Long-term results of surgical ventricular reconstruction and comparison with the Surgical Treatment for Ischemic Heart Failure trial.

OBJECTIVE: The role of surgical ventricular reconstruction (SVR) in patients with ischemic cardiomyopathy is controversial. Observational series and the Surgical Treatment of IsChemic Heart failure (STICH) trial reported contradictory results. SVR is highly dependent on operator experience. The aim of this study is to compare the long-term results of SVR between a high-volume SVR institution and the STICH trial using individual patient data. METHODS: Patients undergoing SVR at San Donato Hospital (Milan) were compared with patients undergoing SVR in STICH (as-treated principle) by inverse probability treatment-weighted Cox regression. The primary outcome was all-cause mortality. RESULTS: The San Donato cohort included 725 patients, whereas the STICH cohort included 501. Compared with the STICH-SVR cohort, San Donato patients were older (66.0, lower quartile, upper quartile [Q1, Q3: 58.0, 72.0] vs 61.9 [Q1, Q3: 55.1, 68.8], P < .001) and with lower left ventricular end-systolic volume index at baseline (LVESVI: 77.0 [Q1, Q3: 59.0, 97.0] vs 80.8 [Q1, Q3: 58.5, 106.8], P = .02). Propensity score weighting yielded 2 similar cohorts. At 4-year follow-up, mortality was significantly lower in the San Donato cohort compared with the STICH-SVR cohort (adjusted hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .001). Greater postoperative LVESVI was independently associated with mortality (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03). At 4 to 6 months of follow-up, the mean reduction of LVESVI in the San Donato cohort was 39.6%, versus 10.7% in the STICH-SVR cohort (P < .001). CONCLUSIONS: Patients with postinfarction LV remodeling undergoing SVR at a high-volume SVR institution had better long-term results than those reported in the STICH trial, suggesting that a new trial testing the SVR hypothesis may be warranted.

Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

BACKGROUND: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results. METHODS: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. RESULTS: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations. CONCLUSIONS: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00023595.

Restoring ventricular restoration: A call to re-evaluate a surgical therapy considered ineffective.

The technique of surgical restoration of postischemically dilated left ventricles (SVR) has almost disappeared from operating theaters after the Surgical Treatment of IsChemic Heart failure (STICH) Trial demonstrated no treatment effect in patients with CAD and ejection fraction below 35%. Criticism on the trial was expressed stating that surgical expertise and patient selection (i.e., almost no aneurysm patients included) may have been inadequate to test the procedure s potential. Gaudino and colleagues now propose to conduct an analysis comparing the STICH patient population to a group of comparable SVR patients treated by a center with documented specific expertise for this technique. We here address the background of the trial and the following controversy and suggest a rationale why the suggested analysis has the potential to add valuable information to the field.

De Novo Renal Failure and Clinical Outcomes of Patients With Critical Coronavirus Disease 2019.

OBJECTIVES: To describe the characteristics and outcomes associated with concomitant renal and respiratory failure in patients with critical coronavirus disease 2019. DESIGN, SETTING, AND PATIENTS: This is a case series of patients from a U.S. healthcare system in New York City. All adult patients (≥ 18 yr) admitted to the hospital with positive coronavirus disease 2019 testing between March 10, 2020, and March 31, 2020, who required mechanical ventilatory support were included. Patients who remained hospitalized were followed through May 1, 2020. INTERVENTIONS: Renal replacement therapy included at least one session of dialysis, continued venovenous hemofiltration, or peritoneal dialysis. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, laboratory markers, 30-day in-hospital outcomes, ventilator days, and survival to discharge were included. Multivariate predictors for mortality and need for renal replacement therapy were identified. A total of 330 patients were included in this analysis and were most commonly greater than or equal to 70 years (40%), male (61%), Black or African American (41%), and Hispanic or Latino (38%). Renal replacement therapy was required in 101 patients (29%), most commonly among Blacks or African Americans (50%). Elevated d-dimer, C-reactive protein, and procalcitonin were associated with renal replacement therapy, compared with the nondialysis cohort. Overall, 243 patients (74%) died and 56 (17%) were discharged from the hospital, of which 9 (3%) required renal replacement therapy. Male sex (odds ratio, 2.0; 1.1-3.5; p = 0.020), Black race (odds ratio, 1.8; 1.0-3.1; p = 0.453), and history of hypertension (odds ratio, 2.7; 1.3-5.4; p = 0.005) were predictors for requiring renal replacement therapy. Risk factors for in-hospital mortality included age greater than or equal to 60 years (odds ratio, 6.2; 3.0-13.0; p < 0.0001), male sex (odds ratio, 3.0; 1.4-6.4; p = 0.004), and body mass index greater than or equal to 30 kg/m2 (odds ratio, 2.1; 1.0-4.4; p = 0.039). Concomitant renal failure in critical coronavirus disease 2019 was not a significant predictor of death (odds ratio, 2.3; 0.98-5.5; p = 0.057). CONCLUSIONS: This case series concludes that respiratory failure conveys significant mortality risk in patients with coronavirus disease 2019 and that survival with concomitant renal failure is rare.

Cost-effectiveness of coronary artery bypass grafting plus mitral valve repair versus coronary artery bypass grafting alone for moderate ischemic mitral regurgitation.

OBJECTIVE: The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. METHODS: We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. RESULTS: In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. CONCLUSIONS: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Aortic recoarctation and pseudoaneurysm five decades after repair.

BACKGROUND: Coarctation of the aorta is a congenital cardiac defect characterized by a narrowing of the proximal thoracic aorta. Despite excellent long-term results, surgical repair is rarely complicated by recoarctation. METHODS/RESULTS: We describe a case with the longest time to reintervention to date, featuring surgical repair of delayed aortic recoarctation and pseudoaneurysm 53 years after the initial operation. DISCUSSION: This case emphasizes the need for lifelong surveillance in this patient population and exemplifies a multidisciplinary approach in evaluating treatment options of complex aortic pathology, including open and endovascular considerations.

Does prior coronary angioplasty affect outcomes of surgical coronary revascularization? Insights from the STICH trial.

BACKGROUND: The STICH trial showed superiority of coronary artery bypass plus medical treatment (CABG) over medical treatment alone (MED) in patients with left ventricular ejection fraction (LVEF) ≤35%. In previous publications, percutaneous coronary intervention (PCI) prior to CABG was associated with worse prognosis. OBJECTIVES: The main purpose of this study was to analyse if prior PCI influenced outcomes in STICH. METHODS AND RESULTS: Patients in the STICH trial (n = 1212), followed for a median time of 9.8 years, were included in the present analyses. In the total population, 156 had a prior PCI (74 and 82, respectively, in the MED and CABG groups). In those with vs. without prior PCI, the adjusted hazard-ratios (aHRs) were 0.92 (95% CI = 0.74-1.15) for all-cause mortality, 0.85 (95% CI = 0.64-1.11) for CV mortality, and 1.43 (95% CI = 1.15-1.77) for CV hospitalization. In the group randomized to CABG without prior PCI, the aHRs were 0.82 (95% CI = 0.70-0.95) for all-cause mortality, 0.75 (95% CI = 0.62-0.90) for CV mortality and 0.67 (95% CI = 0.56-0.80) for CV hospitalization. In the group randomized to CABG with prior PCI, the aHRs were 0.76 (95% CI = 0.50-1.15) for all-cause mortality, 0.81 (95% CI = 0.49-1.36) for CV mortality and 0.61 (95% CI = 0.41-0.90) for CV hospitalization. There was no evidence of interaction between randomized treatment and prior PCI for any endpoint (all adjusted p > 0.05). CONCLUSION: In the STICH trial, prior PCI did not affect the outcomes of patients whether they were treated medically or surgically, and the superiority of CABG over MED remained unchanged regardless of prior PCI. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT00023595.

Differential Impact of Mitral Valve Repair on Outcome of Coronary Artery Bypass Grafting With or Without Surgical Ventricular Reconstruction in the Surgical Treatment for Ischemic Heart Failure (STICH) Trial.

BACKGROUND: This study examined the impact of mitral valve repair (MVRe) on survival of patients with moderate or severe (≥2+) MR and ischemic cardiomyopathy randomized to coronary artery bypass grafting (CABG) versus CABG+surgical ventricular reconstruction (SVR) in the STICH trial. METHODS: Among patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG or CABG+SVR, the impact of MVRe on mortality between the two treatment arms was compared. RESULTS: Among 867 patients with assessment of baseline MR severity, 211 had moderate or severe MR. After excluding 7 patients who underwent mitral valve replacement, 50, 44, 62, and 48 patients underwent CABG, CABG+MVRe, CABG+SVR, and CABG+SVR+MVRe, respectively. Four-year mortality rates were lower following CABG+MVRe than CABG alone (16% vs. 55%; adjusted hazard ratio [HR] 0.30; 95% CI 0.13-0.71). In contrast, the CABG+SVR+MVRe and CABG+SVR groups had similar 4-year mortality of 39% vs. 39% (adjusted HR 0.88; 95% CI 0.46-1.70). MVRe had a more favorable effect on survival in patients undergoing CABG alone compared to CABG+SVR (p=0.013). Baseline MR severity was similar between patients that received CABG+MVRe and those that underwent CABG+SVR+MVRe. A larger proportion of patients demonstrated a reduction in MR between 4 and 24 months after CABG+MVRe compared to CABG+SVR+MVRe (50.0% versus 25.0%, p=0.023). CONCLUSION: In patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG, MVRe appears to have a favorable effect on survival. The addition of SVR to CABG may attenuate the anticipated benefits of MVRe by limiting the long-term reduction of MR with MVRe.

Prospective US investigational device exemption trial of a sutureless aortic bioprosthesis: One-year outcomes.

OBJECTIVES: We performed a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption to assess safety and efficacy of Perceval, a sutureless bovine pericardial aortic valve representing the initial US experience. METHODS: From June 2013 to January 2015, 300 patients (mean age 76.7 ± 7.7 years, 54.3% men, 37.3% ≥80 years, median Society of Thoracic Surgeons Predicted Risk of Mortality 2.8%), underwent Perceval valve implantation at 18 centers across the United States. Twenty patients (6.7%) had a bicuspid aortic valve and 5 (1.7%) patients had previous aortic valve replacement. A minimally invasive approach was used in 80 (26.7%) and concomitant procedures were performed in 113 (37.8%) patients. RESULTS: Two hundred eighty-nine patients (96.3%) were successfully implanted. Operative mortality (≤30 days) was 1.3% (n = 4) (observed to expected ratio of 0.40). One-year results included all-cause mortality in 5.2% (n = 15), stroke in 1% (n = 3), and endocarditis in 1.7% (n = 5). New permanent periprocedural pacemaker rate was 10.7% (n = 30/281); 2.5% (n = 7/281) resulted from third-degree atrioventricular block. One-year valve-related reoperation was 2.1% (n = 6). At 1-year follow-up, 98% of patients were in New York Heart Association class I/II, left ventricular mass index decreased from 103.5 ± 30.1 g/m2 at discharge to 95.8 ± 27.1 g/m2 (P = .001), and 3 (1.3%) moderate paravalvular leaks were identified. Health-related quality of life score increased from 62.7 ± 21.8 before surgery to 85.5 ± 17.8 at 1 year (P < .001). CONCLUSIONS: These results confirm the safety and effectiveness of the Perceval sutureless aortic valve replacement in study patients with lower mortality than expected from a risk prediction model. Persistent hemodynamic benefit and improvement in quality of life at 1 year support the importance of this device in the management of aortic valve disease.

Society of Thoracic Surgeons Risk Score and EuroSCORE-2 Appropriately Assess 30-Day Postoperative Mortality in the STICH Trial and a Contemporary Cohort of Patients With Left Ventricular Dysfunction Undergoing Surgical Revascularization.

BACKGROUND: The STICH trial (Surgical Treatment for Ischemic Heart Failure) demonstrated a survival benefit of coronary artery bypass grafting in patients with ischemic cardiomyopathy and left ventricular dysfunction. The Society of Thoracic Surgeons (STS) risk score and the EuroSCORE-2 (ES2) are used for risk assessment in cardiac surgery, with little information available about their accuracy in patients with left ventricular dysfunction. We assessed the ability of the STS score and ES2 to evaluate 30-day postoperative mortality risk in STICH and a contemporary cohort (CC) of patients with a left ventricle ejection fraction ≤35% undergoing coronary artery bypass grafting outside of a trial setting. METHODS AND RESULTS: The STS and ES2 scores were calculated for 814 STICH patients and 1246 consecutive patients in a CC. There were marked variations in 30-day postoperative mortality risk from 1 patient to another. The STS scores consistently calculated lower risk scores than ES2 (1.5 versus 2.9 for the CC and 0.9 versus 2.4 for the STICH cohort), and underestimated postoperative mortality risk. The STS and ES2 scores had moderately good C statistics: CC (0.727, 95% CI: 0.650-0.803 for STS, and 0.707, 95% CI: 0.620-0.795 for ES2); STICH (0.744, 95% CI: 0.677-0.812, for STS and 0.736, 95% CI: 0.665-0.808 for ES2). Despite the CC patients having higher STS and ES2 scores than STICH patients, mortality (3.5%) was lower than that of STICH (4.8%), suggesting a possible decrease in postoperative mortality over the past decade. CONCLUSIONS: The 30-day postoperative mortality risk of coronary artery bypass grafting in patients with left ventricular dysfunction varies markedly. Both the STS and ES2 score are effective in evaluating risk, although the STS score tend to underestimate risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

The current status of stem cell therapy in ischemic heart disease.

The last decade has witnessed the publication of a number of stem cell clinical trials, primarily using bone marrow-derived cells as the injected cell. Much has been learned through these "first-generation" clinical trials. The advances in our understanding include (1) cell therapy is safe; (2) cell therapy has been mildly effective; and (3) human bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels. The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines; chemokines; and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate regenerative mechanisms through endogenous circulating or site-specific stem cells. The current direction for clinical trials includes the use of stem cells capable of cardiac lineage.

Impact of Intubation Time on Survival following Coronary Artery Bypass Grafting: Insights from the Surgical Treatment for Ischemic Heart Failure (STICH) Trial.

OBJECTIVE: The authors aimed to assess determinants of intubation time and evaluate its impact on 30-day and 1-year postoperative survival in Surgical Treatment for Ischemic Heart Failure (STICH) trial patients. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A multivariable Cox proportional hazards model was used among the 1,446 surgical patients from the STICH trial who survived 36 hours after operation, in order to identify perioperative factors associated with 30-day and 1-year postoperative mortality. A multivariable logistic regression model was used to determine risk factors associated with intubation time. MEASUREMENTS AND MAIN RESULTS: At 36 hours post-operation, 1,298 (out of 1,446) were extubated and 148 (10.2%) still intubated. Median postoperative intubation time was 11.4 hours. Among patients surviving 36 hours, a multivariable model was developed to predict 30-day (c-index = 0.88) and 1-year (c-index = 0.78) mortality. Intubation time was the strongest independent predictor of 30-day (hazard ratio [HR] 5.50) and 1-year mortality (HR 3.69). Predictors of intubation time >36 hours included mitral valve procedure, New York Heart Association class, left ventricular systolic volume index, creatinine, previous coronary artery bypass grafting (CABG), and age. Results were similar in patients surviving 24 hours post-operation, where intubation time was also the strongest predictor of 30-day (HR 4.18, c-index 0.87) and 1-year (HR 2.81, c-index 0.78) mortality. CONCLUSIONS: Intubation time is the strongest predictor of 30-day and 1-year mortality among patients with ischemic heart failure undergoing CABG. Combining intubation time with other mortality risk factors may allow the identification of patients at the highest risk for whom the development of specific strategies may improve outcomes.

A Comparison of Inflammatory Responses Between Robotically Enhanced Coronary Artery Bypass Grafting and Conventional Coronary Artery Bypass Grafting: Implications for Hybrid Revascularization.

OBJECTIVE: The inflammatory response elicited by robotically enhanced coronary artery bypass grafting (r-CABG) has not been well described. When r-CABG is performed as part of hybrid coronary revascularization, the inflammatory milieu and the timing of percutaneous coronary intervention may affect the stent patency negatively in the short and long term. The goal of this study was to describe the extent and time course of cytokine release after r-CABG compared with conventional CABG (c-CABG) and to elucidate the optimal timing for r-CABG in the setting of hybrid coronary revascularization for a future study. DESIGN: Prospective, observational study. SETTING: Tertiary-care center in a university hospital. PARTICIPANTS: The study comprised patients scheduled to undergo r-CABG or c-CABG from October 2012 to November 2014. INTERVENTIONS: Cytokine levels of interleukin (IL)-6, IL-8, IL-10; tumor necrosis factor-α; and C-reactive protein (CRP) were measured at the following time points: preprocedure; at the end of the procedure; and at 4, 8, 12, 24, and 48 hours after the procedure. MEASUREMENTS AND MAIN RESULTS: Twenty-eight patients undergoing r-CABG and 10 patients undergoing c-CABG were enrolled. The levels of cytokines after r-CABG and c-CABG were compared using the mixed-effect linear regression model for longitudinal data. Cytokine release in the r-CABG group was comparatively less for IL-6, IL-10, tumor necrosis factor, and CRP levels. They all trended toward the baseline by the 48th hour in both groups, except CRP levels, which reached their peak at 48 hours in both groups. CONCLUSIONS: The inflammatory response to r-CABG was blunted compared with that of c-CABG. The high CRP levels on the second postoperative day after r-CABG were a cause for concern in regard to percutaneous coronary intervention performed at that time period, but additional studies are necessary.