Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Heart Transplantation in Adriamycin-Associated Cardiomyopathy in the Contemporary Era of Advanced Heart Failure Therapies.

BACKGROUND: Adriamycin-associated cardiomyopathy (ACM) can lead to end-stage heart failure requiring advanced heart failure therapies. OBJECTIVES: This study sought to provide post-cardiac transplant survival data in patients with ACM in the contemporary era of mechanical circulatory support and cardiac transplantation. METHODS: Adults (≥18 years of age) who underwent first-time, single-organ heart transplantation were identified from the United Network for Organ Sharing between October 18, 2008, and October 18, 2018. Cardiomyopathy subtypes that could have been supported with a left ventricular assist device (LVAD) including ACM, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM) were included. A multivariable Cox regression analysis was performed to determine the association between cardiomyopathy subtype and post-cardiac transplant survival. RESULTS: This analysis included 18,270 patients (357 with ACM; 10,662 with DCM; and 7,251 with ICM). Heart transplant recipients with ACM were younger, included more women, and had higher pulmonary vascular resistance at the time of listing. Patients with ACM had a lower percentage of durable LVADs at the time of transplant across all years of the study period. Patients with ACM did not experience an increase in post-cardiac transplant mortality compared to those with DCM (adjusted hazard ratio: 0.96; 95% confidence interval: 0.79 to 1.40; p = 0.764) or ICM (adjusted hazard ratio: 0.85; 95% confidence interval: 0.6 to 1.2; p = 0.304). CONCLUSIONS: Patients with ACM who received heart transplants between 2008 and 2018 had similar post-cardiac transplant survival to those with dilated and ischemic cardiomyopathy. Bridge-to-transplant LVAD use remains lower compared to other cardiomyopathy subtypes.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. METHODS: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. RESULTS: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups. CONCLUSIONS: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

Association of Left Atrial Enlargement and Atrial Fibrillation With Cognitive Function and Decline: The ARIC-NCS.

Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2-dimensional echocardiograms at visit 5 (2011-2013) and follow-up cognitive tests at visit 6 (2016-2017). LAE was defined as left atrium volume index ≥34 mL/m2. AF was ascertained using study ECGs and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF, normal left atrium), participants with LAE and AF had significantly lower global cognition (Z score, -0.24; 95% CI, -0.38 to -0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition (Z score, -0.13; 95% CI, -0.21 to -0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross-sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow-up and evaluate left atrium function.

Impact of 30 Day Readmission After Left Ventricular Assist Device Implantation.

Early readmission (within 30 days) after left ventricular assist device (LVAD) implantation might be a marker for increased mortality. We retrospectively reviewed the records of 277 adults who underwent continuous-flow LVAD implantation from 2005 through 2015 at our institution. The baseline characteristics of patients who were (versus were not) readmitted within 30 days after LVAD implantation were compared. To assess the impact of 30 day readmission on long-term survival, we used multivariate Cox regression. We also compared the cardiac transplant rate between the two groups. Of the 277 patients, 217 (78.3%) underwent LVAD implantation as a bridge-to-transplant; 76 (27.4%) of the 277 were readmitted within 30 days. The most common reason for readmission was volume overload (23.6%), followed by gastrointestinal bleeding (15.8%). Male gender, previous smoking, a higher baseline creatinine level, higher Model for End Stage Liver Disease Excluding INR (MELD-XI) score, and postoperative gastrointestinal bleeding or stroke were each associated with 30 day readmission. In our final multivariate model, increased mortality was also associated with 30 day readmission (hazard ratio, 1.60; 95% confidence interval, 1.1-2.5). Among the 217 bridge-to-transplant patients, the cardiac transplant rate was similar between the two groups: 18.7 transplants per patient-year among those who were readmitted within 30 days versus 19.7 transplants per patient-year among those who were not (p = 0.26). Among our study patients, 30 day readmission after LVAD implantation was frequent and was associated with increased mortality. It is currently unclear whether the general health of those patients was a factor and whether efforts to reduce 30 day readmission would favorably affect longer-term patient outcomes.

Impact of Postoperative Liver Dysfunction on Survival After Left Ventricular Assist Device Implantation.

BACKGROUND: Liver dysfunction in left ventricular assist device (LVAD) recipients is common both before and after implantation. Postoperative liver dysfunction (PLD) develops in some LVAD recipients without preoperative liver dysfunction. The aim of this study was to assess clinical outcomes in such patients. METHODS: Records of all patients undergoing implantation of a HeartMate II (HM II, St. Jude Medical, Inc, Minneapolis, MN) LVAD at a single center at the University of Minnesota from January 2005 through June 2014 were analyzed. PLD was defined by hypertransaminasemia or hyperbilirubinemia, or both, during the hospitalization for LVAD implantation. RESULTS: During the study period, 284 patients underwent HM II implantation. Excluded from analysis were 14 recipients with preoperative liver dysfunction. In the final cohort (n = 270), there were no major difference in preoperative characteristics among those patients with versus without PLD. PLD developed in 129 (47.8%) recipients: 16 (12.4%) had isolated hypertransaminasemia (group I), 76 (58.9%) had isolated hyperbilirubinemia (group II), and 37 (28.7%) had combined hypertransaminasemia and hyperbilirubinemia (group III). Group III LVAD recipients had significantly greater rates of 30-day, 90-day, and 1-year mortality, along with significantly higher transfusion requirements and higher rates of renal replacement therapy, prolonged ventilation, and vasopressor use. Moreover, their mortality risk was significantly higher than that of PLD-free LVAD recipients (hazard ratio, 4.6; 95% confidence interval, 2.1 to 10.1; p < 0.001). CONCLUSIONS: Isolated hyperbilirubinemia is common after LVAD implantation. In this study, it was not associated with an increase in early or midterm postoperative mortality. However, postoperative combined transaminasemia and hyperbilirubinemia was associated with a significant increase in early and midterm morbidity and mortality. Further research into the pathogenesis of post-LVAD PLD is necessary.

High prevalence of subclinical cerebral infarction in patients with heart failure with preserved ejection fraction.

AIMS: Undetected atrial fibrillation (AF) may be common in the heart failure with preserved ejection fraction (HFpEF) population, and failure to detect this may lead to the missing of opportunities to prevent associated subclinical cerebral infarctions (SCIs) and cognitive decline. METHODS AND RESULTS: We studied 1527 participants in the Atherosclerosis Risk in Communities (ARIC) Study, who underwent echocardiography, brain magnetic resonance imaging (MRI) and detailed cognitive assessment during 2011-13. Prevalences of SCI as detected by brain MRI were compared among the following groups: participants with no HFpEF/no AF; those with no HFpEF/AF; those with HFpEF/no AF, and those with HFpEF/AF. Cognitive scores were also compared. Prevalences of HFpEF and AF in this sample were 13.2% and 5.7%, respectively. Participants with HFpEF but no prior diagnosis of AF had a high prevalence of SCI by brain MRI (29.3%), which was similar to those in the no HFpEF/AF (24.5%) and HFpEF/AF (23.5%) groups, but higher than that in the no HFpEF/no AF subjects (17.3%). The odds of having SCI were higher in participants with HFpEF/no AF than in the no HFpEF/no AF group even after adjustment for potential confounders (odds ratio 1.56, 95% confidence interval 1.06-2.30). Individuals with HFpEF and SCI had lower cognitive scores than the reference (no HFpEF/no SCI) and HFpEF/no SCI groups. CONCLUSIONS: Subclinical cerebral infarctions were prevalent in subjects in the ARIC cohort with HFpEF and no prior AF diagnosis and are associated with measurable cognitive deficits. Although other sources of emboli may be possible, these data suggest that paroxysmal AF may be underdiagnosed in this population. There may be a role for earlier anticoagulation in patients with HFpEF.