Need For Cardiac Transplantation Research Articles

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p<0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.

Long-Term Outcomes of Patients With Apical Hypertrophic Cardiomyopathy Utilizing a New Risk Score

BackgroundApical hypertrophic cardiomyopathy (aHCM) is a distinct variant characterized by predominant hypertrophy of the left ventricle apex. ObjectivesThis study sought to describe aHCM patients' characteristics and develop a risk score for aHCM patients. MethodsA total of 462 patients (age 58 ± 15 years, 68% male) diagnosed with aHCM were included. The primary endpoint was death, appropriate defibrillator discharge, or need for cardiac transplantation. Variables showing potential association with the composite endpoint were considered to develop an aHCM-specific risk score. ResultsAt baseline, 67% patients were asymptomatic and 69% had no risk factors for sudden death. On echocardiography, the mean left ventricle ejection fraction, left atrial volume index, and right ventricular systolic pressure were 64% ± 8%, 36 ± 15 ml/m2, and 32 ± 10 mm Hg, respectively, with 51(11%) demonstrating an apical aneurysm. Baseline cardiac magnetic resonance, performed in 246 (53%) patients, demonstrated delayed gadolinium enhancement in 170 (71%) patients (mean percentage of 4.9% ± 6.6%). At age 6.3 ± 4.8 years, the composite events occurred in 80 (17%, death in 62 [13%]) patients. The aHCM-specific risk score, incorporating age, apical aneurysm, left atrial volume index, serum creatinine, and right ventricular systolic pressure, demonstrated good discrimination (C-statistic = 0.75) with an expected to observed ratio of 1.02 and a calibration slope of 0.91. The risk score ranged between 0 and 8 points, with a higher score associated with higher composite events. ConclusionsaHCM constituted 6.8% of our overall HCM cohort with a composite event rate of 2.8%/year. The aHCM risk score provided good discrimination in predicting the composite primary endpoint, with a higher score associated with a higher rate of events.

Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation.

Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited. All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models. The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%). Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.

BIO30: A Method to Monitor Ventricular Recovery Using VAD Signals Based on Parseval’s Power Theorem

Study: Recent studies highlight the growing interest in achieving ventricular recovery for VAD patients, thereby eliminating the need for cardiac transplantation. Hemodynamic measurements may be performed during periodic echocardiography for patients with probable recovery. However, there are no standard methods to evaluate ventricular recovery on a continuous outpatient basis. Such a method can help assess changes in cardiac function throughout daily activities, potentially optimized by a responsive VAD control algorithm. The objective of this study was to evaluate a surrogate measure of cardiac contractility based on VAD inherent signals using an in-silico simulation model of assisted circulation. Methods: Without loss of generality, hemodynamic power can be visualized as an electrical power signal in an implanted VAD. The power of a continuous periodic signal (the VAD Flow Rate signal), given by Parseval’s Power Theorem, is equivalently the average value integral over one period of the square of the magnitude of the signal (inclusive of all harmonic components). In this in-silico simulation study, we compute the ratio of this power with the norm (over multiple cardiac cycles) of the signal under steady-state conditions. We call this ratio the Power Factor of the VAD Flow Rate, represented by λVAD. Numerical simulations were conducted for different values of ventricular contractility (Emax Maximum Ventricular Elastance) from 0.5 to 2.0 mmHg/ml over a range of VAD speeds of 1000 to 8000 RPM (HeartMate 3® VAD Model) in steps of 100 RPM. Results: The figure below illustrates the relationship of the Power Factor to VAD speed for four levels of ventricular contractility. At 1000 RPM, the Power Factor for all Emax values was found to be equal. As the VAD speed increases above approximately 4000 RPM, the λVAD values diverge, demonstrating the direct relationship with Emax: having a peak of approximately 0.8 for the greatest ventricular contractility (Emax = 2.0). As speed increases further and approaches 8000 RPM, the values of λVAD once again converge. Another discriminating feature is the location (speed) of the local maximum (“hump”) in the curves within the range of 4000 and 6000 RPM, with the peak occurring at increasing speeds for increasing contractility. The cause of the hump is due to the cooperative relationship of the VAD and native ventricle, precisely the point of the aortic valve opening, allowing forward flow. At the lowest speeds, there is a slight negative flow through the VAD and, thus, a more subdued λVAD. Conclusion: This simulation study shows that the Power Factor of VAD flow rate has the potential as a noninvasive surrogate measure of ventricular recovery that can be monitored continuously. The metric is sensitive to the interaction between the native left ventricle and the VAD and thus helpful in developing feedback control that optimizes cardiac rehabilitation.Figure 1. Simulation results for the Power Factor of VAD Flow Rate as a function of different VAD Speeds (RPM).

Danish-German cardiogenic shock trial—DanGer shock: Trial design update

BackgroundThe main objective of the Danish German Cardiogenic Shock trial (DanGer Shock ClinicalTrials.gov Identifier: NCT01633502) is to assess the efficacy of the trans valvular axial flow device Impella CP in treating patients with AMICS shock due to STEMI undergoing emergency percutaneous coronary intervention. MethodsThis statistical analysis plan represents an overview of the statistical methods which will be used for analyzing the DanGer Shock trial. ResultsThe primary study endpoint is death from all causes through 180 days in the intention to treat population (all randomized consented patients). The secondary endpoints comprise; composite event of the need for additional mechanical support, need for cardiac transplantation, and death of all causes whichever comes first; and days alive and out of hospital. As exploratory analyses an as treated analysis of primary endpoint will be performed. Composite safety endpoint will comprise of major bleeding, vascular complications, device malfunction, damage to the aortic valve, and significant hemolysis. The primary endpoint death rate at 180 days will be analyzed using Cox proportional hazards analysis. The result will be reported as hazard ratio and corresponding 95% confidence interval (95% CI). No imputation of missing values will be performed. Additional statistical analyses for predefined hemodynamic, metabolic, renal, hematological, and health economics substudies will be specified in separate protocols. ConclusionMain analyses of the primary and secondary outcomes of the DanGer Shock trial will be conducted according to this publication.

Prognostic value of age-sex adjusted NT-proBNP ratio in obstructive hypertrophic cardiomyopathy

BackgroundWe sought to determine the incremental prognostic value of age-sex adjusted N-terminal prohormone brain natriuretic peptide (NT-pro BNP) ratio in obstructive hypertrophic cardiomyopathy (oHCM) patients. MethodsThe study included 2119 consecutive oHCM patients (age 55 ± 13 years, 53% men, maximal LVOT ≥30 mmHg) evaluated between 6/2002–12/2018 with BNP or NT-pro BNP measured at baseline. NT-pro BNP ratio was calculated as: NT-proBNP/ upper limit of normal NT-proBNP derived from age-sex matched controls. Septal reduction therapy (SRT) during follow-up was recorded. Primary endpoint was death, need for cardiac transplantation or appropriate internal cardioverter defibrillator (ICD) discharge. ResultsMedian NT-proBNP ratio was 5.4 (IQR 2.1–12.3). Using spline analysis, log-transformed NT-pro BNP ratio of 2 (corresponding to NT-pro BNP ratio of 6) was the optimal value where primary endpoint hazards crossed 1; there were 966 patients with high and 1153 patients with low NT-pro BNP ratio. 1665 (79%) patients underwent SRT at 47 days (IQR 7–128 days). At 5.4 years of follow-up (IQR 2.8–9.2 years), the primary outcome occurred in 315 (15%) patients (deaths = 270). High NT-pro BNP ratio was associated with higher risk of primary outcome in unadjusted (30.1 vs. 17.2 events/1000 person-year, hazard ratio or (HR) 1.73, 1.37–2.17, P < 0.001) and adjusted analysis (aHR 1.69, 95% 1.19–2.38, P = 0.003) vs. low NT-pro BNP ratio. Even in asymptomatic patients, NT-pro BNP ratio remained associated with primary outcome (aHR 1.28, 95% CI 1.06–1.54, P = 0.01). ConclusionsAge-sex adjusted NT-pro BNP ratio is independently associated with long-term outcomes in oHCM patients, including in a subgroup of asymptomatic patients.

Medical Therapies for Heart Failure in Hypoplastic Left Heart Syndrome.

Significant surgical and medical advances over the past several decades have resulted in a growing number of infants and children surviving with hypoplastic left heart syndrome (HLHS) and other congenital heart defects associated with a single systemic right ventricle (RV). However, cardiac dysfunction and ultimately heart failure (HF) remain the most common cause of death and indication for transplantation in this population. Moreover, while early recognition and treatment of single ventricle-related complications are essential to improving outcomes, there are no proven therapeutic strategies for single systemic RV HF in the pediatric population. Importantly, prototypical adult HF therapies have been relatively ineffective in mitigating the need for cardiac transplantation in HLHS, likely due to several unique attributes of the failing HLHS myocardium. Here, we discuss the most commonly used medical therapies for the treatment of HF symptoms in HLHS and other single systemic RV patients. Additionally, we provide an overview of potential novel therapies for systemic ventricular failure in the HLHS and related populations based on fundamental science, pre-clinical, clinical, and observational studies in the current literature.

Pregnancy and Progression of Cardiomyopathy in Women With LMNA Genotype-Positive.

BackgroundWe aimed to assess the association between number of pregnancies and long‐term progression of cardiac dysfunction, arrhythmias, and event‐free survival in women with pathogenic or likely pathogenic variants of gene encoding for Lamin A/C proteins ( LMNA+).Methods and ResultsWe retrospectively included consecutive women with LMNA+ and recorded pregnancy data. We collected echocardiographic data, occurrence of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, and implantation of cardiac electronic devices (implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator). We analyzed retrospectively complications during pregnancy and the peripartum period.We included 89 women with LMNA+ (28% probands, age 41±16 years), of which 60 had experienced pregnancy. Follow‐up time was 5 [interquartile range, 3–9] years. We analyzed 452 repeated echocardiographic examinations. Number of pregnancies was not associated with increased long‐term risk of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, or implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator implantation. Women with previous pregnancy and nulliparous women had a similar annual deterioration of left ventricular ejection fraction (−0.5/year versus −0.3/year, P=0.37) and similar increase of left ventricular end‐diastolic diameter (0.1/year versus 0.2/year, P=0.09). Number of pregnancies did not decrease survival free from death, left ventricular assist device, or need for cardiac transplantation. Arrhythmias occurred during 9% of pregnancies. No increase in maternal and fetal complications was observed.ConclusionsIn our cohort of women with LMNA+, pregnancy did not seem associated with long‐term adverse disease progression or event‐free survival. Likewise, women with LMNA+ generally well‐tolerated pregnancy, with a small proportion of patients experiencing arrhythmias.

Pregnancy history and long-term progression of cardiomyopathy in LMNA genotype-positive women

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Precision Health Center for optimized cardiac care (ProCArdio), Oslo, Norway Fripro gene positive, Norwegian Research Council, Oslo, Norway Background Competitive and non-competitive exercises have been reported to be deleterious on prognosis of LMNA genotype-positive patients. Comparable to exercise, pregnancy is a prolonged hemodynamic stress situation. Aims We aimed to assess the association between pregnancy history and long-term progression of cardiomyopathy in women with pathogenic or likely pathogenic variants of LMNA (LMNA+). Methods We retrospectively included consecutive LMNA+ females and recorded pregnancy data. We analyzed repeated echocardiographic examinations, including data on left ventricular (LV) end-diastolic diameter (EDD), LV ejection fraction (EF) and LV global longitudinal strain (GLS). We recorded the occurrence of atrial fibrillation (AF), atrioventricular block, sustained ventricular arrhythmias (VA), and implantation of cardiac electronic devices (ICD/CRT-D). We analysed retrospectively complications during pregnancy and peripartum period. Results We included 89 LMNA+ women (28% probands, age 41 ± 16 years), of which 60 had history of pregnancy. Follow-up duration was 5 [IQR: 3-9] years. We analysed 452 repeated echocardiographic examinations. Women with previous pregnancy and nulliparous had a similar annual deterioration of LV EF (-0.5/year vs -0.3/year, p = 0.37, figure left panel), LV GLS (0.1/year vs 0.0/year, p = 0.35, figure right panel) and LV EDD (0.1/year vs 0.2/year, p = 0.09). Number of pregnancies was not associated with increased long-term risk of AF, atrioventricular block, sustained VA or ICD/CRT-D implantation. Pregnancy history was not associated with worse survival free from death, left ventricular assist device or need for cardiac transplantation. Arrhythmias occurred in 9% of pregnancies. No increase of maternal and fetal complications was observed. Conclusions In our cohort of LMNA+ women, pregnancy was not associated with long-term adverse progression of cardiac dysfunction, worsening in arrhythmic progression or reduced event-free survival. Likewise, LMNA+ women generally tolerated pregnancy well, with a small proportion of patients experiencing arrhythmias. Abstract Figure.

The association between mean arterial pressure and outcomes in patients with cardiogenic shock: insights from the DOREMI trial.

Cardiogenic shock (CS) is a state of low cardiac output resulting in end-organ hypoperfusion. Despite high in-hospital mortality rates, little evidence exists regarding the optimal mean arterial pressure (MAP) target in CS. We therefore evaluated the relationship between achieved MAP and clinical outcomes in patients with CS. We performed a post hoc analysis of the CAPITAL DOREMI trial: a randomized, double-blind trial comparing dobutamine to milrinone in patients with CS. We divided patients into a high MAP group (average MAP ≥ 70 mmHg over the 36 h following randomization), and a low MAP group (average MAP < 70 mmHg). Our primary outcome included in-hospital all-cause mortality, resuscitated cardiac arrest, need for cardiac transplantation or mechanical circulatory support, non-fatal myocardial infarction, transient ischaemic attack or stroke, or initiation of renal replacement therapy. In total, 71 (37.0%) patients achieved an average MAP < 70 mmHg, and 121 (63.0%) achieved an average MAP ≥ 70 mmHg. The primary outcome occurred in 48 (67.6%) patients in the low MAP group and 51 (42.2%) patients in the high MAP group [adjusted relative risk (aRR) 0.70; 95% confidence interval (CI) 0.53-0.92; P = 0.01]. All-cause mortality occurred in 41 (57.8%) and 35 (28.9%) patients in the low and high MAP groups, respectively (aRR 0.56; 95% CI 0.40-0.79; P < 0.01). There were no significant differences in any secondary outcomes between each group. In patients with CS treated with inotrope therapy, low MAP is associated with worse clinical outcomes. Randomized data evaluating optimal MAP targets in CS is needed to guide medical therapy.

Hydroxychloroquine and Chloroquine Induced Cardiomyopathy: A Concise Review

Hydroxychloroquine and Chloroquine are commonly used for the treatment of malaria and autoimmune conditions. Most recently, hydroxychloroquine has been implicated in the treatment armamentarium of Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus-2. A rare, underreported side effect of hydroxychloroquine and chloroquine is cardiotoxicity. The cardiomyopathy occurs as a result of inhibition of lysosomal enzymes causing lysosomal dysfunction and intra-cellular accumulation of metabolic byproducts in the myocardium, leading to hypertrophy with or without restrictive physiology and resultant conduction abnormalities. Based on our review of 57 reported cases of hydroxychloroquine or chloroquine induced cardiomyopathy, dyspnea was the most common associated symptom. The most common rhythms seen on EKG were as follows: complete heart block (18.75%), right bundle branch block (RBBB) (18.75%). The most common findings on echocardiography were left ventricular hypertrophy (LVH) (54%), systolic dysfunction (48%) and diastolic dysfunction (32%). A definitive diagnosis is established by endomyocardial biopsy which demonstrates the presence of curvilinear inclusion bodies. The outcome following cessation of the offending agent ranges from complete reversal in 45% of the cases to continued progression with need for cardiac transplantation or even death in 17.5% of the cases.

The Tricuspid Valve in Single-Ventricle Patients: Forgotten, Unforgivable, and Indispensable

The Tricuspid Valve in Single-Ventricle Patients: Forgotten, Unforgivable, and Indispensable

Morbid Obesity as a Therapeutic Target for Heart Failure.

This review will define morbid obesity and relationship between morbid obesity and heart failure syndromes. It will delve into unique challenges facing patients with dual diagnoses of heart failure and morbid obesity and examine the data that obesity should be a target in the treatment of heart failure. Emerging literature has indicated the safety and efficacy of surgical weight loss in patients with heart failure. Furthermore, bariatric surgery with associated weight loss has been associated with improvements in heart failure symptoms and reverse remodeling on echocardiography. In patients with advanced heart failure, bariatric surgery has led to improvement in heart failure to obviate the need for cardiac transplantation or sufficient weight loss for cardiac transplant eligibility. In heart failure patients who are morbidly obese, treatment of obesity is an effective therapeutic target with a myriad of potential benefits.

Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation

The clinical profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients with late presentation is unknown. The purpose of this study was to characterize the genotype, cardiac phenotype, and long-term outcomes of ARVC/D patients with late presentation (age ≥50 years at diagnosis). Five hundred two patients with an ARVC/D diagnosis from Johns Hopkins and Utrecht Registries were studied and long-term clinical outcomes ascertained. Late presentation was seen in 104 patients (21%; 38% PKP2 carriers); 3% were ≥65 years at diagnosis. Sustained ventricular tachycardia was the major (43%) mode of presentation in patients with late presentation, whereas cardiac syncope was infrequent (P<.001). Those with late presentation were significantly less likely to harbor a known pathogenic mutation (53%; P = .005), have less precordial T-wave repolarization changes (P <.001), and have lower ventricular ectopy burden (P = .026). Over median 6-year follow-up, 68 patients with late presentation (65%) experienced sustained ventricular arrhythmias, with similar arrhythmia-free survival at 5-year follow up (P = .48). Left ventricular dysfunction and heart failure were seen in 24 (32%) and 15 patients (14%), respectively, without need for cardiac transplantation. In the late presentation cohort, male sex, pathogenic mutation, right ventricular structural disease, lack of family history, and electrophysiologic study inducibility were associated with increased arrhythmic risk. One-fifth of all ARVC/D patients present after age 50 years, often with sustained ventricular tachycardia, and are less likely to have prior syncope, ECG changes, ventricular ectopy, or identifiable pathogenic mutation. In ARVC/D, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk.

216-53: Clinical and Genetic Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy / Dysplasia Patients in Saudi Arabia: A Single Centre Experience

Background: Arrhythmogenic Right Ventricular Dysplasia / Cardiomyopathy (ARVD/C) is an inherited progressive cardiomyopathy. We aimed to define the long-term outcome and genetic characteristics in a cohort of 31 patients with ARVD/C in a single tertiary care cardiac center in Saudi Arabia. Methods and Results: We enrolled in the study 31 patients with ARVD/C based on the revised 2010 ARVD/C Task Force Criteria (TFC), 25 males (80.65%), age at presentation 7 to 54 years (mean 31.8 ± 13.5 year, median 33 years). Patients presented predominantly with sustained ventricular tachycardia (VT) (48.4%), and syncope (25.8%). Three patients were survivors of cardiac arrest (9.7%). Over a mean follow up of 6.9± 7 years, and a median follow-up of 6 years, 10 of the 31 patients (32.25%) experienced sustained VT. Sudden cardiac death (SCD) during follow-up occurred in one patient without an ICD (3.22%), and one ICD patient (3.22%) died 5 years after ICD implantation because of heart failure. Overall, cardiac mortality and/or the need for cardiac transplantation were low (6.45% and 3.2%, respectively). Genetic testing was performed in 21 patients (67.7%), and 92 family members. Mutations were identified in 9 patients (42.8%), with most common mutation of PKP2 (7 patients). DSP mutation was found in 1 patient as was DCS2 mutation. Conclusions: ARVD/C long-term outcome was favorable in Saudi patients diagnosed and treated in our center and not different from what has been reported from other series. Genetic testing showed PKP2 gene to be the commonest gene defect in our patient.

P2 Outcomes in adults following anatomic repair of congenitally corrected transposition of the great arteries

<h3>Introduction</h3> Anatomic repair (double switch operation) for congenitally corrected transposition of the great arteries (ccTGA) is associated with good short to mid-term outcomes. An increasing number of these patients are surviving to adulthood. There is a paucity of data in adults regarding late sequelae. We sought to determine the long-term outcomes in older patients who have previously undergone a double switch operation for ccTGA. <h3>Methods</h3> A retrospective analysis of 16 patient records from 2001 to 2015 from a single institution was conducted. Median age was 23 years (range 18–56 years, 14 male). Six patients had undergone a Senning-arterial switch and 10 patients underwent a Rastelli-Senning procedure. Associated defects included VSD (n = 13), pulmonary stenosis (n = 2) and pulmonary atresia (n = 13). Three patients had undergone prior pulmonary artery banding and 7 patients systemic-pulmonary artery shunting. We determined freedom from re-operation/intervention, development of systemic left ventricular (LV) dysfunction, systemic mitral regurgitation, conduction disorders and arrhythmias. <h3>Results</h3> Median follow-up was 19 years (18–21 years). Eleven patients required further surgery with 4 patients having undergone two subsequent operations. Following anatomic repair, median time to 1^st operation was 11 years (7–13 years). Indications for re-operation included re-do RV-PA conduit in the Rastelli-Senning patients (n = 8) and aortic valve replacement in the Senning-arterial group (n = 3). 5 patients developed atrio-ventricular conduction block requiring a pacemaker. Three patients developed atrial arrhythmias, with 2 requiring ablation procedures. Six patients developed LV dysfunction. There were no deaths or need for cardiac transplantation in this series. <h3>Conclusion</h3> The majority of patients required a second operation, largely in the Rastelli-Senning group. In the Senning-arterial group, late aortic valve insufficiency occurred in 50% of the patients. Conduction disease and atrial arrhythmias contribute to late morbidity in these patients. Nevertheless, the majority of patients are free of heart failure. Despite good short-term outcomes and survival following anatomic repair, careful long-term evaluation for structural and electrophysiological abnormalities is required.

Abstract 18417: Clinical Presentation, Cardiac Phenotype and Long Term Prognosis of Patients With Late Onset Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Introduction: The phenotypic features and clinical course of elderly Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) patients (age&gt; 50 years at diagnosis) is unknown. Methods: Demographic, phenotypic and genotypic data of 502 patients with ARVC diagnosis (2010 Task Force Criteria) from Johns Hopkins and Utrecht (NL) ARVD/C registries was obtained and long term clinical outcomes ascertained. Results: Late presentation was seen in 104 (21%) patients (38% with PKP2 mutation; no DSP or DSG2 mutation carrier) with 3% being ≥ 65 years at diagnosis. Sustained ventricular tachycardia (VT) is the major (43%) mode of presentation in the elderly while cardiac syncope is infrequent (p&lt;0.001). The elderly are significantly less likely to harbor a pathogenic mutation (53%; p=0.005), have precordial T wave repolarization changes (p&lt;0.001) and have lower ventricular ectopy burden (median count 1503 vs 2497; p=0.026) compared to younger patients. In the elderly, over 7±5 years of follow up, 68(65%) patients experienced sustained ventricular arrhythmias with similar (p=0.08) arrhythmia free survival at 5 years of follow up (73% vs.60% in younger). LV dysfunction and heart failure was seen in 24(32%) and 15(14%) patients respectively without need for cardiac transplantation. Male gender (OR 2.12, 95%CI (1.3-3.45); p=0.002), absence of a pathogenic mutation (OR 1.94, 95%CI (1.20, 3.12); p=0.006) and family member status (OR 2.09, 95%CI (1.24, 3.51); P=0.006) were independently associated with late presentation. In the elderly, EP study inducibility (&lt;0.001), major RV structural disease (p=0.022), absent family history (p&lt;0.001), male gender (p=0.002) and pathogenic mutation (p=0.001) were associated with increased risk of ventricular arrhythmias while ECG abnormalities and ventricular ectopy (p=0.489) were not. Conclusion: One fifth of all ARVD/C patients present after 50 years of age, often with sustained VT and are less likely to have prior syncope or identifiable pathogenic mutation. In ARVD/C, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk. Electrocardiographic changes and ventricular ectopy are significantly less common in the elderly and are not associated with arrhythmic events.

Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a progressive cardiomyopathy. We aimed to define long-term outcome in a transatlantic cohort of 1001 individuals. Clinical and genetic characteristics and follow-up data of ARVD/C index-patients (n=439, fulfilling of 2010 criteria in all) and family members (n=562) were assessed. Mutations were identified in 276 index-patients (63%). Index-patients presented predominantly with sustained ventricular arrhythmias (268; 61%). During a median follow-up of 7 years, 301 of the 416 index-patients presenting alive (72%) experienced sustained ventricular arrhythmias. Sudden cardiac death during follow-up occurred more frequently among index-patients without an implantable cardioverter-defibrillator (10/63, 16% versus 2/335, 0.6%). Overall, cardiac mortality and the need for cardiac transplantation were low (6% and 4%, respectively). Clinical characteristics and outcomes were similar in index-patients with and without mutations, as well as in those with familial and nonfamilial ARVD/C. ARVD/C was diagnosed in 207 family members (37%). Symptoms at first evaluation correlated with disease expression. Family members with mutations were more likely to meet Task Force Criteria for ARVD/C (40% versus 18%), experience sustained ventricular arrhythmias (11% versus 1%), and die from a cardiac cause (2% versus 0%) than family members without mutations. Long-term outcome was favorable in diagnosed and treated ARVD/C index-patients and family members. Outcome in index-patients was modulated by implantable cardioverter-defibrillator implantation, but not by mutation status and familial background of disease. One third of family members developed ARVD/C. Outcome in family members was determined by symptoms at first evaluation and mutations.

MODERATE/SEVERE DIASTOLIC DYSFUNCTION IS ASSOCIATED WITH WORSE OUTCOME IN PATIENTS WITH LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS AND LOW EJECTION FRACTION -Results OF THE TOPAS STUDY

s S243 368 CIRCULATING BIOMARKER RESPONSES TO MEDICAL MANAGEMENT VERSUS MECHANICAL CIRCULATORY SUPPORT IN SEVERE INOTROPE-DEPENDENT ACUTE HEART FAILURE A Meredith, L Dai, V Chen, M Seidman, Z Hollander, R Ng, J Wilson-McManus, A Kaan, S Tebbutt, K Ramanathan, A Cheung, B McManus Vancouver, British Columbia BACKGROUND: Severe inotrope-dependent acute heart failure (AHF) is associated with poor clinical outcomes, and blood biomarkers to guide therapy could improve management of this condition. There are currently no well-defined biomarkers of response to treatment that can be used to guide treatment or evaluate recovery in this patient population. APPROACH: In the present study we characterized the levels of novel and emerging circulatingHF biomarkers of HF in patients with severe inotrope-dependent AHF over the first 30 days of medical management or mechanical circulatory support (MCS). We hypothesized that there would be a shared treatment response identifiable in both patient groups, particularly a plasma proteomic signature of inotrope-dependent AHF reversal. DESIGN AND METHODS: We enrolled a prospective cohort of 25 consecutive patients >19 years of age and supported on at least one inotrope, admitted to St. Paul’s Hospital with AHF. Peripheral blood samples were collected at days 1, 7 and 30 post-admission. Analysis of peripheral blood proteomic biomarkers was performed using semi-targeted multiple reaction monitoring mass spectrometry (MRM) and candidate marker antibody arrays. A subset of patients managed medically who survived to 30 days post-admission without the need for cardiac transplantation or mechanical circulatory support (n1⁄48), and patients receiving implantable MCS (n1⁄45) were selected for this analysis. Time course plasma samples from the first 30 days of therapy underwent biomarker analyses to generate biomarker signatures characteristic of the response to each treatment modality. Differentially expressed proteins were identified using robust limma with p <0.05 and a false discovery rate (FDR) <0.05 for MRM and antibody array data. RESULTS: We identified a set of 6 in-common plasma proteins which are differentially regulated in both treatment groups, and two proteins uniquely associated with each therapeutic intervention. Patients managed medically or with implantable MCS had increases in circulating cardiotrophin 1, cardiac troponin T, clusterin, and dickopff 1. Levels of c-reactive protein and growth differentiation factor 15 decreased in both groups over the 30-day time course. CONCLUSION: We have characterized the temporal proteomic signature of clinical recovery in AHF patients managed medically or with MCS, over the first 30 days of treatment. Changes in biomarker expression over the time course may enhance understanding of the biological basis of AHF, including the identification of novel markers and mechanisms of recovery. NCE, CECRP

Beta-blockers Associated with a Mortality Benefit in Patients with Systolic Dysfunction and Elevated Serum Bilirubin.

Background: Hyperbilirubinemia is associated with increased mortality in heart failure (HF) patients. We evaluated the impact of evidence-based medical therapy, in particular beta-blocker on the survival of patients with HF and hyperbilirubinemia.Methods and Results: We reviewed the charts of all patients followed at our tertiary care heart failure clinic. Hyperbilirubinemia was defined as total bilirubin >30 µmol/L (1.5 times the upper limit of our laboratory value). The primary endpoint was all-cause mortality. The secondary endpoint was a composite of death, cardiac transplant or ventricular assistance device implantation (VAD). Of 1035 HF patients, 121 patients (11.7%) had hyperbilirubinemia. Median follow-up was 556 days. Hyperbilirubinemia was associated with an eight-fold increase in all-cause mortality, hazard ratio (HR): 8.78[95% Confidence Intervals (CI): 5.89-13.06]. Beta-blocker use was associated with approximately 60% reduction in all-cause mortality (HR: 0.38, 95% CI:0.15-0.94) and 70% reduction in the composite secondary endpoint (HR:0.31, 95% CI:0.13-0.71) in patients with hyperbilirubinemia.Conclusion: HF patients with hyperbilirubinemia have increased early mortality, need for cardiac transplantation or VAD. Beta-blocker use was associated with early survival benefit in these patients. Bilirubin levels should be monitored in patients with HF and early initiation of beta-blockers in patients with hyperbilirubinemia should be considered.