Citations

Introduction: Surgically implanted epicardial left ventricular (eLV) lead has been used as an alternative approach when implantation of transvenous LV (tLV) lead in patients requiring cardiac resynchronization therapy (CRT) has failed. Recent literatures noted similarities in clinical response between tLV and eLV-CRT patients. However, comparison between CRT patients with ischemic (ICM) and dilated cardiomyopathy (DCM) is currently lacking in eLV-CRT patients. Hypothesis: We hypothesize that DCM patients respond better to eLV-CRT than ICM patients. Methods: Of 1038 patients who underwent tLV-CRT implantation at UCSD and Mayo Clinics between 2002 and 2013, 44 (Age 63±15, 28M) had failed tLV lead placement and received eLV-CRT. Electronic Medical Records of these patients were reviewed. NYHA class and echocardiograph were assessed before and after successful CRT implantation. Results: Following eLV-CRT implantation, improvements were noted in LVEF (26% vs. 31%, p < 0.01), NYHA class (2.9 vs. 2.3, p < 0.01) and LVESD (57mm vs. 52mm, p = 0.03) in the study cohort. In patients with DCM (n=19), the NYHA class (3.0 vs. 2.3, p = 0.01), LVEF (24% vs. 30%, p = 0.02) and LVESD (57mm vs. 52mm, p = 0.04) had significantly improved following CRT implantation compared to baseline (figures). No statistically significant changes in NYHA class, LVEF and LVESD were observed in patients with ICM (all p > 0.05). Conclusion: In this two-center study, eLV-CRT patients with DCM benefited significantly after CRT, as compared to ICM patients. Although larger scaled studies are needed, eLV-CRT may be considered a viable alternative to tLV-CRT, especially in patients with DCM.

Introduction: Surgically implanted epicardial left ventricular (eLV) lead is an alternative approach when transvenous LV (tLV) lead implantation in CRT patients has failed. With advancement in surgical technique and free from limitations of cardiac venous anatomy, operators have the freedom to choose the most optimal LV pacing site. Recent literatures noted differential clinical response in tLV-CRT patients with different LV lead locations. However, to the best of the authors’ knowledge, no such analysis has been published for eLV-CRT patients. Hypothesis: We hypothesize that optimal LV lead location in eLV-CRT is similar to tLV-CRT and similar clinical response is expected. Methods: After unsuccessful attempt(s) of tLV-CRT implantation, 44 (Age 63±15, 28M) patients received eLV-CRT from UCSD and Mayo Clinics between 2002 and 2013. Two-view (PA, lateral) chest radiographs were used to determine lead location by blinded independent observers. 9 patients were partially excluded from lead location analysis due to congenital cardiac anomaly or unavailable lateral chest radiograph. eLV lead locations were classified as basal, mid, or apical on the PA view; and anterior, anterolateral, lateral, posterolateral, or posterior on the lateral view. Survival data were collected from the national death and location database. Results: During an average follow up of 65 months, 15 patients have died following eLV-CRT implant. No death was attributed to acute surgical complication to eLV-CRT implantation. Kaplan-Meyer survival estimate showed anterior and apical eLV lead positions had lower survival rate as compared to non-anterior (p<0.01, figure A) and non-apical location (p=0.07, figure B). Conclusion: In this two-center study, apical and anterior eLV lead locations were associated with significantly lower survival rate. The study implies apical and/or anterior locations should be avoided, if possible, during eLV-CRT implantation.

Introduction: The treatment options for high and extreme-risk patients with severe symptomatic aortic stenosis have changed significantly over the past decade because of advances in transcatheter aortic valve replacement (TAVR). However new permanent pacemaker implant (PPI) remains an impending concern after TAVR. Hypothesis: We sought to determine the frequency, predictors and outcomes of patients requiring PPI after TAVR. Methods: We queried the National Inpatient Sample (NIS) database using the ICD-9-CM procedure code of 35.05 for transfemoral/transaortic and 35.06 for transapical replacement of aortic valve .We identified TAVR procedures associated with new permanent pacemaker implants using appropriate validated ICD-9-CM codes. Using multivariate analysis we further identified predictors of PPM implants Results: An estimated 8828 TAVR procedures were performed in United States between 2011-2012. 773 (8.7%) TAVR procedures were associated with PPIs. PPI were higher in older (age>80 years), White race, diabetics, left bundle branch block (LBBB), right bundle branch block (RBBB), transfemoral approach. The inhospital mortality ( 5.2% vs.4.6% ) , mean length of stay ( 9.8 vs. 8.3 days ) disposition to short term nursing facility was higher (38.2% vs. 32.1%) and mean total costs (82217$ vs. 52283$) was higher in TAVR + PPI group . On multivariate analysis, Age in 5 year increment [Odds ratio (OR) 1.11; Confidence interval (CI) 1.05-1.17, p<0.001], diabetes [OR 1.26; CI 1.07-1.49, p<0.001], LBBB [OR 1.99; CI 1.55-2.56, p<0.001], RBBB [OR 5.36; CI 3.80-7.55, p<0.001] were independent predictors of PPI. Transfemoral approach was associated with more PPI implants [OR 1.41; CI 1.12 -1.78, p<0.001] Conclusion: Age, baseline conduction system disturbances, diabetes, transfemoral approach emerged as independent predictors of PPI after TAVR. This study provides useful tools to identify high-risk patients for PPI after TAVR.

Introduction Current evidence suggests that abnormal ventriculo-vascular coupling may contribute to the development of atrial fibrillation (AF) by increasing ventricular filling pressures and consequently, left atrial pressure. Recent investigations have also suggested that inflammation might have a role in the pathophysiology of AF. We hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF. Methods In this longitudinal cohort study, residents of Olmsted County, MN with first- time diagnosed AF during 1980-2000 and a reference age- and sex-matched control group from the same underlying population and time period were identified and followed until death, or 2000. The relationship between autoimmune vasculitis and first documented AF was analyzed. Results Of a total of 8766 patients (mean age 61.1+14.9 years; 56% women), 691 (7.9%) were diagnosed with autoimmune vasculitis during the 20 year period. The prevalence of autoimmune vasculitis in the AF group was 9.9% and 5.9% in the control group; p <0.001, respectively. After adjusting for CAD and LV dysfunction, the odds of autoimmune vasculitis in AF was 1.7 times higher than in controls (OR 1.69, 95%; CI 1.42 - 2.01, p < 0.0001). AF patients with autoimmune vasculitis had a worse survival compared to controls; p=.0114 (log-rank test). Conclusion Autoimmune vasculitis strongly increases the risk of atrial fibrillation and portends shorter survival in the AF population. These observations may represent one mechanism linking increased arterial stiffness and inflammation in the pathogenesis and prognosis of AF as an age-related disorder.

Background Little is known about the effects of permanent transvenous device leads on bioprosthetic tricuspid valve (BTV) function. Hypothesis The goal of this study was to test the hypothesis that transvalvular device leads promote clinically significant BTV regurgitation. Methods A retrospective review of 58 patients who underwent BTV implantation and subsequently required endocardial pacemaker (n=52) or defibrillator (n=6) lead implantation through the BTV was conducted. Patient and prosthesis characteristics, lead type, and clinical events were collected. The incidence and severity of prosthetic tricuspid regurgitation (TR), determined by Doppler echocardiography, was compared to 265 patients who underwent BTV implantation without undergoing subsequent transvalvular device lead implantation. Results Over a mean follow up of 25 months, 5 patients (9%) with a transvalvular lead developed ≥ moderate prosthetic TR compared to 12 patients (5%) in the control group (P = 0.20). Kaplan Meier survival analysis revealed no significant difference in the incidence of TR in BTV patients with and without transvalvular leads (p = 0.45). Clinically significant prosthetic TR in patients with and without a transvalvular lead more commonly occurred 2 years or later after lead implantation or BTV implantation (4/5, 80% and 10/12, 83%). Conclusions Compared to BTV controls, there was no significant difference in the incidence of ≥ moderate prosthetic TR in patients with a transvalvular pacemaker or defibrillator lead (p = 0.45). Transvalvular lead implantation appears to be an acceptable approach for patients with a BTV who require permanent pacemaker or defibrillator placement.

Introduction: Cardiac remodeling in heart failure (HF) is associated with conduction abnormalities and dyssynchrony which results in poorly coordinated contractions precipitating metabolic heterogeneity and energetic inefficiency. Cardiac resynchronization therapy (CRT) improves HF symptoms, ventricular function and overall survival. The aim of this study was to determine the changes in metabolomic profiles and substrate utilization after CRT. Methods: 18 patients with advanced HF and 7 healthy controls were included in this study. Blood samples were collected from peripheral vein, femoral artery (FA) and coronary sinus (CS) before and 10-min after CRT. Metabolomic profiling of plasma samples were performed using GC/MS and 1 H NMR spectroscopy. Partial Least Squares Discriminant Analysis (PLS-DA) score plots and regression coefficients were used to examine metabolomic profiles. Results: HF patients have altered plasma metabolomic profile (Fig. A) with distinct panel of metabolites including free fatty acids (FFA), glycerol, 2-hydroxybutyrate, glycine, succinate and uric acid important in group classification compared to controls. Increased release of fumarate and glycerol-3-phosphate from myocardium in HF indicate mitochondrial and substrate shuttle dysfunction. Immediately after CRT, transcardiac metabolomic profile of plasma from CS shifted to a different state with increased myocardial uptake and metabolism of FFA and decreased release of creatinine indicating improved energetic conditions (Fig. B). Conclusion: Metabolomic profiling indicates that CRT improves myocardial substrate metabolism and utilization in patients with advanced HF.

AbstractIntroductionVentricular tachycardia storm or electrical storm (ES) is a common complication following left ventricular assist device (LVAD) implantation. The factors contributing to ES and outcomes are less studied. The study aimed to determine the factors associated with ES and the probability of survival in patients undergoing LVAD in three tertiary centers over a span of 15 years.MethodsWe performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2006 to December 31, 2020. ES was defined as ≥3 episodes of sustained ventricular tachycardia over a period of 24 h with no identifiable reversible cause. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.ResultsA total of 883 patients who underwent LVAD implantation were included in our study. ES occurred in 7% (n = 61) of patients with a median of 13 days (interquartile range [IQR]: 5–297 days) following surgery. We found 57% of patients (n = 35) developed ES within 30 days, while 43% (n = 26) patients developed ES at a median of 545 (IQR 152–1032) days after surgery. Following ES, 26% of patients died within 1 year. Patients with ES had a significant association with a history of ventricular arrhythmias and implantable cardioverter defibrillator (ICD) shocks before the procedure. ES was significantly associated with reduced survival compared to patients without ES (hazards ratio [HR]: 1.92, 95% CI: 1.39–2.64, p < .001).ConclusionFollowing LVAD implantation, the rate of ES was 7% with majority of ES occurring within 30 days of LVAD. Risk factors for ES included pre‐implant history of ventricular arrhythmias and ICD shock. ES was significantly associated with reduced survival compared to patients without ES.

Abstract Background: Circulating tumor cell clusters (CTCCs) are aggregated groups of tumor cells that detached from primary tumors and circulate the bloodstream. However, while Circulating Tumor Cells (CTCs) are a well studied phenomenon, CTCCs remain relatively unexplored and ill-defined, with only a few descriptive investigations evaluating their clinical utility. Adding to CTCC complexity is that various subtypes exist, including homotypic clusters consisting of a homogenous population of tumor cells and heterotypic CTCCs made of CTCs with immune/stromal white blood cells (WBCs). Furthermore, CTCs can undergo Epithelial-Mesenchymal Transition (EMT), a process characterized by loss of epithelial traits and upregulation of mesenchymal traits, and can form clustered EMTs (CEMTs). Moreover, CTCs can fuse with macrophages forming Tumor Macrophage Hybrid Cells, aka Cancer-Associated Macrophage Like cells (CAMLs) when in circulation. We enumerated all these types of cells and complex aggregates in the peripheral blood of patients with metastatic breast cancer (mBC). Methods: We enumerated the 6 populations from patient samples enrolled in IRB aproved prospective pilot studies. Whole peripheral blood (7.5mL) was filtered and stained with cytokeratin (CK) & CD45/CD14 to identify CTCs. CTCs were defined as an intact DAPI nuclei and strong filamentous CK. Homotypic CTCCs were defined as ≥2 CTCs attached together. Heterotypic CTCCs were defined as ≥1 CTC attached to ≥1 WBC. EMTs were defined as having DAPI nuclei and weak non-filamentous CK. CEMTS were defined as ≥2 EMTs. CAMLs were defined as having an enlarged polynucleated DAPI, and positive for CD45/CD14 or non-filamentous CK. Median progression free survival (mPFS) and median overall survival (mOS) over 24 months (m) were evaluated. Results: We evaluated the blood of 79 mBC patients. Single CTCs were found in 57% of patients (n=34/79), homotypic CTCCs 15% (n=12/79), heterotypic CTCCs 66% (n=27/79), EMTs 56% (n=44/79), CEMTs 23% (n=18/79) and CAMLs 97% (n=77/79). Over 24 ms, patierns with detectable heterotypic CTCCs & homotypic CTCCs had the shortest response times at mPFS=2.8 & mOS=5.8 ms, or mPFS=2.1 & mOS=4.3 ms, respectively. This was followed by CTCs mPFS=3.7 & mOS=13.7 ms, EMTs mPFS=4.3 & mOS=14.4 ms, CAMLs mPFS=4.3 & mOS=14.4 ms, and CEMT mPFS=4.7 & mOS=13.2 ms. Additionally, CTCCs were rare in HER2+ patients at 4.4% (n=1/23), but no associations to other hormone statuses were found. Conclusion: CTCCs appear to represent an array of subtypes with different biological and clinical meanings. Here we enumerated CTCC subtypes in the blood of mBC patients and stratified the various types to clinical outcomes. These data suggest CTCCs are clinically important and further understanding of their biology in the context of tumor pathogenesis is needed. Citation Format: Daniel L. Adams, Carolina Reduzzi, Aravind Aryasomayajula, R. Katherine Alpaugh, Saranya Chumsri, Cha-Mei Tang, Giuseppe Del Priore, William V. Williams, Massimo Cristofanilli. Identifying and stratifying circulating tumor cell cluster subtypes in metastatic breast cancer patients and evaluating their clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2303.

Abstract Background Long‐term outcomes of sterile lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) remain unclear. Methods We performed a retrospective study of a population residing in southeastern Minnesota with follow‐up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE of sterile leads from January 1, 2000, to January 1, 2011, and had follow‐up for at least 10 years or until their death were included. Results A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. Indications for subsequent lead extraction arose in 9.1% ( n = 14) of patients with initial LA and 5.3% ( n = 1) in patients with initial TLE, after an average of 7 years. Moreover, 28.6% of patients in the LA cohort who required subsequent extraction did not proceed with the extraction, and among those who proceeded, 60% had clinical success and 40% had a clinical failure. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges (5.2% vs. 5.3%). There was no difference in 10‐year survival probability among the LA group and the TLE group ( p = .64). Conclusion An initial lead abandonment strategy was associated with more complicated subsequent extraction procedures compared to patients with an initial transvenous lead extraction strategy. However, there was no difference in 10‐year survival probability between both lead management approaches.