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.

Reduction in Insulin Uncovers a Novel Effect of VEGFB on Cardiac Substrate Utilization.

BACKGROUND: The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)-mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown. METHODS: VEGFB transgenic (Tg) rats were generated by using the α-myosin heavy chain promoter to drive cardiomyocyte-specific overexpression. To measure coronary LPL activity, Langendorff hearts were perfused with heparin. In vivo positron emission tomography imaging with [18F]-triglyceride-fluoro-6-thia-heptadecanoic acid and [11C]-palmitate was used to determine cardiac FA uptake. Mitochondrial FA oxidation was evaluated by high-resolution respirometry. Streptozotocin was used to induce diabetes, and cardiac function was monitored using echocardiography. RESULTS: In Tg hearts, the vectorial transfer of LPL to the vascular lumen is obstructed, resulting in LPL buildup within cardiomyocytes, an effect likely due to coronary vascular development with its associated augmentation of insulin action. With insulin insufficiency following fasting, VEGFB acted unimpeded to facilitate LPL movement and increase its activity at the coronary lumen. In vivo PET imaging following fasting confirmed that VEGFB induced a greater FA uptake to the heart from circulating lipoproteins as compared with plasma-free FAs. As this was associated with augmented mitochondrial oxidation, lipid accumulation in the heart was prevented. We further examined whether this property of VEGFB on cardiac metabolism could be useful following diabetes and its associated cardiac dysfunction, with attendant loss of metabolic flexibility. In Tg hearts, diabetes inhibited myocyte VEGFB gene expression and protein secretion together with its downstream receptor signaling, effects that could explain its lack of cardioprotection. CONCLUSIONS: Our study highlights the novel role of VEGFB in LPL-derived FA supply and utilization. In diabetes, loss of VEGFB action may contribute toward metabolic inflexibility, lipotoxicity, and development of diabetic cardiomyopathy.

Radial artery vs right internal mammary artery as a second conduit during coronary artery bypass grafting.

OBJECTIVE: To compare the clinical outcomes of radial artery (RA) grafts during CABG to those of right internal mammary artery (RIMA) grafts. METHODS: This was a retrospective, single-institution cohort study of isolated CABG with multiple grafts between 2010-2022. To balance graft cohorts, propensity score matching (PSM) was performed using a 1:1 match ratio. Long-term postoperative survival was compared among RA and RIMA groups. Similarly, major adverse cardiac and cerebrovascular events (MACCE) were compared among both cohorts, with MACCE comprising death, myocardial infarction (MI), coronary revascularization, and stroke. Kaplan-Meier estimation was performed for mortality, while cumulative incidence estimation was utilized for MACCE. RESULTS: A total of 8,774 patients underwent CABG. Of those, 1,674 (19.1%) patients who underwent multiarterial CABG were included in this analysis. 326 (19.5%) patients received RA grafts and 1,348 (80.5%) received RIMA grafts. PSM yielded a cohort of 323 RA patients and 323 RIMA patients. After matching, groups were well-balanced across all baseline variables. No significant differences were observed in immediate postoperative complications or long-term survival, with 5-year survival estimates of 89.5% for the RA group vs 90.1% for the RIMA group. There was a nonsignificant trend toward a higher incidence of MACCE at 5 years in the RA group compared to the RIMA group (31.3% in the RA group vs 24.1% in the RIMA group), especially after 1-year follow-up (21.6% in the RA group vs 15.1% in the RIMA group). Specifically, for RA patients, there were higher rates of repeat revascularization in the 5-year postoperative period (14.7% in the RA group vs 5.3% in the RIMA group), particularly in the territory revascularized by the RA during the index operation (45.7% in the RA group vs 10.3% in the RIMA group). CONCLUSION: Overall, RA and RIMA secondary conduits for CABG were associated with comparable immediate postoperative complications, 5-year MACCE, and 5-year survival after PSM. RA grafting was associated with significantly higher rates of repeat coronary revascularization at 5 years, specifically in the territory revascularized by the RA during the index operation.

Five Year Results of Endovascular versus Medical Therapy in Acute Type B Aortic Intramural Haematoma: Meta-Analysis of Reconstructed Time to Event Data.

OBJECTIVE: To evaluate outcomes in the follow up of thoracic endovascular aortic repair (TEVAR) vs. medical therapy in patients with acute type B aortic intramural haematoma (IMH). DATA SOURCES: The following sources were searched for articles meeting the inclusion criteria and published by July 2023: PubMed/MEDLINE, EMBASE, CENTRAL/CCTR (Cochrane Controlled Trials Register). REVIEW METHODS: This systematic review with pooled meta-analysis of time to event data followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and its protocol was registered on the public platform PROSPERO (CRD42023456222). The following were analysed: overall survival (all cause mortality), aortic related mortality, and restricted mean survival time. Certainty of evidence was evaluated through the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. RESULTS: Eight studies met the eligibility criteria, including 1 015 patients (440 in the TEVAR group and 575 in the medical therapy group). All studies were observational, and the pooled cohort had a median follow up of 5.1 years. Compared with patients who received medical therapy alone, those who underwent TEVAR had a statistically significantly lower risk of all cause death (HR 0.44, 95% CI 0.30 - 0.65; p < .001; GRADE certainty: low), lower risk of aortic related death (HR 0.04, 95% CI 0.01 - 0.31; p = .002; GRADE certainty: low) and lifetime gain (restricted mean survival time was overall 201 days longer with TEVAR; p < .001). CONCLUSION: Thoracic endovascular aortic repair may be associated with lower risk of all cause and aortic related death compared with medical therapy in patients with acute type B IMH; however, the underlying data are not strong enough to draw robust clinical conclusions. Randomised controlled trials with large sample sizes and longer follow up are warranted to elucidate this question.

Intravenous Methadone versus Intrathecal Morphine as Part of an Enhanced Recovery After Cardiac Surgery Protocol on Postoperative Pain and Outcomes: A Retrospective Cohort Study.

OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.

Role of Intraoperative Neuromonitoring to Predict Postoperative Delirium in Cardiovascular Surgery.

OBJECTIVE: Postoperative delirium (POD) can occur in up to 50% of older patients undergoing cardiovascular surgery, resulting in hospitalization and significant morbidity and mortality. This study aimed to determine whether intraoperative neurophysiologic monitoring (IONM) modalities can be used to predict delirium in patients undergoing cardiovascular surgery. DESIGN: Adult patients undergoing cardiovascular surgery with IONM between 2019 and 2021 were reviewed retrospectively. Delirium was assessed multiple times using the Intensive Care Delirium Screening Checklist (ICDSC). Patients with an ICDSC score ≥4 were considered to have POD. Significant IONM changes were evaluated based on a visual review of electroencephalography (EEG) and somatosensory evoked potentials data and documentation of significant changes during surgery. SETTING: University of Pittsburgh Medical Center hospitals. PARTICIPANTS: Patients 18 years old and older undergoing cardiovascular surgery with IONM monitoring. MEASUREMENTS AND MAIN RESULTS: Of the 578 patients undergoing cardiovascular surgery with IONM, 126 had POD (21.8%). Significant IONM changes were noted in 134 patients, of whom 49 patients had delirium (36.6%). In contrast, 444 patients had no IONM changes during surgery, of whom 77 (17.3%) patients had POD. Upon multivariate analysis, IONM changes were associated with POD (odds ratio 2.12; 95% CI 1.31-3.44; p < 0.001). Additionally, baseline EEG abnormalities were associated with POD (p = 0.002). CONCLUSION: Significant IONM changes are associated with an increased risk of POD in patients undergoing cardiovascular surgery. These findings offer a basis for future research and analysis of EEG and somatosensory evoked potential monitoring to predict, detect, and prevent POD.

The Clinical Significance of Unplanned Coronary Artery Bypass Grafting in Aortic Root Replacement.

OBJECTIVES: Unexpected coronary artery bypass grafting (CABG) is occasionally required during aortic root replacement (ARR). However, the impact of unplanned CABG remains unknown. DESIGN: A single-center, retrospective observational study. SETTING: At university-affiliated tertiary hospital. PARTICIPANTS: All patients who underwent ARR from 2011 through 2022. INTERVENTIONS: Aortic root replacement with or without unplanned CABG. MEASUREMENTS AND MAIN RESULTS: A total of 795 patients underwent ARR. Among them, 131 (16.5%) underwent planned concomitant CABG, and 34 (4.3%) required unplanned CABG. The most common indication of unplanned CABG was ventricular dysfunction (33.3%), followed by disease pathology (25.6%), anatomy (15.4%), and surgical complications (10.3%). A vein graft to the right coronary artery was the most commonly performed bypass. Infective endocarditis and aortic dissection were observed in 27.8% and 12.8%, respectively. Prior cardiac surgery was seen in 40.3%. The median follow-up period was 4.3 years. Unplanned CABG was not associated with operative mortality (odds ratio [OR] 1.54, 95% CI 0.33-7.16, p = 0.58) or long-term mortality (hazard ratio 0.91, 95% CI 0.44-1.89, p = 0.81). Body surface area smaller than 1.7 was independently associated with an increased risk of unplanned CABG (OR 4.51, 95% CI 1.85-11.0, p < 0.001). CONCLUSIONS: Unplanned CABG occurred in 4.3% of patients during ARR, but was not associated with operative mortality or long-term mortality. A small body surface area was a factor associated with unplanned CABG.

Outcomes of Aortomitral Continuity Reconstruction During Concomitant Aortic and Mitral Valve Replacement.

OBJECTIVES: To describe outcomes of reconstruction of the aortomitral continuity (AMC) during concomitant aortic and mitral valve replacement (ie, the "Commando" procedure). DESIGN: A retrospective study of consecutive cardiac surgeries from 2010 to 2022. SETTING: At a single institution. PARTICIPANTS: All patients undergoing double aortic and mitral valve replacement. INTERVENTIONS: Patients were dichotomized by the performance (or not) of AMC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients underwent double-valve replacement, of whom 21 patients (6.3%) had a Commando procedure. The Commando group was more likely to have had a previous aortic valve replacement (AVR) or mitral valve replacement (MVR) (66.7% v 27.4%, p < 0.001), redo cardiac surgery (71.4% v 31.3%, p < 0.001), and emergent/salvage surgery (14.3% v 1.61%, p = 0.001), whereas surgery was more often performed for endocarditis in the Commando group (52.4% v 22.9%, p = 0.003). The Commando group had higher operative mortality (28.6% v 10.7%, p = 0.014), more prolonged ventilation (61.9% v 31.9%, p = 0.005), longer cardiopulmonary bypass time (312 ± 118 v 218 ± 85 minutes, p < 0.001), and longer ischemic time (252 ± 90 v 176 ± 66 minutes, p < 0.001). Despite increased short-term morbidity in the Commando group, Kaplan-Meier survival estimation showed no difference in long-term survival between each group (p = 0.386, log-rank). On multivariate Cox analysis, the Commando procedure was not associated with an increased hazard of death, compared to MVR + AVR (hazard ratio 1.29, 95% CI: 0.65-2.59, p = 0.496). CONCLUSIONS: Although short-term postoperative morbidity and mortality were found to be higher for patients undergoing the Commando procedure, AMC reconstruction may be equally durable in the long term.

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.

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.

Cost-benefit analysis of intraoperative neuromonitoring for cardiac surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) can detect large vessel occlusion (LVO) in real-time during surgery. The aim of this study was to conduct a cost-benefit analysis of utilizing IONM among patients undergoing cardiac surgery. METHODS: A decision-analysis tree with terminal Markov nodes was constructed to model functional outcome, as measured via the modified Rankin Scale (mRS), among 65-year-old patients undergoing cardiac surgery. Our cost-benefit analysis compares the use of IONM (electroencephalography and somatosensory evoked potential) against no IONM in preventing neurological complications from perioperative LVO during cardiac surgery. The study was performed over a lifetime horizon from a societal perspective in the United States. Base case and one-way probabilistic sensitivity analyses were performed. RESULTS: At a baseline LVO rate of 0.31%, the mean attributable lifetime expenditure for IONM-monitored cardiac surgeries relative to unmonitored cardiac surgeries was $1047.41 (95% CI, $742.12 - $1445.10). At a critical LVO rate of approximately 3.67%, the costs of both monitored and unmonitored cardiac surgeries were the same. Above this critical rate, implementing IONM became cost-saving. On one-way sensitivity analysis, variation in LVO rate from 0% - 10% caused lifetime costs attributable to receiving IONM to range from $1150.47 - $29404.61; variations in IONM cost, percentage of intervenable LVOs, IONM sensitivity, and mechanical thrombectomy cost exerted comparably minimal influence over lifetime costs. DISCUSSION: We find considerable cost savings favoring the use of IONM under certain parameters corresponding to high-risk patients. This study will provide financial perspective to policymakers, clinicians, and patients alike on the appropriate use of IONM during cardiac surgery.

Postoperative acute kidney injury after thoracic endovascular aortic repair for acute type B aortic dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has evolved as the standard for treating complicated acute type B aortic dissection (ATBAD). Acute kidney injury (AKI) is a common complication in critically ill patients and is commonly observed in patients with ATBAD. The purpose of the study was to characterize AKI after TEVAR. METHODS: All patients who underwent TEVAR for ATBAD from 2011 through 2021 were identified using the International Registry of Acute Aortic Dissection. The primary end point was AKI. A generalized linear model analysis was performed to identify a factor associated with postoperative AKI. RESULTS: A total of 630 patients presented with ATBAD and underwent TEVAR. The indication for TEVAR was complicated ATBAD in 64.3%, high-risk uncomplicated ATBAD in 27.6%, and uncomplicated ATBAD in 8.1%. Of 630 patients, 102 (16.2%) developed postoperative AKI (AKI group) and 528 patients (83.8%) did not (non-AKI group). The most common indication for TEVAR was malperfusion (37.5%). In-hospital mortality was significantly higher in the AKI group (18.6% vs 4%; P < .001). Postoperatively, cerebrovascular accident, spinal cord ischemia, limb ischemia, and prolonged ventilation were more commonly observed in the AKI group. The expected mortality was similar at 2 years between the two groups (P = .51). Overall, the preoperative AKI was observed in 95 (15.7%) in the entire cohort consisting of 60 (64.5%) in the AKI group and 35 (6.8%) in the non-AKI group. A history of CKD (odds ratio, 4.6; 95% confidence interval, 1.5-14.1; P = .01) and preoperative AKI (odds ratio, 24.1; 95% confidence interval, 10.6-55.0; P < .001) were independently associated with postoperative AKI. CONCLUSIONS: The incidence of postoperative AKI was 16.2% in patients undergoing TEVAR for ATBAD. Patients with postoperative AKI had a higher rate of in-hospital morbidities and mortality than those without. A history of CKD and preoperative AKI were independently associated with postoperative AKI.

Readmission with infective endocarditis within 90 days following transcatheter aortic valve implantation.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) continues to be the most common modality of treating aortic stenosis in the United States. While infective endocarditis (IE) and its outcomes have been well documented after surgical aortic valve replacement, the incidence and outcomes of early IE after TAVI have not been well described. METHODS: All patients who underwent TAVI from 2012 through 2018 were identified using the National Readmission Database. Among them, patients who underwent TAVI at the index admission and readmitted within 90 days were included. Patients who died or had IE during the index admission were excluded. Clinical outcomes were compared between patients readmitted with IE (IE group) and those without (non-IE group). RESULTS: A total of 168,283 patients were readmitted to a hospital within 90 days after TAVI. The median age of the IE group and non-IE group were 81 and 82 years old, respectively (p = 0.21). Of those, 525 (0.3%) were readmitted with IE. The median time from TAVI to readmission was 20 days. During readmissions, 11.6% of the IE group died while only 3.15% of the non-IE group experienced death (p < 0.001). The most common causative organism of IE was enterococcus (22.1%). Multivariable analysis revealed that congestive heart failure, cerebrovascular disease, dialysis, concomitant valve disease, Medicaid, and discharge to a facility were independently associated with readmission with IE within 90 days. CONCLUSION: The incidence of readmission with IE is low after TAVI. However, the mortality was markedly high during readmissions. Surgical intervention was rarely performed for IE during the first admission. Enterococcus was the most common organism observed in IE after TAVI. DISCLOSURE: IS receives institutional research support from Abbott, Atricure, cryolife, and Medtronic. None related to this manuscript. CLINICAL TRIAL REGISTRATION: Not applicable.

Midterm Outcomes of Endovascular vs. Medical Therapy for Uncomplicated Type B Aortic Dissection: Meta-Analysis of Reconstructed Time to Event Data.

OBJECTIVE: To evaluate outcomes of thoracic endovascular aortic repair (TEVAR) vs. medical therapy in uncomplicated type B aortic dissections (TBAD). DATA SOURCES: PubMed/MEDLINE, EMBASE, SciELO, LILACS, CENTRAL/CCTR, Google Scholar, and reference lists of relevant articles. REVIEW METHODS: This was a pooled meta-analysis of time to event data extracted from studies published by December 2022 for the following outcomes: all cause mortality, aortic related mortality, and late aortic interventions. Certainty of evidence was evaluated through the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. RESULTS: Ten studies met the eligibility criteria (eight observational; two randomised trials), comprising 17 906 patients (2 332 patients in the TEVAR groups and 15 574 patients in the medical therapy group). Compared with patients who received medical therapy, patients who underwent TEVAR had a statistically significantly lower risk of all cause death (HR 0.79, 95% CI 0.72 - 0.87, p < .001; GRADE certainty: low) and lower risk of aortic related death (HR 0.43, 95% CI 0.30 - 0.62, p < .001; GRADE certainty: low) without statistically significant difference in the risk of late aortic interventions (HR 1.05, 95% CI 0.88 - 1.26, p = .56; GRADE certainty: low). In the subgroup analyses, TEVAR was associated with lower risk of all cause death when randomised controlled trials only were pooled (HR 0.44, 95% CI 0.23 - 0.83, p = .012; GRADE certainty: moderate), younger patients only (HR 0.56, 95% CI 0.47 - 0.67, p < .001; GRADE certainty: low), Western populations only (HR 0.85, 95% CI 0.77 - 0.93, p = .001; GRADE certainty: low) and non-Western populations only (HR 0.47, 95% CI 0.35 - 0.62, p < .001; GRADE certainty: low). For all cause mortality and aortic related mortality, restricted mean survival time was overall 396 days and 398 days longer with TEVAR (p < .001), respectively, which means that TEVAR was associated with lifetime gain. CONCLUSION: TEVAR may be associated with better midterm survival and lower risk of aortic related death in the follow up of patients treated for uncomplicated TBAD compared with medical therapy; however, randomised controlled trials with larger sample sizes and longer follow up are still warranted.

The Long-Term Impact of Diastolic Dysfunction After Routine Cardiac Surgery.

OBJECTIVE: To determine the impact of diastolic dysfunction (DD) on survival after routine cardiac surgery. DESIGN: This was an observational study of consecutive cardiac surgeries from 2010 to 2021. SETTING: At a single institution. PARTICIPANTS: Patients undergoing isolated coronary, isolated valvular, and concomitant coronary and valvular surgery were included. Patients with a transthoracic echocardiogram (TTE) longer than 6 months prior to their index surgery were excluded from the analysis. INTERVENTIONS: Patients were categorized via preoperative TTE as having no DD, grade I DD, grade II DD, or grade III DD. MEASUREMENTS AND MAIN RESULTS: A total of 8,682 patients undergoing a coronary and/or valvular surgery were identified, of whom 4,375 (50.4%) had no DD, 3,034 (34.9%) had grade I DD, 1,066 (12.3%) had grade II DD, and 207 (2.4%) had grade III DD. The median (IQR) time of the TTE prior to the index surgery was 6 (2-29) days. Operative mortality was 5.8% in the grade III DD group v 2.4% for grade II DD, 1.9% for grade I DD, and 2.1% for no DD (p = 0.001). Atrial fibrillation, prolonged mechanical ventilation (>24 hours), acute kidney injury, any packed red blood cell transfusion, reexploration for bleeding, and length of stay were higher in the grade III DD group compared to the rest of the cohort. The median follow-up was 4.0 (IQR: 1.7-6.5) years. Kaplan-Meier survival estimates were lower in the grade III DD group than in the rest of the cohort. CONCLUSIONS: These findings suggested that DD may be associated with poor short-term and long-term outcomes.

A Novel Risk Score to Predict Thirty-Day Readmissions after Acute Type A Aortic Dissections.

BACKGROUND: Readmissions following acute type A aortic dissections (ATAAD) are associated with potentially worse clinical outcomes and increased hospital costs. Predicting which patients are at risk for readmission may guide patient management prior to discharge. METHODS: The National Readmissions Database was utilized to identify patients treated for ATAAD between 2010 and 2018. Univariate mixed effects logistic regression was used to assess each variable. Variables were assigned risk points based off the bootstrapped (bias-corrected) odds ratio of the final variable model according to the Johnson's scoring system. A mixed effect logistic regression was run on the risk score (sum of risk points) and 30-day readmission. Calibration plots and predicted readmission curves were generated for model assessment. RESULTS: A total of 30,727 type A aortic dissections were identified. The majority of ATAAD (66%) were in men with a median age of 61 years and 30-day readmission rate of 19.4%. The risk scores ranging from -1 to 14 mapped to readmission probabilities between 3.5% and 29% for ATAAD. The predictive model showed good calibration and receiver operator characteristics with an area under the curve (AUC) of 0.81. Being a resident of the hospital state (OR: 2.01 [1.64, 2.47], p < 0.001) was the highest contributor to readmissions followed by chronic kidney disease (1.35 [1.16, 1.56], p = 0), discharge to a short-term facility (1.31 [1.09, 1.57], p = 0.003), and developing a myocardial infarction (1.20 [1.00, 1.45], p = 0.048). CONCLUSIONS: The readmission model had good predictive capability given by the large AUC. Being a resident in the State of the index admission was the most significant contributor to readmission.

VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration.

BACKGROUND: Recent discoveries have indicated that, in the developing heart, sinus venosus and endocardium provide major sources of endothelium for coronary vessel growth that supports the expanding myocardium. Here we set out to study the origin of the coronary vessels that develop in response to vascular endothelial growth factor B (VEGF-B) in the heart and the effect of VEGF-B on recovery from myocardial infarction. METHODS: We used mice and rats expressing a VEGF-B transgene, VEGF-B-gene-deleted mice and rats, apelin-CreERT, and natriuretic peptide receptor 3-CreERT recombinase-mediated genetic cell lineage tracing and viral vector-mediated VEGF-B gene transfer in adult mice. Left anterior descending coronary vessel ligation was performed, and 5-ethynyl-2'-deoxyuridine-mediated proliferating cell cycle labeling; flow cytometry; histological, immunohistochemical, and biochemical methods; single-cell RNA sequencing and subsequent bioinformatic analysis; microcomputed tomography; and fluorescent- and tracer-mediated vascular perfusion imaging analyses were used to study the development and function of the VEGF-B-induced vessels in the heart. RESULTS: We show that cardiomyocyte overexpression of VEGF-B in mice and rats during development promotes the growth of novel vessels that originate directly from the cardiac ventricles and maintain connection with the coronary vessels in subendocardial myocardium. In adult mice, endothelial proliferation induced by VEGF-B gene transfer was located predominantly in the subendocardial coronary vessels. Furthermore, VEGF-B gene transduction before or concomitantly with ligation of the left anterior descending coronary artery promoted endocardium-derived vessel development into the myocardium and improved cardiac tissue remodeling and cardiac function. CONCLUSIONS: The myocardial VEGF-B transgene promotes the formation of endocardium-derived coronary vessels during development, endothelial proliferation in subendocardial myocardium in adult mice, and structural and functional rescue of cardiac tissue after myocardial infarction. VEGF-B could provide a new therapeutic strategy for cardiac neovascularization after coronary occlusion to rescue the most vulnerable myocardial tissue.

Hybrid and endovascular approaches to the aortic arch.

PURPOSE OF REVIEW: The gold standard treatment for aneurysms and dissections involving the aortic arch remains open total arch replacement. High-risk operative candidates may benefit from hybrid or completely endovascular techniques to reduce the risk of perioperative mortality and morbidity. RECENT FINDINGS: Numerous endografts are available for investigational use in the aortic arch as part of investigational device exemption (IDE) programs. Some are fenestrated or scalloped, whereas others are branched, ranging from single branch to triple branch stent-grafts. Initial results for completely endovascular repair of the aortic arch are encouraging. Current data estimates that rates of successful deployment of arch endografts ranges from 84.2% to 100%, whereas operative mortality may be as high as 13.2%, with stroke rates being as high as 20% and spinal cord ischemia being as high as 3.1%. SUMMARY: More data are necessary to compare hybrid and endovascular stent-grafting of the aortic arch to conventional open total arch replacement. Longitudinal follow-up is also lacking, which will determine the long-term durability of endografts in the aortic arch. However, endovascular repair represents an important opportunity for improving outcomes in high-risk patients with complex aneurysms and dissections of the aortic arch.

Revascularization Strategies for Multivessel Coronary Artery Disease in the Elderly Population.

BACKGROUND: Prospective trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for the treatment of multivessel coronary disease (MVCAD) have included mostly younger patients. We compared treatment strategies in the elderly population. MATERIALS AND METHODS: We performed a propensity-score-matched comparison of patients ≥75 y who underwent isolated CABG or PCI for MVCAD between 2011 and 2018, excluding those with prior cardiac surgery and/or significant left main disease. The primary outcome was 5-year Kaplan Meier survival, and secondary outcomes included readmissions and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Propensity-matching yielded 536 patients (266 PCI and 266 CABG). Rates of complete revascularization of all stenotic lesions were higher in the CABG arm (86.8% versus 21.8%; P < 0.001). Thirty-d mortality was similar between cohorts, though PCI recipients had shorter hospital stay and greater likelihood of discharge to home. Unadjusted one- (89.1% versus 88.4%) and 5-year (73.8% versus 60.1%) survival were both higher in patients who underwent CABG (P = 0.0332). Patients undergoing CABG had reduced, but nonsignificant cumulative incidence of all-cause hospital readmission and MACCE at 5 y. Subgroup analysis of patients 80 y or older revealed similar late survival benefit with CABG when compared to PCI. Among patients undergoing CABG, there did not appear to be any 5-year benefits from multi-arterial grafting. CONCLUSIONS: Despite longer hospitalization and higher rate of nonhome discharge, CABG was associated with improved late survival over PCI in the elderly population. Cardiac surgeons should be included in the multidisciplinary evaluation of older patients with MVCAD.

Midterm Outcomes of Isolated Coronary Artery Bypass Grafting in the Setting of Moderate Ischemic Mitral Regurgitation.

INTRODUCTION: Although randomized trial data exist for 2-y outcomes comparing isolated coronary artery bypass grafting (CABG) versus CABG with concomitant mitral valve repair (CABG + MVr) for the treatment of moderate ischemic mitral regurgitation (IMR), longer term outcomes are unclear. This study evaluated the longitudinal outcomes of isolated CABG for moderate IMR. METHODS: Patients with moderate IMR undergoing isolated CABG from January 2010 to February 2018 at a single institution were included. Outcomes included longitudinal freedom from heart failure readmission, survival, rates of persistent mitral regurgitation (MR), and freedom from mitral valve reinterventions. A subanalysis was conducted comparing CABG versus CABG + MVr. Multivariable Cox regression was used for risk adjustment. RESULTS: A total of 528 patients with moderate IMR underwent isolated CABG. Postoperatively, 26% of patients had at least moderate MR at 1-mo follow-up, although at 5 y progression to severe MR was rare (2.2%) as were mitral valve reinterventions (0.2%). Survival at 30 d (95.8%), 1 y (89.6%), and 5 y (76.6%) was acceptable. Furthermore, the freedom from readmission for heart failure was also acceptable at 30 d (92.6%), 1 y (79.9%), and 5 y (65.0%) postoperatively. In a subanalysis comparing CABG versus CABG + MVr, unadjusted and risk-adjusted survival, freedom from heart failure readmissions, mitral valve reinterventions, and degrees of MR were comparable between the groups at all intervals (all P > 0.05). CONCLUSIONS: The majority of patients with moderate IMR can undergo isolated CABG with acceptable rates of heart failure readmissions, survival, progression to severe MR, and the need for subsequent mitral interventions. These data support the use of isolated CABG in patients with moderate IMR.