a chance of survival in critical situations. ECLS remains a salvage attempt and surgeons should not try to avoid ECLS at all costs after repairing an ATAAD case.

Can we safely expand the donation after circulatory death donor heart pool by extending the donor age limit?

OBJECTIVE: This study evaluates the impact of donor age on outcomes following donation after circulatory death heart transplantation. METHODS: The United Network for Organ Sharing registry was queried to analyze adult recipients who underwent isolated donation after circulatory heart transplantation from January 1, 2019, to September 30, 2023. The cohort was stratified into 2 groups according to donor age, where advanced donor age was defined as 40 years or more. Outcomes were 90-day and 1-year post-transplant survival. Propensity score matching was performed. Subgroup analysis was performed to evaluate the effects of recipient age on 90-day survival among the recipients with advanced-age donors. RESULTS: A total of 994 recipients were included in the study period, and 161 patients (17.1%) received allografts from advanced-age donors. During the study period, the annual incidence of donation after circulatory heart transplantation with advanced-age donors substantially increased. The recipients with advanced-age donors had similar 90-day and 1-year post-transplant survivals compared with the recipients with younger donors. The comparable 90-day survival persisted in a propensity score-matched comparison. In the subgroup analysis among the recipients with advanced-age donors, the recipients aged 60 years or more had significantly reduced 90-day survival compared with the recipients aged less than 60 years. CONCLUSIONS: The use of appropriately selected donation after circulatory donors aged 40 years or more has similar survival compared with that of younger donors. With careful candidate risk stratification and selection, consideration of using donation after circulatory donors aged more than 40 years may further ameliorate ongoing organ shortage with comparable early post-transplant outcomes.

Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

Transcatheter versus surgical aortic valve replacement for severe aortic valve stenosis: Meta-analysis with trial sequential analysis.

OBJECTIVES: Randomized controlled trials comparing transcatheter aortic valve implantation with surgical aortic valve replacement demonstrate conflicting evidence, particularly in low-risk patients. We aim to reevaluate the evidence using trial sequential analysis, balancing type I and II errors, and compare with conventional meta-analysis. METHODS: Databases were searched for randomized controlled trials, which were divided into higher-risk and lower-risk randomized controlled trials according to a pragmatic risk classification. Primary outcomes were death and a composite end point of death or disabling stroke assessed at 1 year and maximum follow-up. Conventional meta-analysis and trial sequential analysis were performed, and the required information size was calculated considering a type I error of 5% and a power of 90%. RESULTS: Eight randomized controlled trials (n = 5274 higher-risk and 3661 lower-risk patients) were included. Higher-risk trials showed no significant reduction in death at 1 year with transcatheter aortic valve implantation (relative risk, 0.93, 95% CI, 0.81-1.08, P = .345). Lower-risk trials suggested lower death risk on conventional meta-analysis (relative risk, 0.67, 95% CI, 0.47-0.96, P = .031), but trial sequential analysis indicated potential spurious evidence (P = .116), necessitating more data for conclusive benefit (required information size = 5944 [59.8%]). For death or disabling stroke at 1 year, higher-risk trials lacked evidence (relative risk, 0.90, 95% CI, 0.79-1.02, P = .108). In lower-risk trials, transcatheter aortic valve implantation indicated lower risk in conventional meta-analysis (relative risk, 0.68, 95% CI, 0.50-0.93, P = .014), but trial sequential analysis suggested potential spurious evidence (P = .053), necessitating more data for conclusive benefit (required information size = 5122 [69.4%]). Follow-up results provided inconclusive evidence for both primary outcomes across risk categories. CONCLUSIONS: Conventional meta-analysis methods may have prematurely declared an early reduction of negative outcomes after transcatheter aortic valve implantation when compared with surgical aortic valve replacement.

Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy.

BACKGROUND: Preclinical studies have shown the therapeutic potential of VEGF-B (vascular endothelial growth factor B) in revascularization of the ischemic myocardium, but the associated cardiac hypertrophy and adverse side effects remain a concern. To understand the importance of endothelial proliferation and migration for the beneficial versus adverse effects of VEGF-B in the heart, we explored the cardiac effects of autocrine versus paracrine VEGF-B expression in transgenic and gene-transduced mice. METHODS: We used single-cell RNA sequencing to compare cardiac endothelial gene expression in VEGF-B transgenic mouse models. Lineage tracing was used to identify the origin of a VEGF-B-induced novel endothelial cell population and adeno-associated virus-mediated gene delivery to compare the effects of VEGF-B isoforms. Cardiac function was investigated using echocardiography, magnetic resonance imaging, and micro-computed tomography. RESULTS: Unlike in physiological cardiac hypertrophy driven by a cardiomyocyte-specific VEGF-B transgene (myosin heavy chain alpha-VEGF-B), autocrine VEGF-B expression in cardiac endothelium (aP2 [adipocyte protein 2]-VEGF-B) was associated with septal defects and failure to increase perfused subendocardial capillaries postnatally. Paracrine VEGF-B led to robust proliferation and myocardial migration of a novel cardiac endothelial cell lineage (VEGF-B-induced endothelial cells) of endocardial origin, whereas autocrine VEGF-B increased proliferation of VEGF-B-induced endothelial cells but failed to promote their migration and efficient contribution to myocardial capillaries. The surviving aP2-VEGF-B offspring showed an altered ratio of secreted VEGF-B isoforms and developed massive pathological cardiac hypertrophy with a distinct cardiac vessel pattern. In the normal heart, we found a small VEGF-B-induced endothelial cell population that was only minimally expanded during myocardial infarction but not during physiological cardiac hypertrophy associated with mouse pregnancy. CONCLUSIONS: Paracrine and autocrine secretions of VEGF-B induce expansion of a specific endocardium-derived endothelial cell population with distinct angiogenic markers. However, autocrine VEGF-B signaling fails to promote VEGF-B-induced endothelial cell migration and contribution to myocardial capillaries, predisposing to septal defects and inducing a mismatch between angiogenesis and myocardial growth, which results in pathological cardiac hypertrophy.

Late Outcomes of Surgery Versus Medical Therapy in Patients With Type A Aortic Intramural Hematoma: Meta-Analysis of Reconstructed Time-to-Event Data.

The effect of an initial surgical approach (in comparison with initial medical therapy) in acute type A intramural hematoma remains insufficiently explored. We designed a pooled analysis of Kaplan-Meier-derived individual patient data from studies with follow-up for overall survival (all-cause death). Restricted mean survival time was calculated to evaluate lifetime gain or loss. The Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-I) was used to assess risk of bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to assess certainty of evidence. Eight studies met our eligibility criteria, including a total of 654 patients (311 patients treated with surgery and 343 patients treated with medical therapy alone). All the studies were non-randomized and observational. The median follow-up was 4.6 years (interquartile range 1.0 to 7.7). Patients who underwent surgery had a significantly lower risk of mortality compared with patients receiving medical therapy alone (hazard ratio 0.51, 95% confidence interval 0.35 to 0.74, p <0.001). The restricted mean survival time was overall 1.1 years greater with surgery compared with medical therapy, and this difference was statistically significant (p <0.001), which means that surgery is associated with lifetime gain. The overall risk of bias (ROBINS-I) was considered moderate-to-serious and the certainty of evidence (GRADE) was deemed to be low. In conclusion, in the overall follow-up, surgery as the initial approach was associated with better late survival and lifetime gain in comparison with medical therapy alone in the setting of acute type A aortic intramural hematoma; however, high-quality randomized trials are warranted to establish the efficacy of the surgical strategy.

Axillary vs Femoral Arterial Cannulation in Acute Type A Dissection: International Multicenter Data.

BACKGROUND: Cannulation strategy in acute type A dissection (ATAD) varies widely without known gold standards. This study compared ATAD outcomes of axillary vs femoral artery cannulation in a large cohort from the International Registry of Acute Aortic Dissection (IRAD). METHODS: The study retrospectively reviewed 2145 patients from the IRAD Interventional Cohort (1996-2021) who underwent ATAD repair with axillary or femoral cannulation (axillary group: n = 1106 [52%]; femoral group: n = 1039 [48%]). End points included the following: early mortality; neurologic, respiratory, and renal complications; malperfusion; and tamponade. All outcomes are presented as axillary with respect to femoral. RESULTS: The proportion of patients younger than 70 years in both groups was similar (n = 1577 [74%]), as were bicuspid aortic valve, Marfan syndrome, and previous dissection. Patients with femoral cannulation had slightly more aortic insufficiency (408 [55%] vs 429 [60%]; P = .058) and coronary involvement (48 [8%] vs 70 [13%]; P = .022]. Patients with axillary cannulation underwent more total aortic arch (156 [15%] vs 106 [11%]; P = .02) and valve-sparing root replacements (220 [22%] vs 112 [12%]; P < .001). More patients with femoral cannulation underwent commissural resuspension (269 [30.9%] vs 324 [35.3%]; P = .05). Valve replacement rates were not different. The mean duration of cardiopulmonary bypass was longer in the femoral group (190 [149-237] minutes vs 196 [159-247] minutes; P = .037). In-hospital mortality was similar between the axillary (n = 165 [15%]) and femoral (n = 149 [14%]) groups (P = .7). Furthermore, there were no differences in stroke, visceral ischemia, tamponade, respiratory insufficiency, coma, or spinal cord ischemia. CONCLUSIONS: Axillary cannulation is associated with a more stable ATAD presentation, but it is a more extensive intervention compared with femoral cannulation. Both procedures have equivalent early mortality, stroke, tamponade, and malperfusion outcomes after statistical adjustment.