Citations

Introduction: Ventricular storms are managed with a combination of antiarrhythmic drugs (AAD) and ablation therapy. This study examines outcomes in patients who required cardiac intensive care unit (CICU) admission for ventricular storms. Methods: A retrospective cohort study was conducted of 200 random adult patients who admitted to the CICU at Mayo Clinic Rochester in 2016-2017 for ventricular storm. Continuous variables were analyzed with the Mann-Whitney U test. Categorical variables were analyzed with Fisher's exact test. Results: Of the 200 patients, 33 (16.5%) patients underwent ablation and AAD therapy for ventricular arrhythmias; 167 underwent AAD therapy alone. The patients in the ablation group were significantly younger (median of 60.3 vs. 72.7, U=1570, p<.001), had a lower Charlson Comorbidity Index (3.56 vs. 5.21, U=1916, p=.005), and a higher BMI (31.6 vs. 28.2, U=2028, p=.032). There was no difference in sex and race (white vs. non-white) between the two groups. The patients in the ablation groups had a significantly lower in-hospital mortality (0% vs. 20%, p=.001) and higher 1-year survival (91% vs. 63%, p=.001). There was no difference in length of stay in the CICU, length of stay in the hospital, or rate of hospital readmission within one year of discharge. Conclusions: Our study indicates that critically ill patients who undergo ablation and AAD for ventricular arrhythmias have decreased mortality compared to patients who underwent AAD therapy alone. More research is needed to elucidate whether this survival benefit is secondary to differences in treatment or baseline comorbidities in the two groups. Table 1: Characteristics and outcomes of patients undergoing ventricular storm treatment. Data is reported either as median or number of occurrences (%). Antiarrhythmic drug (AAD), Charlson Comorbidity Index (CCI), Body Mass Index (BMI), Cardiac Intensive Care Unit (CICU), Length of Stay in days (LOS). * Significance with p values < .05

Introduction: Over 100 FDA-approved medications, electrolyte perturbations, and many disease states can prolong the QTc beyond its 99 th percentile value resulting in acquired QT prolongation. In contrast, approximately 1 in 2000 people have congenital long QT syndrome (LQTS) hallmarked by pathological QT prolongation secondary to genetic defects in the heart. Hypothesis: An artificial intelligence (AI) deep neural network (DNN) can distinguish patients with LQTS from those with acquired QT prolongation. Methods: The study cohort included all patients with LQTS evaluated in the Windland Smith Rice Genetic Heart Rhythm Clinic and controls from Mayo Clinic’s ECG data vault comprising over 2.5 million patients. For the AI-DNN model, every patient/control with ≥ 1 ECG above age- and sex- specific 99 th percentile values for QTc [> 460 ms for all patients (male/female) < 13 years of age, or > 470 ms for men and > 480 ms for women above this age] was included. An AI-DNN involving a multi-layer c onvolutional n eural n etwork (CNN) was developed to classify patients. LQTS patients were age- and sex- matched to controls at 1:5 ratio. Results: Among the 1,599 patients with genetically confirmed LQTS, 808 had ≥ 1 ECG with QTc above the threshold (2,987 ECGs) compared to 361,069/2.5M controls (14% of Mayo Clinic patients getting an ECG, ‘presumed negative’; 989,313 ECGs). Following age- and sex- matching and splitting, 3,309 (training), 411 (validation) and 887 (testing) control ECGs were used. This model distinguished LQTS from those with acquired QT prolongation with an AUC of 0.896 (accuracy 85%, sensitivity 77%, specificity 88%, PPV 0.58, NPV 0.94). After exclusion of patients with a wide QRS (>150 ms) or pacemaker, the model remained successful in distinguishing the two groups (AUC 0.85, accuracy 78%, sensitivity 78%, specificity 87%, PPV 59%, NPV 94%). Conclusions: For patients with a QTc exceeding its 99 th percentile values, this novel AI-DNN functions as a LQTS mutation detector being able to identify patients with abnormal QT prolongation secondary to a LQTS-causative mutation rather than acquired QT prolongation with a >50% positive predictive value. This algorithm may facilitate screening for this potentially lethal, yet highly treatable, genetic heart disease.

Introduction: Limited clinical experience of new trainees has been associated with poor outcomes in the first month of training (July) in teaching hospitals. It remains unclear if this ‘July effect’ continues to be present in contemporary era in patients with acute myocardial infarction (AMI). Methods: Adult hospitalizations for AMI in May and July in urban teaching and non-teaching hospitals in the United States were identified from the HCUP-NIS database (2000-2017). Admissions to rural hospitals, and those without in-hospital mortality data were excluded. In-hospital mortality was compared between those admitted in May and July. A difference-in-difference analysis comparing a change in outcome from May to July in teaching hospitals to a change in outcome from May to July in non-teaching hospitals was also performed to evaluate the July effect. Results: During the study period, there were a total of 1,312,006 hospitalizations for AMI admitted in urban teaching (54.2%) or non-teaching (45.8%) hospitals in the months of May and July. Demographic characteristics were comparable between those admitted in May and July, however, May admissions had greater comorbidity and higher rates of acute multiorgan failure when compared to July admissions in teaching and non-teaching hospitals. Additionally, May AMI admissions to non-teaching hospitals had higher rates of cardiogenic shock (4.6% vs 4.3%) and cardiac arrest (5.2% vs 5.0%) compared to July admissions ( all p<0.001). July AMI admissions had lower in-hospital mortality compared to May admissions in both teaching (5.6% vs 5.8%; adjusted OR (aOR) 0.94 [95% confidence interval {CI} 0.92-0.97]; p<0.001) and non-teaching (5.9% vs 6.3%, p<0.001; aOR 0.97 [95% CI 0.95-0.99]; p=0.02) hospitals. When we analyzed the July effect using the difference-in-difference model for in-hospital mortality, we did not identify a July effect for in-hospital mortality in AMI admissions (p=0.14). Conclusions: Unlike prior reports, we did not identify a July effect for in-hospital mortality in this large contemporary AMI population in the United States. Greater care and support for new incoming trainees and/or awareness of a potential July effect among hospitals may have resulted in improved outcomes in July when compared to May.

Introduction: There are limited data on the prevalence, management and outcomes associated with concomitant aortic stenosis (AS) and acute myocardial infarction (AMI). Methods: All adult hospitalizations with a primary diagnosis of AMI were identified from the HCUP-NIS database (2000-2017). Admissions with a concomitant diagnosis of AS were compared to AMI admissions without AS. Outcomes of interest included prevalence of AS, in-hospital mortality, use of in-hospital cardiac procedures, hospitalization costs, length of stay, and discharge disposition. Results: During the study period, there were a total of 11,622,528 AMI admissions. Among these 513,688 (4.4%) were identified with concomitant AS. Adjusted temporal trends revealed an increase in prevalence of AS among STEMI (adjusted odds ratio [AOR] in 2017 vs 2000 1.15) and NSTEMI (AOR 2017 vs 2000 1.28) hospitalizations. AMI admissions with concomitant AS were on average older (78.8 ± 10.9 vs 67.1 ± 14.1), of female sex, had higher comorbidity, higher rates of NSTEMI (78.9% vs 62.1%), acute non-cardiac organ failure (13.4% vs 9.2%), and cardiogenic shock (5.1% vs 4.8%)(all p<0.001) when compared to those without AS. Concomitant AS was associated with significantly lower use of coronary angiography (45.5% vs 64.4%), percutaneous coronary intervention (20.1% vs 42.5%), coronary atherectomy (1.7% vs. 2.8%), and mechanical circulatory support (3.5% vs 4.8%) (all p <0.001), but had had higher rates of coronary artery bypass surgery and surgical aortic valve replacement (5.9% vs 0.1%) compared to those without AS. Admissions with AMI and AS had higher in-hospital mortality (9.2% vs. 6.0%; adjusted OR 1.12 [95% CI 1.10-1.13]; p <0.001). Concomitant AS was associated with longer hospital stay (median [interquartile range] 5[3-8] vs 3[2-6]), more frequent palliative care consultations (6.5% vs 2.3%), and less frequent discharges to home (44.6% vs 63.3%) when compared to AMI admissions without AS. Conclusions: In this large nationwide study, an increase in prevalence of AS in both STEMI and NSTEMI hospitalizations was noted. AMI admissions with concomitant AS had lower use of guideline-directed therapies, higher in-hospital mortality, and longer hospital stays.

Introduction: Despite well-established device selection algorithms, there remain wide variations in mechanical circulatory support (MCS) device utilization in patients with cardiogenic shock complicating acute myocardial infarction (AMI-CS). Further, there are limited national-level data on the contemporary practices of MCS device use. Methods: To evaluate national utilization patterns of MCS devices, we identified adult admissions (>18 years) with AMI-CS from the HCUP-NIS data (2005-2017). Use of MCS devices including intraaortic balloon pump (IABP), percutaneous left ventricular assist devices (pLVAD) (Impella/Tandem Heart), and extracorporeal membrane oxygenation (ECMO) during hospitalization was identified. We evaluated trends in the initial MCS device used (IABP alone, pLVAD alone, or ≥2 MCS devices), device escalation, bridging to durable LVAD/heart transplantation, and predictors of in-hospital mortality and device escalation. Results: Among a total of 327,283 AMI-CS admissions in this 13-year period, 132,146 (40.2%) had an MCS device with information on timing of placement. IABP, pLVAD, ≥2 MCS, and ECMO devices were used as initial device in 120,928 (92.0%), 8,202 (6.2%), 2,305 (1.7%), and 711 (0.1%) admissions, respectively. Most admissions were maintained on initiated MCS device with 1-1.5% being escalated (IABP to pLVAD/ECMO, pLVAD to ECMO). The median time to escalation across all devices categories was 2 (IQR 1-4) days. Urban, medium, and large-sized hospitals, and acute multiorgan failure were significant independent predictors of MCS escalation. In admissions receiving MCS, escalation of MCS device was associated with higher in-hospital mortality (adjusted OR 1.56, 95% CI 1.38-1.75; p <0.001). Admissions receiving durable LVAD/heart transplantation increased over time in those initiated on pLVAD and ≥2 MCS devices resulting in lower in-hospital mortality. Conclusions: In this 13-year study, escalation from initial MCS device was associated with higher in-hospital mortality suggestive of higher acuity of illness. However, the observed increase in number of durable LVADs or heart transplantations may be an indication of the utility of these MCS devices as successful bridge therapies.

Background: Aortic regurgitation (AR) can develop in adults with repaired coarctation of aorta (COA), but there are limited data about left ventricular (LV) remodeling and clinical outcomes in this population. The purpose of the study was to compare LV remodeling (LV mass index [LVMI], LV ejection fraction [LVEF], and septal E/e’) and onset of symptoms before aortic valve replacement (AVR), and LV reverse remodeling (%-change in LVMI, LVEF and E/e’) after AVR in patients with versus without repaired COA presenting with AR. Methods:: Asymptomatic adults with repaired COA presenting with moderate/severe AR (AR-COA group) were matched 1:2 to asymptomatic adults without COA and similar severity of AR (control group). Results: Although both groups (AR-COA n=52, and control n=104) had similar age, sex, body mass index, aortic valve gradient, and AR severity, the AR-COA group had higher LVMI (124±28 versus 102±25 g/m2, p<0.001) and E/e’ (12.3±2.3 versus 9.5±2.1, p=0.02) but similar LVEF (63±9% versus 67±10%, p=0.4). COA diagnosis (adjusted HR 1.95, 95%CI 1.49-2.37, p<0.001), older age, E/e’, and LV hypertrophy wereassociated with onset of symptoms. Of 89 patients (AR-COA n=41, and control n=48) with echocardiographic data at 1-year post-AVR, the AR-COA group had less regression of LVMI (-8% [95%CI -5 to -11] versus -17% [95%CI -15 to -21], p<0.001) and E/e’ (-5% [95% CI -3 to -7] versus -16% [95% CI -13 to -19], p<0.001). Conclusions: Patients with COA and AR had a more aggressive clinical course, and perhaps may require a different threshold for surgical intervention.

Background: Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. This study aimed to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). Methods: Retrospective study of adults with COA (n=126; age 36±16 years), that underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mmHg or LV end-diastolic pressure (LVEDP) >16 mmHg. Results: The median PAWP was 13 (11-18) mmHg, and had a good correlation with LA reservoir strain (r=-0.69, p<0.001) and LA booster strain (r=-0.61, p<0.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13, and tricuspid regurgitation velocity >2.8 m/s (p<0.05 for all). The median LVEDP was 17 (14-20) mmHg, and LVEDP had a modest correlation with LA reservoir strain (r=-0.39, p<0.001) and LA booster strain (r=-0.33, p=0.002). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13 and tricuspid regurgitation >2.8 m/s (p<0.05 for all). Conclusions: These data suggest that LA strain could be used to identify patients with increased LV filling pressure thereby improving patient selection for cardiac catheterization and interventions.

Introduction: Sudden cardiac arrest (SCA) and death (SCD) are the most serious sequelae of many genetic heart diseases (GHDs). Increased awareness of this has led to increased detection in employment screenings. For patients in high-risk jobs, premature and potentially unnecessary termination from their profession, rather than “Return-to-Work (RTW),” has become an undesired consequence of this awareness. The objective of this study is to evaluate the outcomes of patients with GHDs in high-risk professions who were allowed to RTW. Methods: We performed a retrospective review of 3,641 working-age patients referred for evaluation of a potential GHD between 6/2000-12/2021 to identify those either in or being recruited into a high-risk profession. A profession was defined as “high-risk” if it is safety-sensitive or required regular medical evaluations. Charts were reviewed for medical history, RTW decision making, and breakthrough cardiac events (BCEs). Results: Overall, 33 patients [(0.9%); 3 females (9%); mean age at diagnosis 25 ± 15 years] had been either put on hold from their high-risk job (n = 15; 45%) or disqualified as a recruit (18; 55%) prior to our evaluation due to their GHD diagnosis. This included 15 military, 10 pilots, 6 law enforcement and first responders, and 2 commercial driver license professionals and recruits. Most patients were diagnosed with Long QT syndrome (n = 23; 70%). After treatment initiation, 14 (93%) professionals and 16 (89%) recruits received physician RTW approval while 3 (9%) patients did not receive RTW approval due to disease severity and/or unwillingness to initiate treatment. Of the remaining 14 professionals that received physician RTW approval, 4 (29%) were not allowed to return to their jobs, while 14/16 recruits (88%) were not permitted to start their career. None of the RTW-approved patients had a BCE after evaluation (160.7 follow-up years). Conclusions: Patients with GHDs in high-risk professions are often terminated due to perceived SCA/SCD risk. However, within our small cohort, the risk of BCEs in optimally treated patients was low. This data suggests that the certification process of individuals in these high-risk and safety-sensitive occupations should be further examined and potentially modified.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) is associated with worse outcomes compared to sinus rhythm (SR). The prevalence of AF and its impact on outcomes in very severe AS (vsAS) is unknown. Objectives: To determine the prevalence and prognostic significance of AF in vsAS. Methods: A total of 563 patients with vsAS (transaortic valve peak velocity ≥5 m/sec) were identified retrospectively out of 3139 with aortic valve area ≤1.0 cm 2 or ≤0.6 cm 2 /m 2 and left ventricular ejection fraction (LVEF) ≥50%. Patients were divided by rhythm (AF vs SR) at the time of index transthoracic echocardiogram. Outcomes in AF versus SR were compared in propensity-matched analyses (2 SR:1 AF). Results: AF was present in 50/563 patients (9%) and SR in 513/563 (91%). In propensity-matched analyses (100 SR:50 AF), the mean age was 83.2±7.3 years, 54% were female. There was no difference in comorbidity index (p=0.84). There was no difference in AF compared to SR in aortic valve area (0.7±0.1 vs 0.7±0.1 cm 2 , p=0.94), peak velocity (5.3±0.3 vs 5.3±0.3 m/sec, p=0.32), LVEF (63±7 vs 65±7%, p=0.14) or E/e’ (23±13 vs 21±12, p=0.48), but patients with AF had larger left atrial volume index (60±16 vs 48±15 mL/m 2 , p<0.001), higher right ventricular systolic pressure (52±15 vs 41±16 mmHg, p<0.001), and higher prevalence of moderate or more tricuspid regurgitation (33% vs 5%, p<0.001) and right ventricular systolic dysfunction (23% vs 6%, p=0.003). Age-, sex-, comorbidity index-adjusted all-cause mortality was higher in AF vs SR (HR 2.33 [1.40, 3.87], p=0.001) ( Figure: Observed overall survival ). Aortic valve replacement (AVR) was associated with improved survival (HR 0.44 [0.25, 0.76], p=0.004) with no evidence of interaction of AVR and rhythm (p=0.15). Conclusion: AF was not uncommon among patients with vsAS and identified a subset of patients with vsAS at much higher risk of mortality. Whether AVR should be considered earlier in vsAS when associated with AF needs to be investigated.

Introduction: Hypertrophic cardiomyopathy (HCM) is a disease characterized by genotypic and phenotypic heterogeneity. Correct classification of genetic variation is critical for clinical interpretation. Herein, variants of uncertain significance (VUS) pose a dilemma in clinical practice, limiting physicians’ decision making and causing anguish to patients and family members. Furthermore, with increasing knowledge and changing guidelines, continuous reassessment is crucial to maintain usefulness in practice. This study sought to assess contemporary variant classification in a large cohort of patients with HCM. Methods: Retrospective analysis of all patients with HCM seen at Mayo Clinic and all patients with a variant in one of 8 genes with strong disease association for HCM were included. Genetic test reports were obtained from electronic health records along with their original variant classification assigned by either a commercial or research laboratory. Reassessment of variant pathogenicity was performed using the 2015 ACMG guideline criteria. Population frequency was obtained using Gnomad. Co-segregation presence or absence was determined by family history and co-segregation studies. Combined Annotation Dependent Depletion (CADD) was used as computational evidence of genetic deleterious effects for single nucleotide variants. Results: Between 2003 to 2019, a total of 1,782 patients underwent laboratory or commercial HCM genetic testing. Of these, 787 (44%) had positive genetic test with a variant at least 1 of the 8 genes. The original pathogenic classification was obtained for 754 patients. Of those, 430 (57%) variants where within the gene MYBPC3, 244 (32%) within MYH7 and 80 (11%) within either ACTC1, MYL2, MYL3, TINNI3, TNNT2 or TPM1. Overall, 222 patients (29%) originally had one or more variants classified as a VUS. Upon reassessment, 120 (54%) were reclassified as either pathogenic (33%), likely pathogenic (58%), benign (5%) or likely benign (3%). Conclusion: Periodic reassessment for HCM genetic variants, especially VUS, is critical for adequate patient care and management. Cascade screening could decrease patients’ uncertainty regarding their prognosis and management.