Detection of Left Ventricular Systolic Dysfunction From Electrocardiographic Images.

BACKGROUND: Left ventricular (LV) systolic dysfunction is associated with a >8-fold increased risk of heart failure and a 2-fold risk of premature death. The use of ECG signals in screening for LV systolic dysfunction is limited by their availability to clinicians. We developed a novel deep learning-based approach that can use ECG images for the screening of LV systolic dysfunction. METHODS: Using 12-lead ECGs plotted in multiple different formats, and corresponding echocardiographic data recorded within 15 days from the Yale New Haven Hospital between 2015 and 2021, we developed a convolutional neural network algorithm to detect an LV ejection fraction <40%. The model was validated within clinical settings at Yale New Haven Hospital and externally on ECG images from Cedars Sinai Medical Center in Los Angeles, CA; Lake Regional Hospital in Osage Beach, MO; Memorial Hermann Southeast Hospital in Houston, TX; and Methodist Cardiology Clinic of San Antonio, TX. In addition, it was validated in the prospective Brazilian Longitudinal Study of Adult Health. Gradient-weighted class activation mapping was used to localize class-discriminating signals on ECG images. RESULTS: Overall, 385 601 ECGs with paired echocardiograms were used for model development. The model demonstrated high discrimination across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROCs], 0.91; area under precision-recall curve [AUPRC], 0.55); and external sets of ECG images from Cedars Sinai (AUROC, 0.90 and AUPRC, 0.53), outpatient Yale New Haven Hospital clinics (AUROC, 0.94 and AUPRC, 0.77), Lake Regional Hospital (AUROC, 0.90 and AUPRC, 0.88), Memorial Hermann Southeast Hospital (AUROC, 0.91 and AUPRC 0.88), Methodist Cardiology Clinic (AUROC, 0.90 and AUPRC, 0.74), and Brazilian Longitudinal Study of Adult Health cohort (AUROC, 0.95 and AUPRC, 0.45). An ECG suggestive of LV systolic dysfunction portended >27-fold higher odds of LV systolic dysfunction on transthoracic echocardiogram (odds ratio, 27.5 [95% CI, 22.3-33.9] in the held-out set). Class-discriminative patterns localized to the anterior and anteroseptal leads (V2 and V3), corresponding to the left ventricle regardless of the ECG layout. A positive ECG screen in individuals with an LV ejection fraction ≥40% at the time of initial assessment was associated with a 3.9-fold increased risk of developing incident LV systolic dysfunction in the future (hazard ratio, 3.9 [95% CI, 3.3-4.7]; median follow-up, 3.2 years). CONCLUSIONS: We developed and externally validated a deep learning model that identifies LV systolic dysfunction from ECG images. This approach represents an automated and accessible screening strategy for LV systolic dysfunction, particularly in low-resource settings.

Substrate Mapping Alters Ventricular Tachycardia Inducibility.

BACKGROUND: Initiation of ventricular tachycardia (VT) by programmed electrical stimulation (PES) has an important role to allow mapping and assess ablation end points. We hypothesized that substrate mapping may alter VT inducibility by mechanical bumping of critical sites. METHODS: Subjects with left ventricular scar-related VT that was inducible by PES who were undergoing ablation were included. PES was repeated after substrate mapping (Group I) or after time under sedation/anesthesia during which additional imaging and transeptal puncture were performed without substrate mapping (Group II). The response to the second PES was categorized as type I if the same VT was induced, type II if a different VT was induced, and type III if VT was not inducible. RESULTS: Twenty-eight patients (median age 66 years, 61% ischemic cardiomyopathy), 14 in Group I and 14 in Group II, were included. Age, time between initial and second PES, type of cardiomyopathy, ejection fraction, and anesthesia methods were not different between the 2 groups. Initial VT cycle length, however, was shorter in Group I (305 millisecond [range, 235-600] versus 350 millisecond [range, 235-600], P=0.016). Also, Group I required more extrastimuli to induce VT in PES 1 (2 [1-4] versus 2 [1-3], P=0.022). In Group I, following substrate mapping, the second PES induced the same VT in 3 patients (21%), a different VT in 9 (64%), and no VT in 2 (14%) patients. In contrast, in Group II the same VT was induced in 10 (71%) patients, a different VT in 3 (21%) and no VT in 1 (7%) patient (P=0.017). CONCLUSIONS: Mechanical effects of substrate mapping commonly alter inducibility of VT. This has important implications for catheter ablation procedure planning and acute assessment of outcome and can potentially account for some recurrent VTs that are not recognized at the time of the procedure.

Multicenter assessment of the outcomes of subcutaneous ICD implantation in patients with prior or future sternotomy.

BACKGROUND: The subcutaneous ICD (S-ICD) is a viable alternative to transvenous ICD and avoids intravascular complications in patients without a pacing indication. The outcomes of S-ICD implantation are uncertain in patients with prior sternotomy. OBJECTIVE: We aim to compare the implant techniques and outcomes with S-ICD implantation in patients with and without prior sternotomy. METHODS: Multicenter retrospective cohort study including adult patients with an S-ICD implanted between January 2014 and June 2020. Outcomes were compared between patients with and without prior sternotomy. RESULTS: Among the 212 patients (49 ± 15 years old, 43% women, BMI 30 ± 8 kg/m2 , 68% primary prevention, 30% ischemic cardiomyopathy, LVEF median 30% IQR 25%-45%) who underwent S-ICD implantation, 47 (22%) had a prior sternotomy. There was no difference in the sensing vector (57% vs. 53% primary, p = 0.55), laterality of the S-ICD lead to the sternum (94% vs. 96% leftward, p = 0.54), or the defibrillation threshold (65 ± 1.4 J vs. 65 ± 0.8 J, p = 0.76) with versus without prior sternotomy. The frequency of 30-day complications was similar with and without prior sternotomy (n = 3/47 vs. n = 15/165, 6% vs. 9%, p = 0.56). Over a median follow-up of 28 months (IQR 10-49 months), the frequency of inappropriate shocks was similar between those with and without prior sternotomy (n = 3/47 and n = 16/165, 6% vs. 10%, p = 0.58). CONCLUSION: Implantation of an S-ICD in patients with prior sternotomy is safe with a similar risk of 30-day complications and inappropriate ICD shocks as patients without prior sternotomy.

Leak closure following left atrial appendage exclusion procedures: A multicenter registry.

BACKGROUND: Though infrequent, incomplete left atrial appendage closure (LAAC) may result from residual leaks. Percutaneous closure has been described though data is limited. METHODS: We compiled a registry from four centers of patients undergoing percutaneous closure of residual leaks following LAAC via surgical means or with the Watchman device. Leak severity was classified as none (no leak), mild (1-2 mm), moderate (3-4 mm), or severe (≥5 mm). Procedural and clinical success was defined as the elimination of leak or mild residual leak at the conclusion of the procedure or follow-up, respectively. RESULTS: Of 72 (age 72.2 ± 9.2 years; 67% male) patients, 53 had undergone prior LAAC using the Watchman device and 19 patients surgical LAAC. Mean CHADS2 -VA2 Sc score was 4.0 ± 1.8. The median leak size was 5 mm, range: 2-13). A total of 13 received Amplatzer Vascular Plug-II, 18 received Amplatzer Duct Occluder-II and 40 patients received coils. One underwent closure using a 21 mm-Watchman. Procedural success was 94%. Zero surgical and nine Watchman patients (13%) had a residual leak at procedural-end (five mild, three moderate, and one severe)-only one patient had no reduction in leak size. Overall leak size reduction was 94%. Two (3%) had intraoperative pericardial effusion. There were no device embolizations, device-related thrombi, or procedural deaths. Clinical success was maintained at 94%. Two had cerebrovascular accidents-at 2 days (transient ischemic attack) and 10 months postprocedure. Two had major bleeding outside the 30-day periprocedural window. CONCLUSION: Percutaneous closure of residual leaks following left atrial appendage closure is feasible and associated with good outcomes. The procedural risk appears to be satisfactory.

Safety and feasibility of peri-device leakage closure after LAAO: an international, multicentre collaborative study.

BACKGROUND: Residual peri-device leakage (PDL) is frequent after left atrial appendage occlusion (LAAO). Little is known about management strategies, procedural aspects and outcomes of interventional PDL closure. AIMS: The aim of this study was to assess the safety and feasibility of PDL closure after LAAO. METHODS: Fifteen centres contributed data on baseline characteristics, in-hospital and follow-up outcomes of patients who underwent PDL closure after LAAO. Outcomes of interest included acute success and complication rates and long-term efficacy of the procedure. RESULTS: A total of 95 patients were included and a cumulative number of 104 leaks were closed. The majority of PDLs were detected within 90 days (range 41-231). Detachable coils were the most frequent approach (42.3%), followed by the use of the AMPLATZER Vascular Plug II (29.8%) and the AMPLATZER Duct Occluder II (17.3%). Technical success was 100% with 94.2% of devices placed successfully within the first attempt. There were no major complications requiring surgical or transcatheter interventions. During follow-up (96 days [range 49-526]), persistent leaks were found in 18 patients (18.9%), yielding a functional success rate of 82.7%, although PDLs were significantly reduced in size (pre-leak sizemax: 6.1±3.6 mm vs post-leak sizemax: 2.5±1.3 mm, p<0.001). None of the patients had a leak >5 mm. Major adverse events during follow-up occurred in 5 patients (2 ischaemic strokes, 2 intracranial haemorrhages, and 1 major gastrointestinal bleeding). CONCLUSIONS: Several interventional techniques have become available to achieve PDL closure. They are associated with high technical and functional success and low complication rates.

Electrocardiographic recognition of benign and malignant right ventricular arrhythmias.

Ventricular arrhythmias (VAs) can originate from different anatomical locations of the right ventricle. Ventricular arrhythmias originating from right ventricle have unique electrocardiographic (ECG) characteristics that can be utilized to localize the origin of the arrhythmia. This is crucial in pre-procedural planning particularly for ablation treatments. Moreover, non-ischaemic structural heart diseases, such as infiltrative and congenital heart diseases, are associated with the VAs that exhibit particular ECG findings. This article comprehensively reviews discriminatory ECG characteristics of VAs in the right ventricle with and without structural right ventricular diseases.

The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function.

The endothelium responds to numerous chemical and mechanical factors in regulating vascular tone, blood pressure, and blood flow. The endothelial volume-regulated anion channel (VRAC) has been proposed to be mechanosensitive and thereby sense fluid flow and hydrostatic pressure to regulate vascular function. Here, we show that the leucine-rich repeat-containing protein 8a, LRRC8A (SWELL1), is required for VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial LRRC8A regulates AKT-endothelial nitric oxide synthase (eNOS) signaling under basal, stretch, and shear-flow stimulation, forms a GRB2-Cav1-eNOS signaling complex, and is required for endothelial cell alignment to laminar shear flow. Endothelium-restricted Lrrc8a KO mice develop hypertension in response to chronic angiotensin-II infusion and exhibit impaired retinal blood flow with both diffuse and focal blood vessel narrowing in the setting of type 2 diabetes (T2D). These data demonstrate that LRRC8A regulates AKT-eNOS in endothelium and is required for maintaining vascular function, particularly in the setting of T2D.

Coronary artery calcium score and risk of cardiovascular events without established coronary artery disease: a systemic review and meta-analysis.

BACKGROUND: Coronary artery calcium (CAC) is an indicator of atherosclerosis, and the CAC score is a useful noninvasive assessment of coronary artery disease. OBJECTIVE: To compare the risk of cardiovascular outcomes in patients with CAC > 0 versus CAC = 0 in asymptomatic and symptomatic population in patients without an established diagnosis of coronary artery disease. METHODS: A systematic search of electronic databases was conducted until January 2018 for any cohort study reporting cardiovascular events in patients with CAC > 0 compared with absence of CAC. RESULTS: Forty-five studies were included with 192 080 asymptomatic 32 477 symptomatic patients. At mean follow-up of 11 years, CAC > 0 was associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared to a CAC = 0 in asymptomatic arm [pooled risk ratio (RR) 4.05, 95% confidence interval (CI) 2.91-5.63, P < 0.00001, I2 = 80%] and symptomatic arm (pooled RR 6.06, 95% CI 4.23-8.68, P < 0.00001, I2 = 69%). CAC > 0 was also associated with increased risk of all-cause mortality in symptomatic population (pooled RR 7.94, 95% CI 2.61-24.17, P < 0.00001, I2 = 85%) and in asymptomatic population CAC > 0 was associated with higher all-cause mortality (pooled RR 3.23, 95% CI 2.12-4.93, P < 0.00001, I2 = 94%). In symptomatic population, revascularization in CAC > 0 was higher (pooled RR 15, 95% CI 6.66-33.80, P < 0.00001, I2 = 72) compared with CAC = 0. Additionally, CAC > 0 was associated with more revascularization in asymptomatic population (pooled RR 5.34, 95% CI 2.06-13.85, P = 0.0006, I2 = 93). In subgroup analysis of asymptomatic population by gender, CAC > 0 was associated with higher MACE (RR 6.39, 95% CI 3.39-12.84, P < 0.00001). CONCLUSION: Absence of CAC is associated with low risk of cardiovascular events compared with any CAC > 0 in both asymptomatic and symptomatic population without coronary artery disease.

Periaortic Ventricular Tachycardias in Nonischemic Cardiomyopathy: Substrate and Electrocardiographic Correlations.

BACKGROUND: Periaortic fibrotic ventricular tachycardia (VT) substrate is common in nonischemic cardiomyopathy (NICM), often intramural, and difficult to ablate. We sought to better characterize normal and abnormal periaortic voltage map parameters and NICM periaortic VTs. METHODS: In 15 patients without heart disease, the 5th percentile of endocardial voltage for increasing distance from the aortic valve ring was determined. In 53 consecutive patients with NICM (64±11 years; left ventricular ejection fraction 31±10%) undergoing ablation of recurrent VT, periaortic electrogram voltage and VT characteristics were analyzed. RESULTS: In healthy patients, the fifth percentile of the bipolar voltage increased proportional to the distance from the aortic valve ring, from 1.0 mV at 1 cm to 1.5 mV at 1.5 cm; the corresponding unipolar voltage cutoffs were 5.0 and 7.5 mV. A total of 160 VTs were induced in 53 patients with NICM, of which 28 VTs in 20 patients had periaortic origins. Periaortic VTs were associated with similar periaortic bipolar voltage, but lower UVs consistent with intramural fibrosis as an important substrate. Periaortic VTs could be divided into left and right bundle branch block forms with mapping showing right septal and lateral exits. Left bundle branch block VTs were more often acutely abolished with ablation (100% versus 69%; P=0.034), but with a 23% incidence of heart block. Greater extent of low voltage was associated with more induced VTs and worse acute outcome. CONCLUSIONS: Adjusting voltage parameters based on distance from the aortic valve may improve definition of left ventricular outflow tract arrhythmia substrate. Periaortic VTs are common in NICM, often associated with intramural substrate and can be divided into left bundle branch block and right bundle branch block types associated with different ablation outcomes and risks.

Role of diabetes and insulin use in the risk of stroke and acute myocardial infarction in patients with atrial fibrillation: A Medicare analysis.

BACKGROUND: Atrial fibrillation (AF) is associated with elevated risk for ischemic stroke and myocardial infarction (MI). The aim of the study is to assess the role of insulin use on the risk of stroke and MI in AF patients with diabetes. METHODS: We identified Medicare beneficiaries with new AF in 2011 to 2013. Primary outcomes were ischemic stroke and MI. Multivariate Cox regression models were used to assess the association between AF and time to stroke and MI. We adjusted for anticoagulant as a time-dependent covariate. RESULTS: Out of 798,592 AF patients, 53,212 (6.7%) were insulin-requiring diabetics (IRD), 250,214 (31.3%) were non-insulin requiring diabetics (NIRD) and 495,166 (62%) were non-diabetics (ND). IRD had a higher risk of stroke when compared to NIRD (adjusted HR: 1.15, 95% CI 1.10-1.21) and ND (aHR 1.24, 95% CI 1.18-1.31) (P < .01 for both). The risk of stroke was higher in NIRD compared to ND (aHR 1.08, 95% CI 1.05-1.12). For the outcome of MI, IRD had a higher risk compared to NIRD (aHR 1.24, 95% CI 1.18-1.31) and ND (aHR 1.46, 95% CI 1.38-1.54)]. NIRD had a higher risk compared to ND (aHR 1.17, 95% CI 1.13-1.22). Anticoagulation were most effective at preventing stroke in ND [0.72 (0.69-0.75)], and NIRD [0.88 (0.85-0.92)], but were not associated with significant reduction in stroke in IRD [0.96 (0.89-1.04)]. CONCLUSION: There is an incremental risk of ischemic stroke and MI from non-diabetics to non-insulin diabetics with the highest risk in insulin users. Protective effect of anticoagulation is attenuated with insulin use.

A randomized controlled study comparing community based with health facility based direct observation of treatment models on patients' satisfaction and TB treatment outcome in Nigeria.

BACKGROUND: Directly observed treatment short-course (DOTS) strategy is an effective mode of treating TB. We aimed to study the cost effectiveness and patients' satisfaction with home based direct observation of treatment (DOT), an innovative approach to community-based DOT (CBDOT) and hospital based DOT (HBDOT). METHODS: A randomized controlled trial involving 150 newly diagnosed pulmonary TB patients in four TB clinics in Ile Ife , Nigeria, was done. They were randomly assigned to receive treatment with anti TB drugs for the intensive phase administered at home by a TB worker (CBDOT) or at the hospital (HBDOT). Outcome measures were treatment completion/default rates, cost effectiveness and patients' satisfaction with care using a 13 item patients satisfaction questionnaire (PS-13) at 2 months. This trial was registered with pactr.org: number PACTR 201503001058381. RESULTS: At the end of intensive phase, 15/75 (20%) and 2/75 (3%) of patients in the HBDOT and CBDOT, respectively had defaulted from treatment, p= 0.01. Of those with pretreatment positive sputum smear, 97% (68/70) on CBDOT and 54/67 (81%) on HBDOT were sputum negative for AFB at the end of 2 months of treatment, p=0.01. The CBDOT method was associated with a higher patient satisfaction score compared with HBDOT (OR 3.1; 95% CI 1.25-7.70), p=0.001.The total cost for patients was higher in HBDOT (US$159.38) compared with the CBDOT (US$89.52). The incremental cost effectiveness ratio was US$410 per patient who completed the intensive phase treatment with CBDOT. CONCLUSIONS: CBDOT is a cost effective approach associated with better compliance to treatment and better patient satisfaction compared to HBDOT.

Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay.

OBJECTIVE: To analyze the GNRHR in patients with normosmic isolated hypogonadotropic hypogonadism (IHH) and constitutional delay of growth and puberty (CDGP). DESIGN: Molecular analysis and in vitro experiments correlated with phenotype. SETTING: Academic medical center. PATIENT(S): A total of 110 individuals with normosmic IHH (74 male patients) and 50 with CDGP. INTERVENTION(S): GNRHR coding region was amplified and sequenced. MAIN OUTCOME MEASURE(S): Novel variants were submitted to in vitro analysis. Frequency of mutations and genotype-phenotype correlation were analyzed. Microsatellite markers flanking GNRHR were examined in patients carrying the same mutation to investigate a possible founder effect. RESULT(S): Eleven IHH patients (10%) carried biallelic GNRHR mutations. In vitro analysis of novel variants (p.Y283H and p.V134G) demonstrated complete inactivation. The founder effect study revealed that Brazilian patients carrying the p.R139H mutation shared the same haplotype. Phenotypic spectrum in patients with GNRHR mutations varied from complete GnRH deficiency to partial and reversible IHH, with a relatively good genotype-phenotype correlation. One boy with CDGP was heterozygous for the p.Q106R variant, which was not considered to be pathogenic. CONCLUSION(S): GNRHR mutations are a frequent cause of congenital normosmic IHH and should be the first candidate gene for genetic screening in this condition, especially in autosomal recessive familial cases. The founder effect study suggested that the p.R139H mutation arises from a common ancestor in the Brazilian population. Finally, mutations in GNRHR do not appear to be involved in the pathogenesis of CDGP.