QRS Voltage Research Articles

Sex related cardiovascular risk is non-dichotomous: artificial intelligence enhanced electrocardiography reveals continuum of risk in females

Abstract Background Females are typically underserved in cardiovascular medicine and often considered lower risk of cardiovascular disease. The use of sex as a dichotomous variable for risk stratification fails to capture the heterogeneity of risk within each sex. Purpose We aimed to develop an artificial intelligence-enhanced ECG (AI-ECG)-derived continuous sex score that can capture the continuum of risk and sex phenotypes within each sex, with the particular goal of addressing the female disadvantage. Methods We trained a convolution neural network to identify sex using the 12-lead ECG. The derivation cohort was 1,163,401 ECGs from 189,538 subjects from a USA secondary care hospital cohort and validated inthe UK Biobank (UKB). The model outputs a continuous value from 0 to 1 for sex prediction. The AI-ECG sex discordance score is the difference between predicted sex and biological sex. Results AI-ECG accurately identified sex in both the USA cohort (AUROC 0.943 (0.942-0.943)) and UKB datasets (n = 42,386, AUROC 0.971 (0.969-0.972)). In explainability analyses we found QRS duration, T wave morphology, QT interval, heart rate and QRS voltage as the most important factors in contributing to AI-ECG sex identification. In females only but not in males, sex discordance score was associated with a covariate-adjusted increased risk of cardiovascular death in outpatients with normal ECGs from the USA cohort, (Females hazard ratio (HR) 1.64 (1.18-2.29) p = 0.003, Males HR 1.04 (0.66-1.63), p = 0.86). This pattern persisted in the UKB: Females HR 1.39 (1.08-1.78) p = 0.01, Males HR 0.97 (0.77-1.22), p = 0.80, Fig 1). In phenome-wide association studies, we found females with a higher sex score discordance were more likely to have heart failure or myocardial infarction. Covariate-adjusted cox models confirmed the association of sex score discordance with increased future heart failure (HR 1.21 (1.07-1.37) p = 0.002 and future myocardial infarction (HR 1.32 (1.11-1.56) p = 0.001). In age- and body size-adjusted analyses, females with higher sex discordance score had increased left ventricular mass, and chamber volumes as well as increased muscle mass, reduced body fat percentage (Fig 2). In a genome-wide association study of sex discordance score we identified variants adjacent to IGF1R and NDRG4 in females, which have been previously associated with LV mass and sex hormone levels (Fig 2). Conclusion We describe sex discordance score as a novel AI-ECG biomarker capable of identifying females with disproportionately elevated cardiovascular risk. Sex discordance score may help uncover potential underlying mechanisms of cardiovascular disease among females, and future clinical studies are needed to determine its potential utility in identification of females at higher risk of cardiovascular events. Rather than exacerbating biases, AI-ECG has the potential to reduce female cardiovascular health inequalities.

Prognostic value of baseline and follow-up ECG in patients with biopsy-proven fulminant myocarditis

Abstract Background Fulminant myocarditis represents a life-threatening condition with poor outcomes characterized by increased short- and long-term mortality and need for heart transplant. Treatment largely relies on mechanical support and immunosuppressive therapy guided by histologic and virology findings but reliable short-term prognostic markers guiding therapy and management are still lacking. We hypothesised that baseline and short-term ECG evolution may provide relevant easily accessible prognostic information in these patients. Purpose We sought to assess the prognostic value of baseline and short-term follow-up ECG in patients affected by fulminant myocarditis. Methods We retrospectively enrolled patients with biopsy-proven fulminant myocarditis according to current diagnostic criteria. We evaluated baseline and follow-up ECG (performed 3 to 7 days after admission) together with clinical, laboratory and histologic data. The primary endpoint was a composite of in-hospital mortality or need for urgent heart transplantation. Results We enrolled 39 patients (22/39 M, 56.4%) and a mean age of 38 years. Histology demonstrated lymphocytic myocarditis in 35/39 cases, 2 eosinophilic and 1 giant cell myocarditis, 1 sarcoidosis. All patients received vasopressor and/or inotrope therapy with 19/39 requiring mechanical circulatory support. Follow-up ECGs were performed after 4.8±1.3 days from admission. The primary endpoint was reached in 7/39 patients (17.9%) with 5 deaths and 2 urgent cardiac transplants. These patients more commonly required mechanical (85.7% vs 40.6%, p=0.044) or extracorporeal membrane oxygenator (85.7% vs 12.5%, p<0.001) support and showed higher lactate levels on admission (11.0±7.3 vs 4.2±3.1 mmol/L, p=0.001). They also more frequently had cardiac arrest as first clinical presentation (50. 0% vs 9.7%, p=0.022) and sustained ventricular tachycardia (71.4% vs 15.6%, p=0.007) in the acute phase. Patients with a worse outcome showed persistence of low voltages (< 5 mm in all peripheral leads) at follow-up ECG (100.0% vs 37.5%, p=0.003) with lower R wave amplitude in lead II (1.1±0.9 vs 4.0±2.6 mm, p=0.004), III (0.7±0.5 vs 2.5±2.2 mm, p=0.043), aVF (0.9±0.7 vs 3.0±2.0 mm, p=0.01) and V6 (3.0±2.8 vs 7.5±4.2 mm, p=0.011) and reduced S wave amplitude in V1 (2.6±3.9 vs 6.4±4.4 mm, p=0.047), V2 (3.9±3.9 vs 10.2±6.7 mm, p=0.035), V3 (3.3±3.2 vs 10.7±6.7 mm, p=0.007) leads. Low QRS voltages at baseline ECG were not associated with worse prognosis (71.4% vs 46.9%, p=0.407). No significant difference in terms of steroid (85.7% vs 78.1%, p=0.929) or other immunosuppressive (14.3% vs 31.2%, p=0.366) therapy was observed between the groups. Conclusions In patients with fulminant myocarditis, persistence of low QRS voltages at 5-day follow-up ECG is associated with adverse in-hospital outcomes. Short-term ECG evolution can identify high-risk patients requiring earlier and more intensive mechanical and pharmacological treatment.

Prediction of mortality, future arrhythmia and cardiovascular disease: an artificial intelligence-enhanced electrocardiography platform

Abstract Background Artificial intelligence-enhanced electrocardiography (AI-ECG) can be used to identify existing disease, but could additionally be used to predict occurrence of future disease and death. Purpose We developed an AI-ECG platform that predicts mortality and a wide spectrum of future arrhythmia and cardiovascular disease. Methods The AI-ECG risk estimation platform (AIRE) was developed in a dataset of 1,163,401 ECGs from 189,539 patients from a secondary care setting in the USA. Uniquely, AIRE uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves (Fig 1A). AIRE was fine-tuned to additionally predict the endpoints described below. Results AIRE accurately predicts risk of all-cause mortality (C-index 0.775 (0.773-0.776) and can differentiate prognosis in high- and low-risk subjects, even when only cardiologist-defined normal ECGs are considered (Fig 2B). Additionally, in Cox regression analyses, AIRE was superior to conventional risk factors (Fig 1B). AIRE accurately predicted future ventricular arrhythmia (c-index 0.760 (0.756-0.763)), future complete heart block (CHB) (0.809 (0.805-0.814), future atrial fibrillation (0.753 (0.751-0.756), future atherosclerotic cardiovascular disease (0.696 (0.694-0.698)) and future heart failure (0.787 (0.785-0.789)) . AIRE was superior to left ventricular ejection fraction (LVEF) in predicting risk of future ventricular arrhythmias in subjects with LVEF <50% (C-index 0.649 (0.638 – 0.660) vs 0.615 (0.603 – 0.626) p < 0.0001 ). For CHB prediction, AIRE was able to further risk stratify subjects with bifascicular block and syncope into low (1.9% 5 year CHB), intermediate (8.8%), and high risk (20.7%) groups, and could guide treatment decisions. We externally validated our findings in four diverse, transnational cohorts from Brazil and the UK, including volunteers, primary care subjects and patients with Chagas disease, and found AIRE accurately predicted all-cause mortality in all four external cohorts (Fig 2). Non-mortality endpoints were successful externally validated in the UKB. In explainability analyses, we found features of QRS morphology, low QRS voltage, poor precordial R wave progression, inverted and biphasic T waves and ST segment changes were the most significant morphological features associated with high predicted mortality (Fig 1D). Through phenome- and genome-wide association studies (GWAS), we identified candidate biological pathways including changes in cardiac structure (LV mass, LV trabeculation and left atrial size). GWAS identified variants adjacent to VGLL2, KCNQ1, CCDC91 and TBX3 which have been described in association with QT interval, biological aging and metabolic syndrome (Fig 1E). Conclusion AIRE could be used worldwide across a range of clinical contexts for risk estimation of not only mortality but a wide spectrum of future arrhythmia and cardiovascular diseases.Figure 1Figure 2

Electrocardiographic and morphological cardiac remodeling in competitive female athletes - a scoping review.

To quantitatively analyse exercise-induced cardiac remodeling (EICR) data in female athletes. This scoping review included from the databases Medline, Embase, and Google Scholar, peer-reviewed original English-language articles on female athlete-populations aged ≥18 years containing data on electrocardiography (ECG), echocardiography or cardiac magnetic resonance (CMR), and excluded athletes with cardiovascular conditions. From the extracted ECG data, we calculated prevalence percentages, and from the imaging data we compared the results with the upper reference limits of the general female population (URL). We included 31 articles comprising 4,896 female athletes, aged mean 22.2±4.6 years. On ECG (n=889), most prevalent findings were increased QRS voltages for LV hypertrophy (LVH, n=97), J-point elevation (JPE, n=108), and T-wave inversion (TWI, n=104). On echocardiography (n=4,644), we found increased mean of means BSA-indexed volumes for the LV 67.3 mL/m2 (95%CI 66.8-67.8; URL=61) and right ventricle (RV) 82.7 mL/m2 (95%CI 79.5-86.0; URL=74), while atrial volumes, septal wall thickness and LV mass were within the upper reference limits of the general population (URL). On CMR (n=309), the mean of means volumes of LA (62.0 mL/m2, 95%CI 58.8-65.2; URL=61), LV (103.4 mL/m2, 95%Ci 101.8-105.0; URL=96), and RV (105.3 mL/m2, 95%CI 103.3-110.6; URL=107.2) were >URL. Female athletes demonstrate distinct features of electrical (increased QRS voltages for LVH, JPE and TWI) and morphological EICR (biventricular dilatation). On CMR, LA was borderline dilated. Extensive studies on female athletes are needed to understand sex specific EICR.

First report of the clinical characteristics and outcomes of cardiac amyloidosis in Saudi Arabia.

Cardiac amyloidosis (CA) is a potentially fatal multisystemic disease that remains significantly underdiagnosed, particularly in the Middle East. This study aims to evaluate the prevalence and clinical characteristics of CA in a high-risk population at a tertiary centre in Saudi Arabia. This cross-sectional, retrospective, single-centre study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. We reviewed the medical records of heart failure patients seen between August 2018 and July 2022 who exhibited red flags for CA and subsequently underwent CA screening. Red flags that prompted the workup included at least two of the following factors: the presence of unilateral or bilateral carpal tunnel syndrome, a family history of transthyretin amyloid (ATTR) amyloidosis and specific electrocardiographic features (relative/absolute low QRS voltage, pseudoinfarct pattern and atrioventricular/interventricular conduction abnormalities). Echocardiographic red flags included mainly increased wall thickness (≥12mm), significant diastolic dysfunction, reduced left ventricular (LV) longitudinal function, right ventricular (RV) dysfunction and elevated right atrial (RA)/pulmonary artery (PA) pressure. Cardiac magnetic resonance (CMR) red flags included aspects similar to those in an echocardiogram as well as a subendocardial or transmural late gadolinium enhancement (LGE) pattern. These patients were assessed for CA through technetium-99m pyrophosphate ([99mTc]Tc-PYP) bone scintigraphy, serum and urine protein electrophoresis with immunofixation and a serum-free light chain assay. A total of 177 patients were screened, of which 21.0 (11.9%) patients were diagnosed with transthyretin amyloid CA (ATTR-CA) and 13 (7.3%) patients were diagnosed with light chain CA (AL-CA). Compared with patients with negative/equivocal [99mTc]Tc-PYP scans (grades 0-1), patients with positive [99mTc]Tc-PYP scans (grades 2-3) were older (78.0 vs. 68.0years, P<0.001), had higher levels of troponin (P=0.003) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.001), had a higher LV mass index (P<0.001), displayed a more depressed global longitudinal strain (GLS) (P<0.001) with a greater prevalence of a relative apical sparing pattern (P<0.001) and demonstrated a higher incidence of first-degree atrioventricular block (P=0.008) and low voltage patterns on electrocardiography (P<0.001). Patients with ATTR-CA and AL-CA were more likely to have a subendocardial or transmural LGE pattern on CMR (P<0.001) and had a significantly lower overall survival (P<0.001) when compared with other heart failure aetiologies. This is the first study to describe the clinical characteristics and outcomes of CA in the Middle East and Saudi Arabia. The prevalence of CA among screened heart failure patients here aligns with major international studies, suggesting significant underdiagnosis in the region. Therefore, larger multicentric studies and regional screening programmes are urgently needed to accurately characterize the epidemiology and outcomes of CA in the Middle East.

Natural Course of Electrocardiographic Features in Arrhythmogenic Right Ventricular Cardiomyopathy and Their Relation to Ventricular Arrhythmic Events.

Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias. Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms (P<0.001), terminal activation duration (V1) from 47 to 52 ms (P<0.001), and QTc from 419 to 432 ms (P<0.001). T-wave inversions in leads V3 to V6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HRadj][V3], 2.03 [95% CI, 1.23-3.34] and HRadj[aVF], 1.87 [95% CI, 1.13-3.08]). Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.

Early detection of low QRS voltage and its association with mortality in patients with sepsis

Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p < 0.001). Similarly, among the 160 patients who required intensive care unit admission, significantly more patients in the low QRS group died in the intensive care unit (35.9% vs. 18.2%, p = 0.021). Low QRS voltage was associated with increased hospital mortality in patients with sepsis.

Exploring low QRS voltages and QRS fragmentation in pediatric and adolescent athletes: prevalence and determinants factors

Exploring low QRS voltages and QRS fragmentation in pediatric and adolescent athletes: prevalence and determinants factors

In-vivo mapping of human polymorphic ventricular tachycardia in Brugada syndrome

Abstract Background/introduction Brugada syndrome (BrS) is associated with ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PMVT). Different mechanisms have been described for human PMVT, including epicardial drifting of rotational activity before stabilization on the apex. Purpose The aim of this study is mapping human PMVT mechanisms in BrS with ECG imaging (ECGI) in-vivo. Methods All BrS patients, were prospectively enrolled between 1992 and 2022. Inclusion criteria for the study were: 1) BrS diagnosis; 2) PMVT mapped with ECGI during thoracoscopic epicardial right ventricle outflow tract ablation. PMVT was adjudicated if a changing QRS pattern was present. Phase mapping was performed for each PMVT. All maps were imported on a dedicated software and analyzed offline. Left anterior descending coronary artery was added, based on CT scan reconstruction as a reference for the interventricular septum (in grey in Figure 1). Phase maps were performed using the Hilbert transform on detrended signals and the phases of wavefront propagation were color-coded. Rotational activity was defined as a continuous progression of phase from -π to +π around a phase singularity point. Focal activity was defined as a wavefront that appears de novo, without arising from another wavefront and spreading from its origin. Results A total of 21 BrS patients with VF were analyzed and 2 patients (9.5%) were found with PMVT. A total of 2 episodes of PMVT were mapped (one for each BrS patient) with a duration of 2.9 s and 1.3 s, respectively. Both PMVT had spontaneous initiation and termination. The mean number of rotational activities was 2.45 ± 0.07, with a mean of 2.9 ± 0.71 rotations on the apex and 0.8 ± 1.13 rotations on the septum. No other rotational activity was observed. There were 2 and 1 focal activities on the septum, respectively. No other focal activity was observed. The phase mapping of both PMVT episodes was consistent with the mechanism shown in Figure 1. In the first phase of PMVT (negative QRS) a stable rotor (white arrow) is found over ventricular apex (Figure 1, Panels A-D). In Figure 1, Panel E a septal activity appears (yellow arrow). The reduction of QRS voltage is secondary to a fusion between septal (yellow arrow) and apical (white arrow) rotational activities (Figure 1, Panels F-G). In the second phase of PMVT (positive QRS) a stable focal activity (yellow arrow) is found over the ventricular septum (Figure 1, Panels H-J). Conclusion In patients with BrS, change in the QRS pattern during PMVT is secondary to a fusion between rotational septal and apical activities.Figure 1

Prevalence and determinants of low QRS voltages and QRS fragmentation in children and adolescents undergoing sports pre-participation screening.

Low QRS voltages (LQRSV) in limb leads and QRS fragmentation (FQRS) are possible electrocardiographic signs of myocardial fibrosis and cardiomyopathy, but they are not listed in current criteria for interpreting athlete's electrocardiogram (ECG). We investigated the prevalence and determinants of LQRSV and FQRS in a cohort of young apparently healthy athletes undergoing pre-participation screening (PPS). We analysed a consecutive series of 2140 ECG obtained during PPS of young athletes (mean age 12.5 ± 2.6 years, 7-18-year-old, 49% males). The peak-to-peak QRS voltage was measured in all limb leads, and LQRSV were defined when maximum value was <0.5 mV. Fragmented QRS morphologies were grouped into five patterns. Lead aVR was not considered. Maximum peak-to-peak QRS voltage in limb leads was 1.4 ± 0.4 mV, similar between younger and older athletes, but significantly lower in females than males (1.35 ± 0.38 mV vs. 1.45 ± 0.42 mV; P < 0.001). There was a weak correlation between maximal QRS voltages and body mass index (BMI), but not with type of sport or training load. Only five (0.2%) individuals showed LQRSV. At least one fragmented QRS complex was identified in 831 (39%) individuals but excluding the rSr' pattern in V1-V2, only 10 (0.5%) showed FQRS in ≥2 contiguous leads. They were older than those without FQRS, but did not differ in terms of gender, BMI, type of sport, or training load. Low QRS voltages in limb leads and FQRS in ≥2 contiguous leads excluding V1-V2 are rare in young apparently healthy athletes and are not related to the type and intensity of sport activity. Therefore, they may require additional testing to rule out an underlying disease particularly when other abnormalities are present.

CHARACTERISATION OF THE 12–LEAD ECG IN PAEDIATRIC CARRIERS OF PLAKOPHILLIN–2 GENE VARIANTS

Abstract Background and Aim The PKP2 gene encodes the desmosomal protein Plakophilin–2, vital for cellular adhesion between cardiomyocytes. It is associated with classical Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a cardiac disorder that can cause malignant ventricular arrhythmias and sudden cardiac death in the young. The 12–lead electrocardiogram (ECG) is an important tool for diagnosis of ARVC but ECG patterns in paediatric carriers of PKP2 variants have not been previously systematically assessed. Methods The retrospective study enrolled paediatric (&amp;lt;18 years) PKP2 gene carriers referred to Great Ormond Street Hospital between 2005 and 2023. Their ECGs were analysed and compared with an age and gender–matched healthy population using paired two–tailed χ2–test. Results 28 PKP2 variant carriers (54% females) were identified, of which 2 (7%) were diagnosed with ARVC at the time of the ECG, with a mean age of 13.6 +∕– 4.8 years. These were compared to 28 healthy controls (mean age of 12.7 +/– 4.4 years). 17 carriers (60%) had low QRS voltages in the lateral leads, compared to 4 controls (16%). Fractioned QRS complexes were seen in the lateral leads in 19 (67%) and in the septal leads in 20 (71%), compared to 1 and 2 controls (3.5% and 7%, respectively). Abnormal T wave inversion (TWI) for age was found in 54% of the patients (29% in lateral leads) and flat T waves in 22 patients (78%); but these were not statistically–significantly different to controls. Conclusions Paediatric carriers of PKP2 gene variants are more likely to have low QRS voltages and QRS fractionation in the lateral and anterior leads than normal controls, but the presence of abnormally inverted or flat T waves did not discriminate between gene carriers and controls. Our findings suggest that paediatric–specific ECG features may represent early phenotypic expression of PKP2 gene variants.

DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER

Abstract Case Report A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias. Discussion Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.

EXPLORING THE 12 LEAD ECG CHARACTERISTIC OF PAEDIATRIC AND YOUNG ADULT CARRIERS OF DESMOPLAKIN GENE VARIANTS

Abstract Background and Aim The DSP gene (locus. 6p24.3) encodes desmoplakin, a quintessential desmosomal protein for cellular adhesion, particularly within cardiac tissues. DSP gene variants can cause dilated cardiomyopathy, non–dilated left ventricular cardiomyopathy (NDLVC) and arrhythmogenic righ ventricular cardiomyopathy (ARVC), cardiac conditions known to trigger malignant ventricular arrhythmias and cause sudden cardiac death in young individuals. Nevertheless, the electrocardiographic (ECG) patterns in children carrying DSP variants are underexplored. Methods A retrospective analysis was conducted involving paediatric DSP gene variant carriers (&amp;lt;/=18 years), followed at Great Ormond Street Hospital from 2006 to 2023. Their 12–lead ECGs were characterised and compared with those of an age and gender–matched healthy control group (χ2, p–value&amp;lt;0.05). Results 25 DSP carriers (64% females; 12.6±4 years) were identified [including 4 (16%) with an overt cardiomyopathy phenotype] and compared to 25 healthy matched controls (12.7±4.3years). Compared to the control group, DSP carriers exhibited a higher prevalence of low QRS voltages (72% vs 44%, p= 0.041), QRS notching (72% vs 26%, p= 0,014) and flattened T waves (72% vs 52%, p= 0,026). All 4 patients with an overt cardiomyopathy phenotype had widespread low QRS voltages and QRS fractionation, as well as flattened/inverted T waves, particularly in the inferior and lateral leads. Conclusion Predominant ECG features observed in paediatric patients with DSP gene variants included low QRS voltages, QRS notching, and flat or inverted T waves. Our findings suggest that ECG features may precede the development of an overt cardiomyopathy phenotype in children with DSP variants, but further studies with larger cohorts are needed to confirm this and to determine their prognostic significance.

EOSINOPHILIC MYOPERICARDITIS: A CASE SERIES

Abstract Background Eosinophilic myocarditis is characterized by acute myocardial inflammation due to eosinophilic tissue infiltration. Methods Diagnosis was based on laboratory tests, Echo and CMR; EMB was performed in uncertain cases. Treatment was performed according to the etiology of EM. All patients underwent regular follow–up at our Center. Results This study includes 9 patients (89% Caucasian, 78% women, mean age 48.2±13.6 years), admitted in our Center from February 2021 to November 2023. 66.67% cases occurred in the setting of eosinophilic granulomatosis with polyangiitis, 11% was secondary to B–cell lymphoblastic leukemia, and 22% were labelled as idiopathic EM. All patients presented with high eosinophil count (6133±4893/mcL), elevated CRP (57±66 mg/L) and hs–troponin I (3610±5166 ng/L) levels, and 67% cases NT–proBNP (10751±4038 ng/L) was elevated. 67% patients presented with dyspnea, 56% with chest pain, and 56% with fever. On ECG, sinus tachycardia, low QRS voltages and ST segment depression with negative T–waves were common. Thickening of the myocardial walls with reduction of GLS was seen in all cases; in 44% cases, the EF was below 50%; 56% cases had mild pericardial effusion. 1 patient had intraventricular thrombi at CMR, another one had bilateral pulmonary embolism. On CMR, all patients had areas of hypokinesia, myocardial edema, and myo–pericardial late gadolinium enhancement. EMB was performed in 5 cases, confirming the presence of intramyocardial eosinophilic infiltrates. 7 patients required CICU, and 1 needed inotrope (dobutamine) use. The patient with ALL was treated with combined chemotherapy. The other EM cases were treated with immunosuppressive therapy consisting of corticosteroids and either cyclophosphamide or rituximab or mepolizumab. All patients received cardioprotective therapy with BBs and ACE–inhibitors; in patients with pericardial involvement, colchicine was administered. All patients showed rapid clinical improvement following immunosuppressive therapy initiation, with prompt reduction of circulating eosinophils and hs–troponin I values and normalization of the ejection fraction. On CMR imaging, edema disappeared at follow–up, with LGE replacement in one case. All patients were alive and in good conditions at the last follow–up. Conclusions EM is an underdiagnosed life–threatening disease. A careful assessment of the etiology, as prompt therapy, is mandatory to achieve clinical amelioration and good mid–term prognosis.

Estimating Left Ventricular Mass from the Electrocardiogram across the Spectrum of LV Mass from Normal to Increased LV Mass in an Older Age Group.

To examine the relationship of QRS voltages and left ventricular (LV) mass across the spectrum of individuals with different LV mass. Twenty QRS voltage measurements or combinations were determined in a consecutive series of 159 adults with an ECG and echocardiogram without previous myocardial infarction, left or right bundle branch block, pre-excitation, or electronic pacemaker. The four strongest and significant correlations between QRS and LV mass were S in V4, deepest S wave in any precordial lead plus S in V4, S in V3, and S in V3 plus R in AVL times QRS duration. For men, the strength of the relationships were S in V3 (F = 33.8), deepest S wave in any precordial lead plus S V4 (F = 33.7), S in V3 plus R aVL (F = 29.9), S in V4 (F = 29.79), and deepest S in precordial leads (F = 17.9). The R wave in AVL alone did not correlate with LV mass. Criteria using the R wave in lateral precordial leads did not correlate as strongly with LV mass. For women, only S in V4 significantly correlated with LV mass. Overall, the R wave voltage in limb leads (AVL I or II) did not correlate with precordial S wave amplitudes. Univariate and multivariate analysis showed that some but not all QRS voltages correlated with each other. In multivariate analysis, using only single variables and not combination of QRS variables, the only significant relationship between QRS voltage and left ventricular mass was for men the S in V3 (p = 0.04) and for women S in V4 (p = 0.016) and R in V6 (p = 0.04). The S wave in V3 and V4 correlate most strongly with LV mass while the R wave in limb leads, including AVL, do not correlate.

A clinical case of transthyretin amyloidosis with manifestations of seronegative arthritis

A clinical case of transthyretin amyloidosis with manifestations of seronegative arthritis

Predicting extremely low body weight from 12-lead electrocardiograms using a deep neural network

Previous studies have successfully predicted overweight status by applying deep learning to 12-lead electrocardiogram (ECG); however, models for predicting underweight status remain unexplored. Here, we assessed the feasibility of deep learning in predicting extremely low body weight using 12-lead ECGs, thereby investigating the prediction rationale for highlighting the parts of ECGs that are associated with extremely low body weight. Using records of inpatients predominantly with anorexia nervosa, we trained a convolutional neural network (CNN) that inputs a 12-lead ECG and outputs a binary prediction of whether body mass index is ≤ 12.6 kg/m2. This threshold was identified in a previous study as the optimal cutoff point for predicting the onset of refeeding syndrome. The CNN model achieved an area under the receiver operating characteristic curve of 0.807 (95% confidence interval, 0.745–0.869) on the test dataset. The gradient-weighted class activation map showed that the model focused on QRS waves. A negative correlation with the prediction scores was observed for QRS voltage. These results suggest that deep learning is feasible for predicting extremely low body weight using 12-lead ECGs, and several ECG features, such as lower QRS voltage, may be associated with extremely low body weight in patients with anorexia nervosa.

Prevalence, Performance and Predictors of Electrocardiographic Left Ventricular Hypertrophy in Male Black Athletes: A Retrospective Study

Introduction QRS voltages for electrocardiographic left ventricular hypertrophy (ECG-LVH) are more prominent in Black athletes than non-Black athletes. The underlying physiological relationships of ECG-LVH in BA remain enigmatic despite their greater predisposition to arterial hypertension. Objectives To determine the frequency of eight eponymous ECG-LVH criteria in male collegiate athletes in Nigeria; To determine the diagnostic performance of the most prevalent criteria; To determine the predictors of ECG-LVH. Methods 34 (thirty-four) athletes and 49 (forty-nine) non-athletic controls with normal electrocardiograms and echocardiograms were retrospectively recruited from an existing pre-participation screening cohort. They were all normotensive, non-obese and normoglycemic, and matched for age and body mass index (BMI). Results The four most frequent criteria were Sokolow-Lyon index (67.6% vs. 36.7%; χ2 = 7.7; p = .006), Romhilt’s criterion (52.9% vs. 8.2%; χ2 = 20.6; p &lt; .001), Peguero-Lo Presti criterion (38.2% vs. 22.4%; χ2 = 2.43; p &lt; .144), and Mazzoleni’s criterion (35.3% vs. 4.1%; χ2 = 13.95; p &lt; .001). The sensitivity, specificity and accuracy of these criteria ranged between 23.8%–57.1%, 38.5%–53.9%, and 32.4%–50.0%, respectively. Athletic activity (OR = 4.49; 95% confidence interval, CI = 1.63–12.36; p = .004) and lower BMI (OR = 0.78; 95% CI = 0.63–0.97; p = .026) were independent predictors of ECG-LVH by the Sokolow-Lyon criterion. Conclusions Voltage ECG-LVH criteria all poorly predict the presence of echocardiographic LVH in young male Black athletes. However, the Sokolow-Lyon criterion seems to be associated with a benign cardio-metabolic profile in such athletes and appears hypothetically superior to other voltage criteria for identifying physiological cardiac remodeling in them. This hypothesis should be tested in future studies.

Rare c.302C>T TTR Variant Associated with Transthyretin Amyloidosis.

Background and Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin (TTR) gene. More than 140 different disease-causing variants in TTR have been reported. Only a few individuals with a rare TTR variant, c.302C>T, p.(Ala101Val) (historically known as p.(Ala81Val)), primarily associated with cardiac ATTRv, have been described. Therefore, our aim was to analyze the clinical characteristics of individuals with the identified c.302C>T TTR variant at our center. Materials and Methods: We analyzed data from individuals with ATTRv who were diagnosed and treated at Vilnius University Hospital Santaros Klinikos. ATTRv was confirmed by negative hematological analysis for monoclonal protein, positive tissue biopsy or bone scintigraphy and a pathogenic TTR variant. Results: During 2018-2021, the TTR NM_000371.3:c.302C>T, NP_000362.1:p.(Ala101Val) variant was found in one individual in a homozygous state and in three individuals in a heterozygous state. The age of onset of symptoms ranged from 44 to 74 years. The earliest onset of symptoms was in the individual with the homozygous variant. A history of carpal tunnel syndrome was identified in two individuals. On ECG, three individuals had low QRS voltage in limb leads. All individuals had elevated NT-proBNP and hsTroponine I levels on baseline laboratory tests and concentric left ventricular hypertrophy on transthoracic echocardiography. The individual with the homozygous c.302C>T TTR variant had the most pronounced polyneuropathy with tetraparesis. Other patients with the heterozygous variant had more significant amyloid cardiomyopathy. When screening family members, the c.302C>T TTR variant was identified in two phenotypically negative relatives at the ages of 33 and 47 years. Conclusions: c.302C>T is a rare TTR variant associated with ATTRv cardiomyopathy. The homozygous state of this variant was not reported before, and is associated with earlier disease onset and neurological involvement compared to the heterozygote state.

Prevalence and clinical significance of low QRS voltages in healthy individuals, athletes, and patients with cardiomyopathy: implications for sports pre-participation cardiovascular screening.

Low QRS voltages (LQRSV), defined as a QRS amplitude from peak to nadir < 0.5 mV in all limb leads, are an emerging diagnostic finding on the electrocardiogram (ECG). In healthy individuals and athletes, LQRSV are rare (2.2-4% of elite athletes, 0.5% of recreational athletes, and 0.3% of sedentary individuals). LQRSV athletes commonly show ventricular arrhythmias (VAs) on exercise, and up to 40% of those with LQRSV and VAs have late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). The prevalence of LQRSV in arrhythmogenic cardiomyopathy ranges from 17-40%, predicts left ventricular (LV) involvement, and is correlated with more extensive LGE replacement on CMR. In hypertrophic cardiomyopathy (HCM), LQRSV ranges from 0.7-11%. LQRSV-HCM patients have more segments with LGE, despite relatively smaller LV mass, suggesting a more advanced clinical stage and a worse prognosis. In dilated cardiomyopathy (DCM), LQRSV range from 6-7%, but may be higher (36%) in certain genetic forms of DCM. On a follow-up, LQRSV are independently associated with incident cardiac events, such as sudden death, sustained ventricular arrhythmia, or appropriate internal cardioverter defibrillator discharge. In cardiac amyloid, LQRSV range from 34-66% and demonstrate a negative prognostic value, with worse clinical outcomes regardless of underlying biologic, genetic, and clinical variables. In conclusion, LQRSV deserve careful consideration for exclusion of arrhythmogenic substrates in healthy individuals, athletes, and patients. While additional research is needed, it is reasonable that LQRSV should trigger clinical investigation to exclude underlying diseases at risk of life-threatening arrhythmias.