Deo, Salil V.

Background: Concerns exist regarding orthotropic heart transplantation (OHT) in hepatitis C (HCV) seropositive recipients. The UNOS national registry was accessed to evaluate HCV recipient sero-positivity and outcomes. Method: Retrospective analysis of the UNOS registry (2000-2014) to evaluate recipient profile and clinical outcome of HCV sero-positive (HCV+ve) and sero-negative (HCV -ve) pts. Early and late adjusted survival and adverse events at follow-up were compared. Results: From 23,507 patients (mean age 52 yrs; 75% male), 481 (2%) were HCV +ve (mean age 52 yrs; 77% male). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3-2.7%; p=0.2). The HCV +ve cohort had more African American (22% vs 17%; p=0.01), pts with a prior LVAD (21 vs 14%; p<0.01 and more hepatitis B core Ag+ve recipients (17% vs 5%; p<0.01). However, ECMO (p=0.7), inotropic (p=0.2), and intra-aortic balloon pump (p=0.7) support, serum creatinine (p=0.7) and serum bilirubin (p=0.7) were similar. Proportion of Status 1A pts was similar (24% HCV+ vs 21% HCV -); however wait-time for HCV + recipients was longer (mean 23 vs 19 days; p<0.01). Among donor variables, age (p=0.8), hepatitis B status (p=0.4) and CDC high risk status (p=0.9) were comparable. At a median follow up of 4 years, 67.1% patients were alive, 28.4% died and 1.1% were re-transplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3 vs 72.9 % and 43.2 vs 55% at five and ten years; p<0.01). Late renal [OR 1.2(1-1.6); p = 0.02] and liver dysfunction [OR 4.5 (1.2-15.7); p=0.01] occur in HCV +ve recipients. On adjusted analysis, HCV sero-positivity is associated with poorer survival [HR0.6 (0.5-0.8); p<0.01]. Conclusion: A small proportion of patients receiving a heart transplant in the United States have hepatitis C. In spite of comparable pre-operative hepatic function, hepatitis C sero-positive recipients develop late liver dysfunction and have poorer long-term survival.

Introduction: Limited data is available regarding the incidence of new-onset diabetes mellitus (NODM) after heart transplantation and it`s impact on patient survival. Hypothesis: Methods: From the United Network of Organ Sharing database (January 2004 to September 2014), we identified 13,353 patients without pre-operative diabetes mellitus undergoing heart transplantation. Multivariable Cox regression was implemented to determine predictors for the development of NODM. A matched cohort of New-onset Diabetes mellitus (NODM (+)) and NODM (-) was generated by 1:1 nearest neighbor propensity-matching. The association of NODM with long-term survival was then estimated with robust Cox regression. Results are presented at the 95% Confidence level; all tests are two-tailed. Results: During the study period, 1,921 of 13,353 (14%) developed NODM. Estimated freedom from NODM was 97% (96-98%) & 77% (76 - 78%) at the end of 1 and 5 years respectively. Predictors for the development of NODM were recipient age > 50 years (HR 1.2 95% CI1.05, 1.3; p < 0.01), recipient BMI > 30 (HR 1.4 95% CI1.2, 1.6; p < 0.01) and race (African American vs Caucasian (HR 1.3 95% CI1.2, 1.5; p < 0.01)). Cox-regression of a propensity-matched cohort of 1921 NODM+ve and NODM-ve recipient-pairs demonstrates that NODM is associated with poorer survival (HR for mortality: 1.3 95% CI 1.1, 1.5; p < 0.001). Conclusions: More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival. More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival.

Background Although cardiovascular mortality (CVM) rates in the United States have been declining overall, our study evaluated whether this holds true for areas with increased social deprivation. Methods and Results We used county‐level cross‐sectional age‐adjusted CVM rates (aa‐CVM) (2000–2019) linked to the Centers for Disease Control and Prevention Social Vulnerability Index (SVI–2010). We grouped counties as per SVI (Groups I 0–0.2, II 0.21–0.4, III 0.41–0.6, IV 0.61–0.8, and V 0.81–1) and calculated the relative change in the aa‐CVM between 2000 to 2003 and 2016 to 2019. We used adjusted linear regression analyses to explore the association between a higher SVI and temporal aa‐CVM improvement; we studied this temporal change in aa‐CVM across subgroups of race, sex, and location. The median aa‐CVM rate (per 100 000) was 272.6 (interquartile range [IQR]: 237.5–311.7). The aa‐CVM was higher in men (315.6 [IQR: 273.4–363.9]) than women (221.3 [IQR: 189.6–256.7]), and in Black residents (347.2 [IQR: 301.1–391.1]; P <0.001) than White residents (258.9 [IQR: 226–299.1]; P <0.001). The aa‐CVM for SVI I (233.6 [IQR: 214.8–257.0]) was significantly lower than that of group V (323.6 [IQR: 277.2–359.2]; P <0.001). The relative reduction in CVM was significantly higher for SVI group I (32.2% [IQR: 24.2–38.4]) than group V (27.2% [IQR: 19–34.1]) counties. After multivariable adjustment, a higher SVI index was associated with lower relative improvement in the age‐adjusted CVM (model coefficient −3.11 [95% CI, −5.66 to −1.22]; P <0.001). Conclusions Socially deprived counties in the United States had higher aa‐CVM rates, and the improvement in aa‐CVM over the past 20 years was lower in these counties.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background: Effective lipid lowering therapy reduces deaths due to atherosclerotic vascular disease (ASCVD). Proprotein convertase subtilsin/kexin type 9 inhibitor (PCSK9i) drugs have emerged as effective add-on therapy to lower low-density lipoprotein (LDL) levels. Although the use of PCSK9i is limited by cost, PCSK9i use in a low-cost healthcare system [Veteran Health Affairs (VHA)] is unknown. Methods: We queried a cohort of US Veterans with coronary artery disease (CAD), PAD or CeVD receiving outpatient care (January 2016 – December 2019) at 124 VHA medical centers to evaluate the initiation of PCSK9i. We fit a mixed effects logistic regression model [with results presented as odds ratio (OR)] to evaluate the association of social deprivation (assessed by median household income and community deprivation index), the patient’s primary diagnosis and VHA medical center enrollment with PCSK9i initiation. Findings: From 519,566 patients (median age 74 years), 337,766 (65%), 79,926 (15%) and 101,874 (20%) had CAD, PAD and CeVD. Among 2,115/519,566 (0.4%) initiated with PCSK9i therapy, 84.3% had CAD, while only 7.2% and 8.5% had PAD and CeVD respectively. PCSK9i initiation was lower in those earning $40,000 - $80,000 [OR 1.13 (1.01 – 1.27)] or > $80,000 [OR 1.41 (1.14 – 1.75)]. Even moderate community deprivation [OR 0.87 (0.77 – 0.97)] was associated with lower PCSK9i therapy. Compared to CAD patients, PAD [OR 0.50 (0.35 – 0.70)] and CeVD [OR 0.23 (0.15 – 0.37)] were less likely to receive PCSK9i. Interpretation: Despite low co-pay, PCSK9i initiation rates among US veterans, nationwide, is very low. PAD and CeVD patients are much less likely to receive PCSK9i therapy. Household income and community deprivation influence PCSK9i use.

Background Coronary artery bypass can be performed off pump (OPCAB) without cardiopulmonary bypass. However, trends over time for OPCAB versus on‐pump (ONCAB) use and long‐term outcome has not been reported, nor has their long‐term outcome been compared. Methods and Results We queried the national Veterans Affairs database (2005–2019) to identify isolated coronary artery bypass procedures. Procedures were classified as OPCAB on ONCAB using the as‐treated basis. Trend analyses were performed to evaluate longitudinal changes in the preference for OPCAB. The median follow‐up period was 6.6 (3.5–10) years. An inverse probability weighted Cox model was used to compare all‐cause mortality between OPCAB and ONCAB. From 47 685 patients, 6759 (age 64±8 years) received OPCAB (14%). OPCAB usage declined from 16% (2005–2009) to 8% (2015–2019). Patients with triple vessel disease who received OPCAB received a lower mean number of grafts (2.8±0.8 versus 3.2±0.8; P <0.01). The ONCAB 5‐, 10‐, and 15‐year survival rates were 82.9% (82.5–83.3), 60.4% (59.8–61.1), and 37.2% (36.1–38.4); correspondingly, OPCAB rates were 80.7% (79.7–81.7), 57.4% (56–58.7), and 34.1% (31.7–36.6) ( P <0.01). OPCAB was associated with increased risk‐adjusted all‐cause mortality (hazard ratio, 1.15 [1.13–1.18]; P <0.01) and myocardial infarction (incident rate ratio, 1.16 [1.05–1.28]; P <0.01). Conclusions Over 15 years, OPCAB use declined considerably in Veterans Affairs medical centers. In Veterans Affairs hospitals, late all‐cause mortality and myocardial infarction rates were higher in the OPCAB cohort.

Aims Despite the common occurrence of coronary artery disease (CAD) and heart failure (HF) with preserved ejection fraction (HFpEF), there is limited evidence to guide revascularization. Methods and Results We investigated the long‐term outcomes of coronary artery bypass grafting (CABG) in patients with HF and significant CAD across the spectrum of ejection fraction, using a large national cohort of patients from the Veteran Affairs (VA) Medical Centers in the US. Patients with HF were stratified into groups, HFpEF, HF with mid‐range ejection fraction (HFmrEF), and HF with reduced ejection fraction (HFrEF) and compared to patients with no preoperative HF. We analysed 10 396 patients. Despite an increased hazard in the first year following revascularization, the long‐term survival (median follow‐up 6.6 years; interquartile range 3.7–10.1) of HFpEF post‐CABG was similar to controls (hazard ratio 0.85, 95% confidence interval 0.68‐1.06), but survival progressively declined with HFmrEF and HFrEF. Similar trends were seen with recurrent HF hospitalization with lower risk with baseline HFpEF (43.9 ± 6.9/100 patient‐years) compared to HFmrEF (65.9 ± 3.8/100 patient‐years) and HFrEF (93.4 ± 4.8/100 patient‐years). Although HFpEF patients had lower mortality and HF hospitalization post‐CABG compared to patients with a lower ejection fraction, they experienced the highest rates of future myocardial infarction. Conclusion Although HFpEF patients with CAD have greater short‐term risk post‐CABG, their long‐term survival is comparable to controls. However, they are at increased risk for HF hospitalizations and myocardial infarction. These data support the safety of CABG in HFpEF patients and suggest continuum of mortality risk for ischaemic HF when stratified by baseline ejection fraction before revascularization.

Abstract OBJECTIVES This study sought to evaluate the long-term differences in survival between multiple arterial grafts (MAG) and single arterial grafts (SAG) in patients who underwent coronary artery bypass grafting (CABG) in the SYNTAX study. METHODS The present analysis included the randomized and registry-treated CABG patients (n = 1509) from the SYNTAX Extended Survival study (SYNTAXES). Patients with only venous (n = 42) or synthetic grafts (n = 1) were excluded. The primary end point was all-cause death at the longest follow-up. Multivariable Cox regression was used to adjust for differences in baseline characteristics. Sensitivity analysis using propensity matching with inverse probability for treatment weights was performed. RESULTS Of the 1466 included patients, 465 (31.7%) received MAG and 1001 (68.3%) SAG. Patients receiving MAG were younger and at lower risk. At the longest follow-up of 12.6 years, all-cause death occurred in 23.6% of MAG and 40.0% of SAG patients [adjusted hazard ratio (HR) 0.74, 95% confidence interval (CI) (0.55–0.98); P = 0.038], which was confirmed by sensitivity analysis. MAG in patients with the three-vessel disease was associated with significant lower unadjusted and adjusted all-cause death at 12.6 years [adjusted HR 0.65, 95% CI (0.44–0.97); P = 0.033]. In contrast, no significance was observed after risk adjustment in patients with the left main disease, with and without diabetes, or among SYNTAX score tertiles. CONCLUSIONS In the present post hoc analysis of all-comers patients from the SYNTAX trial, MAG resulted in markedly lower all-cause death at 12.6-year follow-up compared to a SAG strategy. Hence, this striking long-term survival benefit of MAG over SAG encourages more extensive use of multiple arterial grafting in selected patients with reasonable life expectancy. Trial registration SYNTAXES ClinicalTrials.gov reference: NCT03417050; SYNTAX ClinicalTrials.gov reference: NCT00114972.