Mahazarin Ginwalla

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.

2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair Jesse E. Adams III, MD, FACC James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC John E. Brush Jr, MD, FACC Lori Daniels, MD, MAS, FACC Susan Fernandes, LPD, PA-C Rosario Freeman, MD, MS,

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 …

2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients with Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently, …

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 …

Successful use of palliative inotrope therapy in end-stage cardiac ATTR amyloidosis

Patients with heart failure (HF) due to senile (wild type, wt) transthyretin amyloidosis have an overall poor prognosis and are not usually candidates for advanced therapies including heart transplantation (HT) or left ventricular assist devices (LVAD). In these patients, the use of inotropic therapy has not been studied. In this case report, we describe the successful use of chronic palliative inotrope therapy using home milrinone in a patient with end-stage ATTRwt amyloidosis for over two years. Our patient is a 77-year-old man who was newly diagnosed in February of 2014 with atrial fibrillation and heart failure with left ventricular ejection fraction (EF) 20–25% at the time of diagnosis. A nuclear stress test was negative for ischaemia. Cardiac magnetic resonance imaging (MRI) showed diffuse dilatation of all four chambers with myocardial enhancement in a non-coronary pattern highly suggestive of an infiltrative process. Endomyocardial biopsy was consistent with amyloid deposition. Genetic testing revealed age-related senile1 wild-type transthyretin amyloidosis (ATTRwt). He was initially managed medically with metoprolol for rate control of his atrial fibrillation and furosemide. An angiotensin-converting enzyme inhibitor was not used due to his chronic renal disease and fluctuating renal function. He remained in New York Heart Association (NYHA) Class II HF. However, he progressively declined and was admitted a year after initial diagnosis with cardiogenic shock. He was initiated on intravenous milrinone for inotropic support, titrated to 0.25mcg/kg/min. Milrinone was selected over dobutamine due to its longer half-life, and its attribute of increasing the heart rate to a lower extent as compared to dobutamine [1]. The patient was also cardioverted successfully; however, he reverted back to atrial fibrillation soon after. He was initiated on amiodarone; however, he developed bradycardia and it was discontinued along with his beta blocker. Given his age and advanced amyloidosis, he was deemed not to be a candidate for a HT or LVAD. He was discharged home on continuous palliative home milrinone at 0.25mcg/kg/min. He was started on hydralazine and isosorbide mononitrate. An implantable cardioverter defibrillator (ICD) was not implanted given his inotrope dependence. He continues to live on palliative home milrinone currently, two years since its initiation. He has been in permanent atrial fibrillation, but his heart rates uptrended to 140–150 bpm a year ago; hence, he was cautiously reinitiated on amiodarone. He remains NYHA Class III, able to perform his activities of daily living independently and with an acceptable quality of life. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on heart failure recommend the use of chronic inotropic therapy as a bridge to cardiac transplantation or mechanical circulatory support (class IIa), or as palliative therapy in patients with stage D heart failure not eligible for mechanical support or transplant (IIb). The use of chronic inotropic therapy has been associated with increased mortality felt to be secondary to an increased burden of ventricular arrhythmias [2]. However, inotropes are routinely used for bridging advanced HF patients to LVAD or transplant, with survival exceeding 90% [3]. ATTRwt amyloidosis generally carries a better prognosis than HF due to AL amyloidosis [4]. Our patient however declined rapidly within a year of diagnosis, eventually admitted with refractory heart failure and cardiogenic shock. Despite significant advances in heart failure therapy including the development of ICDs and LVADs, survival remains relatively suboptimal in patients with amyloidosis [5]. Heart transplantation (HT) and LVAD implantation for patients with amyloid cardiomyopathy have been studied in a few small studies: 1and 2-year survival rates were 86%, and 86% in the HT group [4] and 55% and 44% in the LVAD study [5], respectively. Our patient had an outcome on home milrinone comparable to similar patients undergoing HT or LVAD placement. We used amiodarone for heart rate control in this patient on milrinone with atrial fibrillation. The use of amiodarone is associated with an increased risk of developing heart block in patients with amyloidosis, as compared to patients without amyloid disease, indicating the need for caution and risk/benefit analysis when using amiodarone in these patients [6]. Any therapy that provides symptomatic benefit in advanced heart failure is important and should be considered for palliative purposes. Despite being associated with worse long-term outcomes, inotropic agents do provide symptomatic and likely survival benefit in advanced heart failure patients who are not candidates for LVAD support. This case highlights the successful use of palliative home milrinone for end-stage HF due to advanced cardiac amyloidosis to improve quality and quantity of life, and should be considered prior to adopting hospice.

Preoperative MELD-XI is not Associated with Mortality after LVAD

Background Kidney and liver dysfunction are common in patients with advanced heart failure undergoing left ventricular assistant device (LVAD) implantation. We have previously shown that Model of End-Stage Liver Disease excluding INR (MELD-XI) scores can predict poor outcomes after heart transplantation. Whether MELD-XI predicts outcomes after LVAD implantation is not well understood. Methods All patients who underwent LVAD implantation at a tertiary referral center (2007-2017) were included and preoperative MELD-XI was calculated. Cox proportional hazard models and Kaplan Meier method were used to describe association with overall post-implant mortality. Penalized smoothed splines were used to visualize the association between continuous MELDXI and mortality. Results A total of 94 patients were included. Mean age was 60±13 years, 78% males, 64% Caucasian, 76% had the HeartMate II. Median MELD-XI was 12.4(9.9-15.9). At a median follow-up of 2.8 years, 31 patients died. There was no difference between patients with MELD-XI >12.4 and MELD-XI ≤12.4 in overall mortality ( P =0.14), figure (panel A). There was no association between continuous MELD-XI and mortality (HR 1.04; 95% CI: 0.96-1.13, P =0.32), figure (panel B). Conclusion Our findings showed that MELD-XI is not associated with mortality after LVAD implantation. These findings need to be validated in a larger group registry to identify best bridging strategy in patients with advanced heart failure and combined kidney-liver dysfunction.