Citations

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 Cardiac amyloidosis (CA) remains an underdiagnosed entity. Atrial fibrillation (AF) is common in patients with CA, likely owing to direct amyloid deposition in the left atrium. However, the prevalence of AF in CA and its association with in-hospital outcomes has not been studied in large populations. Purpose Our aim was to study the trends, baseline characteristics, and clinical impact of AF in patients with CA in the United States using the Healthcare Cost and Utilization Project (HCUP) National) Inpatient Sample (NIS) from 1999 to 2014. Methods We queried the NIS and identified CA using ICD-9-CM codes 277.39 and 425.7. AF in CA patients was identified using the ICD-9-CM code of 427.31. Statistical Analysis System (SAS) 9.4 was used for analysis of data. Results There were a total of 145,920 CA hospitalizations between 1999 and 2014 in the United States, of which 37,070 (25.4%) had AF. The prevalence of AF remained consistent from 27.5% in 1999 to 27.4% in 2014. The mean age of patients with AF was 72.9±28.2 years and for patients without AF was 67±31.9 years (p<0.0001). The majority of the patients with AF were male (60.3%) and the study group was predominantly white (62.8% in patients with AF and 56.4% in patients without AF). CA patients with AF suffered more from thyroid-related disease (22.5% vs 16.1%), heart failure (62.9% vs 36.5%) and renal failure (34.7% vs 30.5%) and less from hypertension (29.3% vs 34.0%) and diabetes mellitus (23.2% vs 25.2%) (p<0.0001). There was no significant difference in the Charlson comorbidity score between the groups. Inpatient mortality was significantly higher in CA patients with AF (10.4% vs 6.5%, p<0.001). However, in-patient mortality has been decreasing over the years from 10.3% in 1999 to 7.6% in 2014. Furthermore, cardiogenic shock was significantly higher in CA patients with AF (2.1% vs 1.2%, p<0.001), yet the use of mechanical circulatory support was not significantly different between the groups (0.42% vs 0.35%, p=0.375). Pacemaker implantation was also noted to be higher in CA patients with AF compared to patients without AF (2.8% vs 1.2%, p<0.0001). There was no significant difference between CA patients with and without AF in mean cost of hospitalization ($58222±10752 vs $57695±545, p=0.081) or length of stay (7.9±0.1 vs 7.7±0.1 days, p=0.7089). Conclusion CA with atrial fibrillation is a well-recognized entity, and our large scale retrospective analysis found significant association with worse in-hospital outcomes and cardiogenic shock. Interestingly, trend of in-patient mortality in CA has been decreasing over the years, likely owing to improved imaging modalities for diagnosis. Optimal management of AF in CA is imperative to improve outcomes in this population. 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 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

Objective: The aim of this study was to develop a risk score utilizing C-reactive protein (CRP) and procalcitonin to better predict a clinical infection for patients with obstructive urolithiasis. Methods: A retrospective review was performed of patients presenting to the emergency room from December 2017 to February 2019 and who underwent upper urinary tract decompression due to concern for infection in the setting of obstructing urolithiasis. Over 30 clinical parameters were assessed and a composite risk score was created. Univariate and multivariate, forward, stepwise regression analyses were performed to identify predictors of true urinary tract infection (UTI). Results: Ninety-eight patients met inclusion criteria, of which a true UTI was identified in 50 (51%). The standard model of serum white blood cells >15 or temperature >38°C had an area under curve (AUC) of only 0.67 to predict UTI. A multivariable regression-based 4-point risk score (1 point for each of the following: positive urinary Gram stain, perinephric fat stranding on CT, serum CRP >21.95, and serum procalcitonin >0.36) had an AUC of 0.91 to predict UTI. Individually, these components had an AUC of 0.68, 0.68, 0.80, and 0.77, respectively. The chances of confirmed UTI were 8%, 11%, 68%, and 100% for risk scores of 0, 1, 2, and 3 to 4, respectively ( p < 0.001). Conclusions: Only 50% of patients with a suspected UTI and an obstructing stone were ultimately confirmed to have a UTI. A risk score consisting of Gram stain, perinephric fat stranding, CRP, and procalcitonin can improve UTI prediction and warrants further study.

Abstract Improving risk prediction and prevention strategies through identifying new susceptibility genes for non-high-grade serous ovarian cancer (non-HGS) would represent an important advance in reducing incidence and mortality. Epithelial ovarian cancer (EOC) has five main histotypes that have distinct pathologies, molecular changes, clinical characteristics, and tissues of origin. They are classified as high-grade serous (HGS), low-grade serous (LGS), clear-cell (CCC), endometrioid (END), and mucinous (MUC). A family history of breast or ovarian cancer is the strongest single risk factor for EOC. Germline mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2 confer EOC risks of 44% and 17% by age 80, respectively. Only 40% of the excess familial risk is known, suggesting there are many other susceptibility genes yet unidentified. The non-HGS histotypes are poorly studied due to limited sample size within individual studies. Thus, families of cases with non-HGS tumors have few risk prediction options. Whole-exome sequencing (WES) analysis was performed on 251 non-HGS cases (56 LGS, 55 CCC, 117 END, 23 MUC). Cases were screened negative for BRCA1/2 mutations and selected for a family history of ovarian or breast cancer, or young onset (&lt;45 years) of ovarian cancer. WES identified 1,278 genes with rare predicted truncating mutation in at least one case. Predicted truncating mutations in cases were compared to 171,584 controls from the Exome Aggregation Consortium (ExAC) and the Genome Aggregation Database (gnomAD). Gene-set enrichment analysis showed enrichment for genes involved in the DNA repair pathway (p=3.08 × 10−7). Twenty-five candidate genes (including 4 DNA repair genes) were selected for validation by targeted sequencing. Five genes important in HGS (BRIP1, FANCM, PALB2, RAD51C, RAD51D) as well as two additional candidates (XRCC2 and XRCC3) were also sequenced. Targeted sequencing was performed on 1,779 cases (669 END, 356 CCC, 327 LGS, 427 MUC) and 1,863 controls from studies in the Ovarian Cancer Association Consortium (OCAC). Library preparation and target enrichment was performed using the Fluidigm Juno System and Illumina sequencing was performed on a NovaSeq 6000 Sequencing System. A case-control analysis of predicted truncating variants in the 32 genes was performed. Using a minimum alternate allele frequency of 30%, we identified a higher frequency of mutations in non-HGS cases than controls in ERCC6 (p=0.034) and IL31RA (p=0.034). ERCC6 is involved in DNA repair and IL31RA is a cytokine receptor. Sanger sequencing validation of variants to confirm these results is ongoing. Several other genes showed suggestive higher frequencies of mutations in cases than controls. A larger case control analysis will be performed to confirm those findings. Identifying novel susceptibility genes for non-HGS may have clinical impact by reducing disease-associated mortality through improving risk prediction, identifying prevention strategies, and developing new targeted treatments. Citation Format: Marina Pavanello, Ed Dicks, Honglin Song, Amir Ariff, Adelyn Bolithon, Maria P. Intermaggio, Mark Pinese, Kirsten Moysich, Kunle O. Odunsi, Ellen Goode, David D. Bowtell, Peter Fasching, Jennifer A. Doherty, Francesmary Modugno, Susanne K. Kjær, Penelope M. Webb, Anna Wu, Anna deFazio, Ovarian Cancer Association Consortium, Paul James, Deepak Subramanian, Ian Campbell, Simon A. Gayther, Paul D.P. Pharoah, Susan J. Ramus. Germline mutations in new susceptibility genes for non-high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B37.

Abstract Aims Current electrophysiology signal recording and mapping systems have limited dynamic range (DR) and bandwidth, which causes loss of valuable information during acquisition of cardiac signals. We evaluated a novel advanced signal processing platform with the objective to obtain and assess additional information of clinical importance. Methods and results Over 10 canines, we compared intracardiac recordings within all cardiac chambers, in various rhythms, in pacing and during radiofrequency (RF) ablation across two platforms; a conventional system and the PURE EP™ [(PEP); Bio Sig Technologies, Inc., Los Angeles, CA, USA]. Recording cardiac signals with varying amplitudes were consistently and reproducibly observed, without loss of detail or introduction of artefact. Further the amplitude of current of injury (COI) on the unipolar signals correlated with the instantaneous contact force (CF) recorded on the sensing catheter in all the animals (r2 = 0.94 in ventricle). The maximum change in the unipolar COI correlated with the change in local electrogram amplitude during non-irrigated RF ablation (r2 = 0.61 in atrium). Reduction in artefact attributable to pacing (20 sites) and noise during ablation (48 sites) was present on the PEP system. Within the PEP system, simultaneous display of identical signals, filtered differently, aided the visualization of discrete conduction tissue signals. Conclusion Compared to current system, the PEP system provided incremental information including identifying conduction tissue signals, estimates of CF and a surrogate for lesion formation. This novel signal processing platform with increased DR and minimal front-end filtering may be useful in clinical practice.

AbstractBackgroundMagnetic resonance imaging (MRI) in patients with legacy cardiovascular implantable electronic devices (CIEDs) in situ is likely underutilized. We hypothesized the clinical benefit of MRI would outweigh the risks in legacy CIED patients.MethodsThis is a single‐center retrospective study that evaluated and classified the utility of MRI using a prospectively maintained database. The outcomes were classified as aiding in diagnosis, treatment, or both for the patients attributable to the MRI. We then assessed the incidence of adverse effects (AE) when the MRI was performed.ResultsIn 668, MRIs performed on 479 patients, only 13 (1.9%) MRIs did not aid in the diagnosis or treatment of the patient. Power‐on reset events without clinical sequelae in three scans (0.45%) were the only AE. The probability of an adverse event happening without any benefit from the MRI scan was 1.1 × 10−4. A maximum benefit in diagnosis using MRI was obtained in ruling out space‐occupying lesions (121/185 scans, 65.4%). Scans performed in patients for elucidating answers to queries in treatment were most frequently done for disease staging at long term follow‐up (167/470 scans, 35.5%). Conservative treatment (184/470 scans, 39%) followed by medication changes (153/470 scans, 28.7%) were the most common treatment decisions made.ConclusionsThe utility of MRI in patients with non‐MRI‐conditional CIEDs far outweighs the risk of adverse events when imaging is done in the context of a multidisciplinary program that oversees patient safety.

AbstractIntroductionVenous stenosis is a well‐recognized complication of transvenous leads (TVLs) that is encountered during lead revisions or device upgrades. We here report the outcomes of TVL placement facilitated by fibroplasty or tunneling (TUN) procedure.MethodsWe conducted a single‐center retrospective cohort study of all patients undergoing TVL implantation requiring fibroplasty or TUN from 2005 to 2017. Medical records and procedure reports were reviewed for relevant data. Outcomes for fibroplasty and TUN to facilitate TVL placement were compared.ResultsSixty patients had fibroplasty and thirty‐five patients had a TUN procedure. There was no difference in procedure success rates between the two groups (97% fibroplasty vs. 100% TUN; p = .98). The fluoroscopy time was longer (fibroplasty = 39.7 ± 21.5 min vs. TUN = 29.2 ± 21.3 min; p = .01) and the total procedural time was shorter in the fibroplasty group (fibroplasty = 247 ± 77.8 min vs. TUN = 287 ± 77.1 min; p = .01). TUN was associated with a significantly higher incidence of acute complications (fibroplasty = 0 vs. TUN = 8; p = .002) most requiring invasive intervention and/or transfusion with blood products. Long‐term complications requiring additional device‐related procedures were comparable between the two groups (fibroplasty = 6 vs. TUN = 6; logrank p = .21).ConclusionsFor patients with venous stenosis requiring additional TVL, balloon fibroplasty is associated with similar rates of success and a significantly decreased incidence of acute complications when compared with subcutaneous TUN.

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.