Chantal ElAmm

Model for end-stage liver disease excluding international normalized ratio (MELD-XI) score predicts heart transplant outcomes: Evidence from the registry of the United Network for Organ Sharing

BACKGROUND Hepato-renal function is a valuable predictor of success after left ventricular assist device therapy and heart transplantation. Hence, we analyzed the importance of the Model for End-stage Liver Disease excluding international normalized ratio (MELD-XI) score to outcomes after heart transplant. METHODS Adults undergoing heart transplant from the United Network for Organ Sharing (UNOS) database were identified (1994 to 2014). Individual MELD-XI scores were calculated; patients were stratified by MELD-XI quartiles (Q1 to Q4). Multivariate logistic regression and the Cox proportional hazard model were implemented to determine any association between MELD-XI scores, survival and other outcomes. RESULTS From 39,711 patients undergoing OHT during the study period, MELD-XI score [median 10.7 (interquartile range 7.0 to 14.4)] was calculated for 36,005 patients (76% male and 75% white, 34% Status 1A). Higher MELD-XI scores had higher rates of pre-transplant extracorporeal membrane oxygenation, intra-aortic balloon pump, inotrope use and mechanical ventilation (p < 0.001 for all). Adjusted long-term mortality (median follow-up 8.1 years) was associated with MELD-XI score (hazard ratio [HR] 1.021 [1.016 to 1.026], p < 0.001). The highest MELD-XI quartile was associated with an HR 1.364 [1.255 to 1.482] risk of mortality compared with Q1. MELD-XI score was also associated with increased post-transplant infections (adjusted HR Q4 vs Q1: 1.364 [1.153 to 1.614], p < 0.001), stroke (adjusted HR Q4 vs Q1: 1.410 [1.074 to 1.852], p = 0.013), dialysis (adjusted HR Q4 vs Q1: 3.982 [3.386 to 4.683], p < 0.001), rejection (adjusted HR Q4 vs Q1: 1.519 [1.286 to 1.795], p = 0.003) and prolonged hospitalization (adjusted HR Q4 vs Q1: 1.635 [1.429 to 1.871], p < 0.001). CONCLUSION Hepato-renal dysfunction, measured with MELD-XI score, predicts morbidity and mortality in patients undergoing orthotopic heart transplantation. Etiology of hepato-renal dysfunction should be sought and treated before heart transplantation.

Left Ventricular Assist Devices or Inotropes for Decreasing Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension Listed for Heart Transplantation

BACKGROUND Fixed pulmonary hypertension is common in patients with advanced heart failure and is a contraindication for heart transplantation. Left ventricular assist devices (LVAD) and inotropes have been used to reduce pulmonary vascular resistance (PVR) and allow transplantation. However, little is known about the efficacy of this strategy. METHODS We queried the United Network for Organ Sharing registry for all adult patients (age ≥18 years) listed for primary heart transplantation (2008-2014) with PVR of >5 wood units (WU) or transpulmonary gradient >16 mmHg who were treated with LVAD or IV inotropes as status 1a, 1b, or 7. We compared waitlist mortality/delisting and absolute changes in hemodynamics between listing and transplantation. RESULTS Of 18,009 patients listed during the study period, 1016 were included in the analysis (393 LVAD, 623 inotropes), with a mean age of 52.9 ± 11.6 years, 74% male, and 38% had ischemic etiology. Mean PVR was 5.7 ± 2.4 WU and transpulmonary pressure gradient 19.3 ± 5.3 mmHg. Compared with the inotrope group, LVAD patients were more likely listed as status 1A (32.8% vs 18.1%, P < .001), had lower PVR (5.3 WU vs 5.9 WU, P = .001), and higher cardiac output (4.1 vs 3.6 L/min, P < .001). After a mean of 239 days, PVR decreased by 1.71 WU in the LVAD group vs 1.85 WU in the inotrope group (P = .52). PVR normalization (<2.5 WU) occurred at similar rates among those treated with inotropes and LVAD (30.7% vs 35.6%, P = .228). Waitlist mortality was similar between LVAD and inotropes (adjusted P = .837). Absolute PVR and transpulmonary pressure gradient reductions correlated with time on the waitlist (P < .001 for both comparisons). CONCLUSION Only about one-third of patients with fixed pulmonary hypertension achieve normalization of PVR before transplant with either LVAD or inotropes. Similar waitlist mortality was observed among patients bridged with either strategy.

Heart failure in patients with human immunodeficiency virus infection: Epidemiology and management disparities.

BACKGROUND Persons living with HIV are at a higher risk of cardiovascular disease despite effective antiretroviral therapy and dramatic reductions in AIDS-related conditions. We sought to identify the epidemiology of heart failure (HF) among persons living with HIV in the United States in an era of contemporary antiretroviral therapy. METHODS Explorys is an electronic healthcare database that aggregates medical records from 23 healthcare systems nationwide. Using systemized nomenclature of medicine-clinical terms (SNOMED-CT), we identified adult patients (age>18), who had active records over the past year (September 2014-September 2015). We described the prevalence of HF in HIV patients by demographics and treatment and compared them to HIV-uninfected controls. RESULTS Overall, there were 36,400 patients with HIV and 12,208,430 controls. The overall prevalence of HF was 7.2% in HIV and 4.4% in controls (RR 1.66 [1.60-1.72], p<0.0001). The relative risk of HF associated with HIV infection was higher among women and younger age groups. Patients receiving antiretroviral therapy had only marginally lower risk (6.4% vs. 7.7%, p<0.0001) of HF compared to those who were untreated. Compared to uninfected patients with HF, HIV patients with HF were less likely to receive antiplatelet drugs, statins, diuretics, and ACE/ARBs (p<0.0001 for all comparisons). For patients with HIV and HF, receiving care from a cardiologist was associated with higher use of antiplatelets, statins, betablockers, ACE/ARBs, and diuretics. CONCLUSIONS Persons with HIV are at higher risk for HF in this large contemporary sample that includes both men and women. Although the prevalence of heart failure is higher in older HIV patients, the relative risk associated with HIV is highest in young people and in women. HIV patients are less likely to have HF optimally treated, but cardiology referral was associated with higher treatment rates.

Heart transplant outcomes in patients with left ventricular non-compaction cardiomyopathy.

BACKGROUND Left ventricular non-compaction cardiomyopathy (LVNCC) is a rare disease that starts in utero and may progress to heart failure (HF), sometimes requiring orthotopic heart transplantation (OHT). There are limited data addressing characteristics of LVNCC patients that require OHT and their outcomes. We therefore sought to investigate the characteristics and outcomes of LVNCC patients treated with OHT. METHODS We queried the United Network for Organ Sharing (UNOS) database for all patients listed for OHT with LVNCC as the primary heart failure etiology between 2000 and 2013. We examined their characteristics at listing and outcomes after OHT and compared the findings with those of patients with idiopathic cardiomyopathy (IDCMP). RESULTS We identified 113 patients (43 adults and 70 pediatrics) with LVNCC of 45,298 patients (0.25% overall, 0.11% of adults and 1.0% of pediatrics) listed for OHT in this time period. Most were male children with mean age at listing of 16.9 years. Compared with the overall IDCMP cohort, patients with LVNCC were younger, had higher use of inotropes and extracorporeal membrane oxygenation (ECMO), and were more often listed as UNOS Status 1A with shorter waiting time. However, when adjusted for age, gender and ethnicity, these differences disappeared. During transplant listing, 8 (7.9%) died, 5 (5.0%) improved and avoided transplant, 3 (3.0%) became too sick for transplant and 78 (77.2%) underwent OHT. There was a non-significant trend toward longer cardiac allograft survival in patients with LVNCC (10.6 vs. 9.4 years; log-rank test, p = 0.068). Patients with LVNCC had similar outcomes to other IDCMP patients, except for more post-transplant infections (50.0% vs. 21.6%, p < 0.05). CONCLUSIONS LVNCC patients undergoing heart transplantation are mostly pediatric and predominantly bridged to transplant with inotropes or ECMO. Despite having more post-transplant infections, their survival is similar to that of other IDCMP patients.

Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma

Purpose: To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping. Experimental Design: In a multicenter prospective study of 90 patients with mRCC, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These “on-drug” visits corresponded to cycles 1, 3, and 6, respectively. Left ventricular (LV) dysfunction was defined as an absolute decline in LV ejection fraction (LVEF) by ≥10% to a value of <50%. Conditional survival analyses predicted the risk of LV dysfunction. Linear mixed-effects models estimated changes in LVEF, high-sensitivity Troponin I (hsTnI), and B-type natriuretic peptide (BNP) over time. Results: The predicted risk of LV dysfunction by cycle 6 was 9.7% (95% confidence interval, 3%–17%). The majority of events occurred in the first treatment cycle. This risk diminished to 5% and 2% in patients who had not experienced dysfunction by the completion of cycles 1 and 3, respectively. All evaluable patients who experienced LV dysfunction had subsequent improvement in LVEF with careful management. Six patients (6.7%) developed hsTnI elevations >21.5 pg/mL, and 11 additional patients (12.2%) developed BNP elevations >100 pg/mL. These elevations similarly tended to occur early and resolved over time. Conclusions: On average, patients with mRCC receiving sunitinib exhibit modest declines in LVEF and nonsignificant changes in hsTnI and BNP. However, approximately 9.7% to 18.9% of patients develop more substantive abnormalities. These changes occur early and are largely recoverable with careful management. Clin Cancer Res; 23(14); 3601–9. ©2017 AACR.

Reversal of Severe Biventricular Dysfunction From Cardiac Hemochromatosis With Iron Removal

A 47-year-old man presented with 1-week history of cough and bilateral lower extremity swelling. He had a 5-year history of diabetes mellitus and hypogonadism. His ECG demonstrated sinus rhythm with low-limb voltage and left anterior hemiblock. An echocardiogram showed severely reduced left ventricular ejection fraction 10%, restrictive diastolic filling, and severe right ventricular dysfunction (Figure 1, Movie I–IV in the online-only Data Supplement). Laboratory testing revealed brain natriuretic peptide 1849 pg/mL, ferritin 6389 µg/L, iron 108 µg/dL, transferrin 124 mg/dL, total iron binding capacity 171 µg/dL, and transferrin saturation 63%. Figure 1. Echocardiogram showed early:atrial mitral inflow velocity ratio (E/A) >2, short deceleration time (DT) …

Platelet Inhibition With Ticagrelor for Left Ventricular Assist Device Thrombosis

Although considered standard therapy for Stage D heart failure since 2008, the continuous, axial flow HeartMate II (HMII) left ventricular assist device (LVAD) has recently been associated with unexpected rise in rates of pump thrombosis.1 With an incidence of 0.01 to 0.11 events per patient-year, LVAD thrombosis responds to intensification of antithrombotic therapy with unfractionated heparin (UFH), dual antiplatelet therapy with or without thrombolytics or glycoprotein IIb/IIIa inhibition in <50% of cases, and is associated with nearly 50% 6-month mortality.1 Therefore, surgical pump exchange or urgent transplantation remains the treatment of choice despite potential high risk and cost. Herein, we report the first successful experience using the potent P2Y12 ADP receptor inhibitor ticagrelor in addition to UFH and aspirin (acetylsalicylic acid [ASA]) to treat LVAD thrombosis and avoid pump exchange in 4 patients with confirmed or suspected HMII thrombosis. With institutional Instituitional Review Board approval, we reviewed medical records of 4 consecutive patients admitted to the cardiac intensive care unit at our institution with confirmed or suspected LVAD thrombosis. LVAD thrombosis was diagnosed in the presence of abrupt elevations of serum lactate dehydrogenase (LDH) to >900 mg/dL without (suspected LVAD thrombosis) or with (confirmed LVAD thrombosis) 1 of the following: (1) abnormal LVAD flows or power surges, (2) clinical symptoms of heart failure, or (3) supporting echocardiographic ramp study. We determined antiplatelet activity using VerifyNow P2Y12 assay, with values >230 P2Y12 reaction units (PRU) indicating nonresponder status. Patients were treated clinically using standard doses of medications based on clinical preference. ### Patient 1 A 28-year-old black man had HMII implanted as destination therapy for nonischemic cardiomyopathy before 7 days. Postsurgical course was complicated by slowly increasing LDH with peak of 980 U/L, requiring maintenance of UFH in addition to ASA 325 mg daily, dipyridamole, later switched to clopidogrel. Because LDH remained …

Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network for Organ Sharing Registry

BACKGROUND Giant cell myocarditis (GCM) is a lethal, rapidly progressive disease, for which heart transplantation is the treatment of choice. We sought to describe the characteristics and outcomes of patients with GCM who undergo heart transplantation. METHODS AND RESULTS We used the United Network for Organ Sharing thoracic organ transplantation registry to identify adults with GCM as the primary diagnosis and compared their characteristics and outcomes with patients who underwent transplantation for other types of myocarditis and for idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were compared with 219 patients with myocarditis and 14,221 patients with IDCMP. Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the majority were white (94%), male (63%), and listed as 1A (44%). Biventricular assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P < .001). After transplantation, there were no statistically significant differences among GCM, myocarditis, and IDCMP patients regarding pacemaker implantation, dialysis initiation, or stroke rate. GCM patients had increased risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but no difference in rehospitalization for rejection among the 3 etiologies (P = .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%, 82%, and 68%, respectively, which was similar to the other etiologies (P = .11). CONCLUSIONS Compared with patients with IDCMP, those with GCM present more acutely and have significantly higher utilization of biventricular mechanical circulatory support. Despite higher rates of early rejection, post-transplantation survival of patients with GCM was similar to that of other myocarditides and IDCMP.

First-in-Human Experience With Transcatheter Mitral Valve-in-Valve Implantation During Left Ventricular Assist Device Placement

Valvular disease is common in patients undergoing left ventricular assist device (LVAD) implantation. Concomitant valve surgery increases procedural complexity and cardiopulmonary bypass time and may lead to worse outcomes.1 Although mitral regurgitation is the most common mitral valve dysfunction in patients undergoing LVAD implantation, mitral stenosis (MS) is occasionally encountered. MS can lead to restricted LVAD flow; therefore, mitral valve replacement is considered to be reasonable in patients with hemodynamically significant MS undergoing LVAD implantation. We describe a successful transcatheter mitral valve replacement (TMVR) via a transapical approach with concomitant LVAD implantation in a patient with bioprosthetic MS. Our patient is a 67-year-old male with ischemic cardiomyopathy, stage D heart failure with reduced ejection fraction, and left ventricular ejection fraction 15%. He had prior 6-vessel coronary artery bypass grafting, bioprosthetic mitral valve replacement (Medtronic Mosaic porcine mitral valve, 29-mm size) for severe mitral regurgitation, and a modified endoventricular circular patch plasty (Dor procedure) for left ventricular aneurysm repair. He had cardiac resynchronization therapy and defibrillator therapy and was paced 99% but remained symptomatic with low output symptoms, as confirmed by hemodynamic assessment. By the time of referral to our institution, he had been hospitalized multiple times in the preceding 6 months with acutely decompensated heart failure, severe ascites, and malnutrition and was maintained on home inotropic therapy with Milrinone at …

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Background: Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. Methods and Results: In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e′), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0–17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3–10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid–femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. Conclusions: In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.