QT prolongation predicts all-cause mortality above and beyond a validated risk score.

INTRODUCTION: QT prolongation is a risk factor for life-threatening arrhythmias and sudden cardiac death. In large cohorts, QT interval was associated with all-cause mortality, but these analyses may contain residual confounding. Whether the QT interval provides prognostic information above and beyond a validated mortality risk score is unknown. We hypothesized that QT interval on ECG will independently predict mortality after adjustment for the Care Assessment Needs (CAN) score, which was validated to predict mortality nationwide at the Veterans Administration (VA) (c-index 0.86). METHODS: Outpatients with an ECG at the Minneapolis VA from 2012 to 2016 were included in this retrospective cohort study. ECGs with ventricular rate < 50 or > 100 beats/min and those with QRS > 120 ms were excluded. QT intervals were corrected (QTc) using the Bazett's formula. CAN score, calculated within 1-week of the ECG, was obtained from the VA Corporate Data Warehouse. RESULTS: Of the 31,201 patients, 427 (1.4%) had QTc ≥ 500 ms, 1799 (5.8%) had QTc 470-500 ms and 28,975 (92.9%) had QTc < 470 ms. Compared to those with QTc < 470 ms, CAN-adjusted odds ratios (OR) for 1-year mortality (1.76 for QTc 470-500 and 2.70 for QTc > 500 ms; p < 0.0001 for both) and for 5-year mortality (1.75 for QTc 470-500 and 2.48 for QTc > 500 ms; p < 0.0001 for both) were significantly higher in those with longer QTc. C-index for CAN score and QTc predicting 1-year mortality was 0.837. CONCLUSIONS: QT prolongation predicts all-cause mortality independently of a validated mortality risk prediction score.

Perioperative changes in left ventricular systolic function following surgical revascularization.

BACKGROUND: Nearly 1/3rd of patients undergoing coronary artery bypass graft surgery (CABG) have left ventricular systolic dysfunction. However, the extent, direction and implications of perioperative changes in left ventricular ejection fraction (LVEF) have not been well characterized in these patients. METHODS: We studied the changes in LVEF among 549 patients with left ventricular systolic dysfunction (LVEF <50%) who underwent CABG as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Patients had pre- and post-CABG (4 month) LVEF assessments using identical cardiac imaging modality, interpreted at a core laboratory. An absolute change of >10% in LVEF was considered clinically significant. RESULTS: Of the 549 patients (mean age 61.4±9.55 years, and 72 [13.1%] women), 145 (26.4%) had a >10% improvement in LVEF, 369 (67.2%) had no change and 35 (6.4%) had >10% worsening of LVEF following CABG. Patients with lower preoperative LVEF were more likely to experience an improvement after CABG (odds ratio 1.36; 95% CI 1.21-1.53; per 5% lower preoperative LVEF; p <0.001). Notably, incidence of postoperative improvement in LVEF was not influenced by presence, nor absence, of myocardial viability (25.5% vs. 28.3% respectively, p = 0.67). After adjusting for age, sex, baseline LVEF, and NYHA Class, a >10% improvement in LVEF after CABG was associated with a 57% lower risk of all-cause mortality (HR: 0.43, 95% CI: 0.26-0.71). CONCLUSIONS: Among patients with ischemic cardiomyopathy undergoing CABG, 26.4% had >10% improvement in LVEF. An improvement in LVEF was more likely in patients with lower preoperative LVEF and was associated with improved long-term survival.

Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator.

INTRODUCTION: Left ventricular ejection fraction (EF) ≤ 35% is the cornerstone criterion for implantable cardioverter-defibrillator (ICD) eligibility. Improvement in EF may occur in ICD-eligible patients after coronary artery bypass graft surgery (CABG). However, the incidence, predictors, and outcomes of this process are unclear. METHODS AND RESULTS: We studied 427 patients with EF ≤ 35% who underwent CABG in the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had a systematic pre- and postoperative (4 months) EF assessment using the identical cardiac imaging modality. All imaging studies were interpreted at a core laboratory. Improvement in EF was defined as postoperative EF > 35% and >5% absolute improvement from baseline. Of the 427 patients (mean age 61.8 ± 9.5 and 50 women), 125 (29.2%) had EF improvement. Their mean EF increased from 26.8% (±5.8%) to 43.3% (±6.5%) (p < .0001). EF improvement occurred in only 20% of patients with a preoperative EF < 25%. The odds of EF improvement were 1.96 times higher (95% confidence interval [CI]: 0.91-4.23, p = .09) in patients with myocardial viability. In adjusted analyses, EF improvement was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR]: 0.58, 95% CI: 0.35-0.96; p = .03) and heart failure mortality (HR: 0.31, 95% CI: 0.11-0.87; p = .027). CONCLUSION: Nearly 1/3rd of ICD-eligible patients undergoing CABG had significant improvement in EF, obviating the need for primary prevention ICD implantation. These results provide patients and clinicians data on the likelihood of ICD eligibility after CABG and support the practice of reassessment of EF after revascularization.

Effect of systemic heparan sulfate haploinsufficiency on steady state hematopoiesis and engraftment of hematopoietic stem cells.

Heparan sulfate (HS) proteoglycans on stromal and hematopoietic stem/progenitor cells (HSPC) help form the stem cell niche, co-localize molecules that direct stem cell fate, and modulate HSPC homing and retention. Inhibition of HS function mobilizes marrow HSPC. In vitro, HSPC maintenance is influenced by stromal HS structure and concentration. Because inhibition of HS activity or synthesis may be developed for HSPC transplantation, it is important to examine if systemic HS deficiency influences hematopoiesis in vivo. In a transgenic mouse model of HS haploinsufficiency, we examined endogenous hematopoiesis and engraftment of allogeneic bone marrow. Endogenous hematopoiesis was normal except gender-specific alterations in peripheral blood monocyte and platelet counts. Donor engraftment was achieved in all mice following myeloablative irradiation, but HS deficiency in the stromal microenvironment, on HSPC, or both (the 3 test conditions), was associated with a trend towards lower donor engraftment percentage in the bone marrow. Following non-myeloablative irradiation, competitive engraftment was achieved in 22% of mice in the test conditions, vs 50% of control animals (P = 0.03). HS deficiency did not re-direct donor engraftment from bone marrow to spleen or liver. Normal HS levels in the stromal microenvironment and HSPC are required for HSPC engraftment following non-myeloablative conditioning.