Citations

Introduction: Multiple arrhythmias including ventricular tachycardia (VT) and atrial fibrillation (AF) have been reported in patients with left ventricular noncompaction (LVNC). We sought to determine the frequency of rhythm abnormalities on Holter monitoring, and their association with all-cause mortality, in patients with LVNC. Methods: Imaging databases from 2000-2016 were reviewed to identify patients with LVNC. On transthoracic echocardiography (TTE), LVNC was defined as: end systolic noncompacted: compacted (NC:C) ratio>2 and end diastolic epicardium to trough: epicardium to peak trabeculation (X:Y) ratio<0.5. Holter monitor reports from the medical record were evaluated. VT was defined as ≥3 consecutive beats of ventricular origin. All-cause mortality was obtained from a web-based research and location service (Accurint). We used a proportional hazards model to determine associations of Holter variables with all-cause mortality. Results: Among 340 LVNC patients, Holter reports were available for 177 patients (median age 45 years, interquartile range [IQR] 33-61; 45% females). On TTE, the median NC:C ratio was 2.7 (IQR 2.4-3.2) and X:Y ratio was 0.25 (IQR 0.20-0.28). The median ejection fraction (EF) was 48% (IQR 33-58). 48 patients (27%) had at least one episode of VT (median 4 episodes, IQR 2-4). The median longest duration of VT was 5 beats (IQR 4-9) and maximum rate was 148 beats per minute (IQR: 125-169). PVC burden >5% and 20% was present in 13% and 5% of patients respectively. Patients with EF<50% were more likely to have VT (43% vs 16%, p=0.0003) and PVC burden >5% (19% vs 7%, p=0.03). AF was infrequent (N=5, all persistent). All-cause mortality was 12% over median 6.9 years of follow up (IQR: 3.6-11.3 years). Presence of VT and PVC burden on Holter monitoring were not associated with all-cause mortality (p>0.05). Among patients with VT, the number, longest duration, and fastest rate of VT episodes were not associated with all-cause mortality. Conclusions: Ventricular tachycardia on Holter monitoring is common among patients with LVNC, especially those with a reduced EF. However, the clinical significance of this finding is uncertain, and presence of VT was not associated with long term all-cause mortality.

Introduction: Loss-of-function (LOF) variants in the KCNH2 -encoded Kv11.1 potassium channel cause type 2 long QT syndrome (LQT2). To date, hundreds of KCNH2 missense variants (MVs) have been published as “disease-causative”. However, it has been suggested that 10% of rare LQTS variants in the literature may be "false positives”. Objective: To determine previously published KCNH2 variants that are likely false positives and warrant demotion to at least likely benign status. Methods: A list of all case-derived LQT2-associated MVs from six large published compendia was compiled. The frequency of each MV within the Genome Aggregation Database (gnomAD, n = 141,352 individuals) was recorded. Eight in silico variant assessment tools were used to grade each MV. Variants (n=8) absent in gnomAD but predicted “benign” by all 8 tools were considered potential false positives, despite being ultra-rare, and were characterized functionally using whole-cell patch clamp. Results: Overall, 339 KCNH2 MVs were identified among LQTS cases. Of these, 13 (4%) were seen at a minor allele frequency (MAF) > 0.0004 in gnomAD. This MAF cut-off is derived from the frequency of R176W-KCNH2, a well-established albeit weakly penetrant (i.e. < 20%) LQT2-causative MV. Variants seen at MAF > R176W-KCNH2 are unlikely to be LQT2-contributing. However, 253 MVs (75%) were absent in gnomAD. Of these, 8 (4%) MVs (I96V, G187S, A203T, P241L, H254Q, G314S, P935S, and P963T) were predicted by all 8 in silico tools to be benign and had never been characterized functionally. Patch clamp studies did not demonstrate any LOF perturbation for these 8 MVs. Conclusion: This study offers compelling evidence for the demotion from LQT2-causative status to likely benign status for 21 (6%) of the 339 previously published LQT2 MVs based either on i) gnomAD MAF unacceptably high for a 1:8000 disorder (LQT2) for 13 MVs or ii) ultra-rarity (never seen in gnomAD) but in silico variant assessment tools predicting benign impact of the amino acid substitution and in vitro functional validation studies devoid of LOF for 8 additional MVs. This meticulous “pruning” exercise must be conducted for all published variants previously implicated as the monogenic cause for LQTS in particular and all genetic heart diseases in general.

AbstractBackgroundMany patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)‐like symptoms. Although these symptoms cause significant reductions in quality of life, evidence‐based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS‐like symptoms in IBD patients with quiescent disease.MethodsWe performed a single‐center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS‐like symptoms in IBD patients.Key ResultsA total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0–82.0) 63.3 per 1000 person‐years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g.Conclusions & InferencesMood disorder and Crohn's disease were positively associated with IBS‐like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS‐like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS‐like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

ABSTRACT Objective: To study the applicability of on-table extubation (OTE) protocol following congenital cardiac surgery in a low-resource setting and its impact on the length of intensive care unit (ICU) stay, hospital stay, hospitalization cost, parental anxiety, and nurse anxiety. Materials and Methods: In this prospective, nonrandomized, observational single-center study, we included all children above 1 year of age undergoing congenital cardiac surgery. We evaluated them for the feasibility of OTE using a prespecified protocol following separation from cardiopulmonary bypass. The data were prospectively collected on 60 children more than 1 year of age, belonging to the Risk Adjustment for Congenital Heart Surgery 1, 2, 3, and 4 groups and divided into two groups: those who underwent successful OTE and those who were ventilated for any duration postoperatively (30 children in each group). Duration of hospital stay, ICU stay, and total hospital cost were collected. Anxiety levels of the primary caregiver (nurse) in the ICU and the mother were assessed immediately after the arrival of the child in the ICU using the State Trait Anxiety Inventory (STAI). Results: Children who were extubated immediately following congenital cardiac surgery had significantly shorter ICU stay (median 20 [19, 22] h vs. 22 [20, 43] h [ P < 0.05]). Patients extubated on table had a significant reduction in hospital cost {median Rs. 161,000 (138,330; 211,900), approximately USD 1970 ( P < 0.05)} when compared to children who were ventilated postoperatively {median Rs. 201,422 (151,211; 211,900) , approximately USD 2464}. The anxiety level in mothers was significantly less when their child was extubated in the operating room (STAI 36.5 ± 5.4 vs. 47.4 ± 7.4, P < 0.001). However, for the same subset of patients, anxiety level was significantly higher in the ICU nurse (STAI 46.0 ± 5.6 vs. 37.8 ± 4.1, P < 0.05). Conclusion: OTE following congenital cardiac surgery is associated with a shorter duration of ICU stay and hospital stay. It also reduces the total hospital cost and the anxiety level in mothers of children undergoing congenital heart surgery. However, the primary bedside caregiver during the child’s ICU stay had increased anxiety managing patients with OTE.

Introduction: Atrial fibrillation (AF) is a serious complication, which occurs in 30% to 40% of patients after surgical aortic valve replacement (SAVR) and contributes to adverse outcomes. Advanced technology has enabled transcatheter aortic valve replacement (TAVR) in patients with High-risk Severe Aortic Stenosis (HRSAS). In these patients, the compliance of the systemic vasculature is an independent predictor of diastolic dysfunction, a known predictor of postoperative AF (POAF). We hypothesize that patients with HRSAS undergoing TAVR represent a population at increased risk for POAF. METHODS: The medical records of 195 TAVR patients at the Mayo Clinic from November 2008 to January 2013 were analyzed. All patient demographic, clinical, pre- and post-procedural outcomes were collected from the patients’ medical records, and reviewed to ascertain all cases of POAF (AF ≤30 days of surgery). Patients with a prior history of AF (n= 75 (38.5%)) were excluded. Logistic regression analysis was used to identify clinical predictors of POAF after TAVR. Results: The mean age of the study population was 80.8±7.8 years and 60.8% (n=73) were men. The mean STS risk score was 8.9±5.1. Of the 120 patients without prior AF, 20.8% (n=25) developed new-onset POAF after TAVR. Patients who developed POAF were more likely to have undergone a transapical or transaortic TAVR approach (OR 3.20; 95% CI (1.3-8.0), had a higher incidence of renal complications (52.0% vs 21.5%; p= 0.003), greater hospital length of stay (7.4±2.58 vs 5.0±2.6 days; p= 0.0003, and a trend toward higher 30-day mortality (28.0% vs 13.7%; p= 0.09) and pulmonary complications (16.0% vs 5.4%; p= 0.08) compared with those who did not develop POAF, respectively. Neurologic complications were not different between the 2 group (4.0% vs 3.2%; p= 0.85). Conclusions: Patients with High-risk Severe Aortic Stenosis undergoing TAVR have increased risk of POAF, primarily associated with a transapical or aortic surgical approach. Patients who develop POAF had higher incidence of post-procedural complications and longer hospitalizations. Therefore, perioperative strategies aimed at prevention of POAF are as important in TAVR patients as in those undergoing SAVR.

Introduction: Aldosterone (Aldo) increases sodium and water reabsorption and mediates inflammatory processes. Its relationship to co-morbidities has not been well defined in the general population. Hypothesis: We addressed the hypothesis that plasma aldosterone concentration (PAC) is associated with metabolic and cardiorenal diseases in the general community. Methods: We determined PAC in a general community-based cohort from Olmsted County, MN (n=1,674), and defined correlations with cardiorenal, metabolic diseases and myocardial function and structure. Results: PAC was detected in all subjects and ranged from 2.5 to 91 ng/dl (mean value 6.7 ng/dl, +/- SD 6.6). Multivariate analysis adjusted for age, gender, BMI, ANP and BNP showed highly significant correlations between PAC and hypertension (HTN) (p<.0001, OR=2.28, CI:1.91-2.71), atrial fibrillation (p<.01), chronic kidney disease (CKD) (p<.0001, OR=1.64, CI:1.33-2.02), central obesity (p<.0001, OR=1.61, CI:1.27-2.05), hypertriglyceridemia (p<.003), prevalence of metabolic syndrome (MetS) (p<.0007, OR=1.40, CI=1.15-1.71), obesity (p<.0001, OR=1.48, CI:1.27-1.73), and concentric left ventricular hypertrophy (cLVH) (p=.01). Recognizing that ANP and BNP are known inhibitors of Aldo, we defined the relationship between these cardiac hormones (NTpro-ANP and NT-proBNP) and PAC and observed highly significant inverse relationships with NTpro-ANP (p=0.0009), NTpro-BNP (p=0.0003) in the general population. Conclusions: In conclusion, in the general community, PAC is strongly correlated with renal, metabolic and cardiovascular diseases as well as cardiac remodeling. Specifically, increasing PAC is strongly associated with HTN, CKD, obesity, MetS, cLVH, and lower levels of natriuretic peptides. Our data suggest a key role of Aldo as a possible biomarker and/or mediator of human cardiorenal and metabolic diseases even in the general adult population, prior to overt disease. This study also supports a possible counter regulatory relationship between cardiac natriuretic peptides and PAC. Further studies are warranted to evaluate possible therapeutic interventions targeting Aldo as a strategy to delay disease progression.

Background: Patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR) undergo aortoiliac computed tomographic angiography (CTA) of the chest/abdomen/pelvis. Despite the increasing number of TAVR procedures worldwide, little is known regarding the clinical significance of non-cardiovascular incidental findings (IFs) on TAVR-CTA scans. Objective: To determine the frequency, clinical significance and impact on survival of non-cardiovascular IFs detected on TAVR-CTA scans. Methods: CTA studies for 424 consecutive patients being evaluated for TAVR were reviewed for non-cardiovascular IFs (62% male, median age 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival. Results: An IF was present in nearly all patients (99%). The mean number of IFs per patient was 5.3 (±2.8; range 0-14). After excluding obviously benign IFs, 67% had at least one potentially pathologic IF (mean 1.1±1.0). Factors associated with higher numbers of IFs were age (p<0.0001) and use of IV contrast (p=0.03). IFs prompted clinical work-up in 39 patients (9.2%) and delayed or cancelled procedures in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of IFs was predictive of poor overall survival before (HR 1.09; 95% CI (1.02 to 1.70), p=0.02) and after adjustment for baseline clinical variables (HR 1.07; (1.0 to 1.15); p=0.04). Conclusions: This investigation demonstrates that IFs are present in nearly all TAVR-CTA scans, commonly require further clinical evaluation, and are associated with poorer survival. TAVR institutions should have mechanisms in place to ensure communication and follow-up of IFs.

Background: Randomized clinical trials are often criticized for not reflecting real-world practice. To understand the effect of site and patient selection on trial generalizability, we examined US patient and hospital participation within the Dual Antiplatelet Therapy (DAPT) Study, a broadly inclusive trial of PCI patients, using a linked analysis with the CathPCI Registry®. Methods: Within the CathPCI Registry, we identified patients undergoing PCI between September 1, 2009 and July 1, 2011 - the period of DAPT Study enrollment. We compared US patients enrolled in DAPT to CathPCI Registry patients meeting DAPT inclusion criteria. Characteristics of US DAPT sites were also compared to those of hospitals not participating in DAPT. Standardized differences (%) for all variables were estimated, with those greater than 10% considered significant. Results: Among 1,139,932 NCDR patients undergoing PCI, 748374 (65.7%) met the enrollment criteria for DAPT, and 23495 (2.1%) were enrolled. Enrolled patients were younger and had lower rates of prior stroke, CHF and peripheral vascular disease, but were similar with respect to race and gender compared with eligible patients (Table). Of the 1276 hospitals within the NCDR, 309 (24.2%) participated in DAPT. Hospital characteristics differed markedly, with DAPT-participating hospitals being larger (mean beds 468 vs. 311), more often located in urban settings (61.2% vs. 42.6%), more often affiliated with training programs (53.7% vs. 34.1%), and with higher annual PCI volumes (mean annual hospital volume 858 vs. 378 PCIs) compared with non-DAPT hospitals. Conclusions: While liberal inclusion criteria may allow randomized trials to better simulate “real-world” clinical practice, the process of site selection may encourage participation of higher volume, urban hospital settings. These findings are relevant to clinical trial interpretation and implementation of evidence-based practice throughout the healthcare system.

Background: Bystander CPR (BCPR) strongly influences survival from OHCA yet is provided in a minority of cases. The AHA has promulgated guidelines on provision of pre-arrival Hands-Only dispatcher-assisted telephone CPR (TCPR) instructions to increase the proportion of arrests receiving early BCPR; however, the impact of those guidelines is unknown. Objective: Evaluate the impact of implementing the TCPR guidelines on: recognition of OHCA by 911 dispatchers, time from call receipt to start of TCPR instructions, time to first chest compression (CC), prehospital ROSC, survival, and favorable neuro outcome (FNO). Methods: Dispatch audio records of OHCA in 3 large dispatch centers in Arizona (10/10-3/13) were reviewed using a standardized time-stamp methodology. Data were entered into a structured TCPR database linked to EMS and hospital outcome data. Intervention: Implementation of a 3.5-hour staff training and a guideline-based change in dispatch protocol. Results: There were 860 pre-implementation (P1) and 799 post-implementation (P2) cases. A total of 1265 cases met inclusion criteria. Outcome data collection and linkage is ongoing: ROSC, survival and neuro outcomes were available in 26%, 24% and 22% of cases, respectively. The proportion of cases receiving TCPR increased: P1 (28.7%); P2 (49.9%, p<0.001). Median time to beginning TCPR instructions decreased significantly: P1 (153 sec); P2 (129 sec, p<0.001) as did median time to first CC: P1 (198 sec); P2 (162 sec, p<0.001). Outcomes - see Table. Conclusion: The implementation of the AHA pre-arrival TCPR guidelines was associated with a significant improvement in the time-to-CPR instructions and time-to-first CCs and rate of provision of telephone-assisted bystander CPR. This small, preliminary analysis of prehospital ROSC, survival, and FNO revealed higher, but statistically non-significant, rates after the interventions.