Chahal, C. Anwar A.

Abstract Background Orthotopic heart transplant (OHT) is indicated for end-stage heart failure due to cardiac sarcoidosis (CS). However, utilization of OHT for CS has been controversial due to concern for involvement of other organs by sarcoidosis affecting long term outcomes. Purpose Our objective was to study the trends in OHT in patients with CS in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014. Methods Using NIS data, we identified patients older than 18 years with cardiac sarcoidosis using codes ICD 9-CM codes of 135 and 425.8. Among these patients, we identified those who underwent cardiac transplantation using ICD 9-CM procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results A weighted total of 24231 hospitalizations for CS was extracted from 1999 to 2014 of which 248 (1.02%) CS patients underwent OHT. The trends in cardiac transplant for CS is as shown in Figure 1. The mean age of CS patients undergoing OHT was 51.7±1.1 years and 60.4% (n=150) were males. 114 (45.9%) were Caucasians and 27.8% (n=25) were African-American. 100% of the transplants were performed at medium (n=5) or large sized (n=243) teaching hospitals and 97.9% of cardiac transplants were also done at teaching hospitals. Heart transplants were mostly done in the South (36.3%) followed by Midwest (26.2%), West (25%) and Northeast (12.5%). Private insurance was the major payor source which covered 149 (60.1%) patients followed by Medicare covering 65 (26.2%) patients. A total of 10 (3.9%) cardiac sarcoidosis patients died during the same hospitalization for cardiac transplantation. Following OHT, 84.2% (n=209) were discharged home and 11.6% (n=29) to short term hospitalization. The mean cost of hospitalization for OHT in CS when adjusted for inflation was 535144±56060 dollars while the average length of stay for heart transplant for CS was 46.2±6.6 days. Conclusions Cardiac transplant trends in CS have not changed from 1999 to 2014 despite recent studies showing improved outcomes and are associated with substantial cost of hospitalization and length of stay. Majority of cardiac transplant was done in Caucasians despite cardiac sarcoidosis being more common in African-Americans. Funding Acknowledgement Type of funding source: None

Abstract Background Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation of transplanted heart with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and risk of allograft rejection may result in change in the prevalence of arrhythmias in transplanted hearts. Purpose To describe the trends, distribution and the clinical impact of arrhythmias in transplanted hearts in a large nationwide population. Methods We queried the National Inpatient Sample with administrative codes. Cardiac transplant patients were identified using procedure ICD-9-CM codes 37.5 and 33.6. Common arrhythmias were extracted using appropriate validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis of data. Results There was a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States and 16342 (54.4%) of these had arrhythmias. The prevalence of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. The most common arrhythmia was atrial fibrillation (26.83%) followed by ventricular tachycardia (22.86%) and the prevalence of individual arrhythmias is as shown in Figure 1. Cardiogenic shock was higher in transplanted hearts with arrhythmias when compared with patients without arrhythmias (25.96% vs 18.18%; p<0.001). Transplant recipients with arrhythmias were also associated with an increased use of mechanical circulatory device (18.22% vs 12.67%, p<0.001). The use of implantable cardiac defibrillators and permanent pacemaker was also higher in the arrhythmia group (2.19% vs 0.63% and 40.43% vs 30.24% respectively, p<0.0001). However, there was no significant difference in inpatient mortality between transplant recipients with arrhythmias and without arrhythmias (7.72% vs 6.90%, p=0.225). Further, there was no significant difference in frequency of strokes between the groups (4.98% vs 5.08%; p=0.857). The total hospital cost when adjusted for inflation was significantly higher in the arrhythmic patients, with an average cost of about $570,415±9,590 vs $439,707±8362 in patients without arrhythmias (p<0.0001). The mean length of hospitalization was 44.2±0.8 days in patients with arrhythmias compared to 33.9±0.8 days in patients without arrhythmias (p<0.0001). Conclusion A significant proportion of patients with heart transplant have cardiac arrhythmias and are associated with worse in-hospital outcomes of cardiogenic shock, increased length of stay, and cost of hospitalization. However, they are not associated with worse inpatient mortality. Funding Acknowledgement Type of funding source: None

Abstract Introduction Cardiopulmonary exercise testing (CPET) has an established role in the clinical evaluation of exercise intolerance and in the risk stratification of patients with heart failure. There is limited data assessing its prognostic utility in the evaluation of patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). The predisposition of patients with ARVC for ventricular arrhythmias and sudden cardiac death has led to recommendations for exercise restrictions and limits our understanding of how the impairment in oxygen extraction and cardiac output impact disease progression and outcomes in these patients. Purpose We examined the association between CPET indices and event free survival (time to mortality or cardiac transplantation) in patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Methods Patients with definite ARVC based on 2010 task force criteria and genetically positive were enrolled into our institutional ARVC registry. 43 patients underwent CPET and have been included in our analyses. Indications for testing included: Evaluation of exercise-induced palpitations/arrhythmias or syncope (37%), pharmacotherapy optimization (28%), heart failure evaluation (19%), and ARVC management decisions (16%). CPET data (peak oxygen consumption (pVO2), respiratory exchange ratio (RER), and ventilatory efficiency (VE/VCO2) were assessed in patients at time of initial evaluation. Median follow-up time was 4.9 years (IQR 9 years). Results 126 patients were studied (age 43.7+ 15 yrs; 41% women; LVEF 57+ 11%; 15% with LVEF <50%) and 43 underwent CPET evaluation. 41 patients (95%) performed at near maximal effort (RER >1) and no fatal events were reported during testing. During the follow up period, the outcome (death or cardiac transplantation) occurred in 31 patients. On Kaplan Meier analysis, pVO2 ≤14 mL/kg/min was associated with worse outcomes (unadjusted p<0.001). Peak oxygen consumption (pVO2) ≤14 mL/kg/min and ventilatory efficiency (VE/VCO2) >34 were associated with shorter event free survival (HR 5.58, p=0.002 and HR 5.56 p=0.005, respectively). After adjusting for age, sex, and right ventricular function, the association between peak oxygen consumption (pVO2) and event free survival remained significant (p=0.02). Conclusions In patients with ARVC, peak oxygen consumption (pVO2) was a prognostic indicator of worse outcomes. Our findings suggest a potential role for pVO2 in disease surveillance and early assessment for advanced heart failure therapies. Figure 1. KM plot pVO2 & event free survival Funding Acknowledgement Type of funding source: Other. Main funding source(s): Mayo Clinic

Abstract Background Takotsubo cardiomyopathy (TC) is a reversible stress-induced myocardial dysfunction with increased sympathetic activity caused by excessive release of catecholamines playing a central role in its pathophysiology. The occurrence of TC in transplanted hearts is rare given the complete denervation done during transplantation. However, it has been demonstrated that 40% of transplant recipients undergo sympathetic re-innervation. There have only been case reports describing TC in post-transplant recipients. Purpose To evaluate the incidence, baseline characteristics and outcomes of TC occurring in heart transplant recipients using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) in United States from 2009 to 2014. Methods Using NIS data, we identified patients who underwent cardiac transplantation using ICD9 procedure codes 37.5 and 33.6. Among these patients, we identified those admitted to the hospital with diagnosis of TC based on ICD-9-CM code 429.83. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results We identified 257 hospitalizations for TC in heart transplant recipient patients. There was an approximately 9-fold increase in admissions from 11 in 2009 to 95 in 2014. Among patients with TC, the mean age was 65.3±1.8 years and majority were female (76.6%). A majority of patients were Caucasians (63%) followed by smaller proportion of African-Americans (13.2%). In-patient mortality in patients admitted with TC following heart transplant was 11.3% (n=29). During the hospitalization, 4.8% of patients had cardiogenic shock and 2.8% required mechanical circulatory support. The average length of stay for patients with TC was 16.6±3.3 days. The mean cost of hospitalization for these patients when adjusted for inflation were 237248±55709 dollars. Conclusion TC can still occur in substantially in heart transplant recipients and should be considered one of the differential diagnosis in transplant patients presenting to the hospital. Funding Acknowledgement Type of funding source: None

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterised by ventricular arrhythmia and an increased risk of sudden cardiac death (SCD). Numerous genetic determinants and phenotypic manifestations have been discovered in ACM, posing a significant clinical challenge. Further to this, wider evaluation of family members has revealed incomplete penetrance and variable expressivity in ACM, suggesting a complex genotype-phenotype relationship. This review details the genetic basis of ACM with specific genotype-phenotype associations, providing the reader with a nuanced perspective of this condition; whilst also proposing a future roadmap to delivering precision medicine-based management in ACM.

AbstractBackgroundPatients with cardiac amyloidosis (CA) have increased mortality, which can be explained in part by an increased risk of arrhythmias. The burden of arrhythmias in CA, their predictors, and impact on in‐hospital outcomes remains unclear. The role of implantable cardioverter‐defibrillators (ICD) in this population is also uncertain.MethodsWe queried the National Inpatient Sample (NIS) using ICD‐9‐CM codes 277.39 and 425.7 to identify CA. Twelve common arrhythmias were extracted using appropriate, validated ICD‐9‐CM codes. ICD implantation was identified using procedure ICD‐9 codes 37.94 to 37.98, 00.51 and 00.54.ResultsThere were a total of 145,920 CA hospitalizations between 1999 and 2014 in the United States and 56,199 (38.5%) of them were associated with arrhythmias. The prevalence of arrhythmias remained relatively constant from 41.5% in 1999 to 40.2% in 2014. The most common arrhythmia was atrial fibrillation (25.4%). In‐patient mortality was significantly higher in CA patients with arrhythmias (10.4% vs 6.5%, P < .001). ICD implantation was performed in 1,381 (0.94%) patients with CA and analysis revealed an incremental trend in implantation over the study period (0.48% in 1999 to 0.65% in 2014). In‐hospital mortality was significantly lower in patients who underwent ICD implantation (3.7% vs 8%; P = .0078). CA patients with arrhythmias also had an increased cost of hospitalization and length of stay ($65,046 ± 1,079 vs $53,322 ± 687 and 8.3 ± 0.1 vs 7.4 ± 0.1 days, respectively; P < .0001).ConclusionCardiac arrhythmias are common in patients with CA and are associated with worse in‐hospital outcomes, increased length of stay, and cost of hospitalization.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and sleep disordered breathing (SDB) is a treatable risk factor that has been seen to occur concurrently, and is known to propagate mortality and morbidity in a number of cardiovascular disease states including heart failure, and indeed hypertrophic cardiomyopathy. In this review, we summarize past studies that explored the simultaneous occurrence of HCM and SDB, and the pathophysiology of SDB in relation to heart failure, arrhythmias, cardiac ischemia and pulmonary hypertension in HCM. The current therapeutic modalities, with the effect of obstructive sleep apnea (OSA) treatment on HCM, are then discussed along with potential future directions.