Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

Cystatin C- Versus Creatinine-Based Assessment of Renal Function and Prediction of Early Outcomes Among Patients With a Left Ventricular Assist Device.

BACKGROUND: Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies. METHODS: A prospective cohort (n=116) with CysC and sCr concurrently measured at serial time points, and a retrospective cohort (n=91) with chest computed tomography performed within 40 days post-LVAD were studied. In the prospective cohort, the primary end point was a composite of in-hospital mortality, renal replacement therapy, or severe right ventricular failure. In the retrospective cohort, muscle mass was estimated using pectoralis muscle area indexed to body surface area (pectoralis muscle index). RESULTS: In the prospective cohort, sCr-eGFR significantly improved early post-LVAD and subsequently declined, whereas CysC-eGFR remained stable. CysC-eGFR but not sCr-eGFR predicted the primary end point: odds ratio per 5 mL/(min·1.73 m2) decrease 1.16 (1.02-1.31) versus 0.99 (0.94-1.05). In retrospective cohort, for every 5 days post-LVAD, a 6% decrease in pectoralis muscle index was observed (95% CI, 2%-9%, P=0.003). After adjusting for time on LVAD, for every 1 cm2/m2 decrease in pectoralis muscle index, there was a 4% decrease in 30-day post-LVAD sCr (95% CI, 1%-6%, P=0.004). CONCLUSIONS: Initial improvement in sCr-eGFR is likely due to muscle wasting following LVAD surgery. CysC may improve assessment of renal function and prediction of early postoperative outcomes in patients with an LVAD.

Socioeconomic Disparities in Adherence and Outcomes After Heart Transplant: A UNOS (United Network for Organ Sharing) Registry Analysis.

BACKGROUND: There is mixed evidence of racial and socioeconomic disparities in heart transplant outcomes. Their underlying cause-and whether individual- or community-level traits are most influential-remains unclear. The current study aimed to characterize socioeconomic disparities in outcomes and identify time trends and mediators of these disparities. METHODS AND RESULTS: We used United Network for Organ Sharing registry data and included 33 893 adult heart transplant recipients between 1994 and 2014. Socioeconomic status (SES) indicators included insurance, education, and neighborhood SES measured using a composite index. Black race and multiple indicators of low SES were associated with the primary outcome of death or retransplant, independent of baseline clinical characteristics. Blacks had lower HLA and race matching, but further adjustment for these and other graft characteristics only slightly attenuated the association with black race (HR, 1.25 after adjustment). This and the associations with neighborhood SES (HR, 1.19 for lowest versus highest decile), Medicare (HR, 1.17), Medicaid (HR, 1.29), and college education (HR, 0.90) remained significant after full adjustment. When comparing early (1994-2000) and late (2001-2014) cohorts, the disparities associated with the middle (second and third) quartiles significantly decreased over time, but those associated with lowest SES quartile and black race persisted. Low neighborhood SES was also associated with higher risks of noncompliance (HR, 1.76), rejection (HR, 1.28), hospitalization (HR, 1.13), and infection (HR, 1.10). CONCLUSIONS: Racial and socioeconomic disparities exist in heart transplant outcomes, but the latter may be narrowing over time. These disparities are not explained by differences in clinical or graft characteristics.

Limited usefulness of endoscopic evaluation in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients. METHODS: We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation. RESULTS: Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%. CONCLUSIONS: Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization.

Impact of Socioeconomic Status on Patients Supported With a Left Ventricular Assist Device: An Analysis of the UNOS Database (United Network for Organ Sharing).

BACKGROUND: Low socioeconomic status (SES) is a known risk factor for heart failure, mortality among those with heart failure, and poor post heart transplant (HT) outcomes. This study sought to determine whether SES is associated with decreased waitlist survival while on left ventricular assist device (LVADs) support and after HT. METHODS AND RESULTS: A total of 3361 adult patients bridged to primary HT with an LVAD between May 2004 and April 2014 were identified in the UNOS database (United Network for Organ Sharing). SES was measured using the Agency for Healthcare Research and Quality SES index using data from the 2014 American Community Survey. In the study cohort, SES did not have an association with the combined end point of death or delisting on LVAD support (P=0.30). In a cause-specific unadjusted model, those in the top (hazard ratio, 1.55; 95% confidence interval, 1.14-2.11; P=0.005) and second greatest SES quartile (hazard ratio 1.50; 95% confidence interval, 1.10-2.04; P=0.01) had an increased risk of death on device support compared with the lowest SES quartile. Adjusting for clinical risk factors mitigated the increased risk. There was no association between SES and complications. Post-HT survival, both crude and adjusted, was decreased for patients in the lowest quartile of SES index compared with all other SES quartiles. CONCLUSIONS: Freedom from waitlist death or delisting was not affected by SES. Patients with a higher SES had an increased unadjusted risk of waitlist mortality during LVAD support, which was mitigated by adjusting for increased comorbid conditions. Low SES was associated with worse post-HT outcomes. Further study is needed to confirm and understand a differential effect of SES on post-transplant outcomes that was not seen during LVAD support before HT.

Clinical indication for use and outcomes after inhaled nitric oxide therapy.

BACKGROUND: Inhaled nitric oxide (iNO) use is widespread, but the long-term outcomes after therapy in adult patients remain unknown. METHODS: All 376 patients receiving perioperative iNO (excluding pediatric and interventional cardiology procedures) at Columbia University Medical Center were prospectively followed from 2000 to 2003. Survival data were collected from chart review. RESULTS: Inhaled nitric oxide was used to treat pulmonary and right ventricular failure in patients undergoing orthotopic heart transplantation (OHT, n = 67), orthotopic lung transplantation (n = 45), cardiac surgery (n = 105), and ventricular assist device placement (n = 66), and for hypoxemia in other surgery (n = 34) and medical patients (n = 59). Average follow-up was 2.9 +/- 1.0 years. Overall mortality was lowest when iNO was used after OHT (25.4%) and orthotopic lung transplantation (37.8%), intermediately after cardiac surgery (61%), ventricular assist device (62%), and other surgery patients (75%), and highest among medical patients (90%; all p < 0.005). The cost of iNO therapy was lower in transplantation versus medical patients, with a trend toward shorter duration of use. In multivariate analysis, respiratory failure and use in non-OHT were independent predictors of mortality (both p = 0.001). A risk score greater than 1 (score = non-OHT use 1, plus right ventricular failure 1) predicted a mortality of 76.5% versus 37.2% (p < 0.001). CONCLUSIONS: Use of iNO for pulmonary hypertension in patients undergoing OHT and orthotopic lung transplantation was associated with a significantly lower overall mortality rate compared with its use after cardiac surgery or for hypoxemia in medical patients. Inhaled nitric oxide does not appear to be cost effective when treating hypoxemia in medical patients with high-risk scores and irreversible disease.