Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced electrocardiogram analysis.

AIMS: Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. The ECG is used as the gatekeeper to cardiac imaging for diagnosis. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM. METHODS AND RESULTS: Advanced ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM [n = 75 overt, n = 32 relative (<15 mm hypertrophy); a subgroup of which underwent cardiovascular magnetic resonance (n = 92)], and comparator subjects (n = 2449), including healthy volunteers (n = 1672), patients with coronary artery disease (n = 372), left ventricular electrical remodelling (n = 108), ischaemic (n = 114) or non-ischaemic cardiomyopathy (n = 57), and asymmetrical septal hypertrophy HCM (n = 126). Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy [area under the receiver operating characteristic (AUC) curve (bootstrapped 95% confidence interval) 0.982 (0.965-0.993)]. Linear discriminant analysis also diagnosed ApHCM with high accuracy [AUC 0.989 (0.986-0.991)]. CONCLUSION: Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting that future diagnostic and management strategies may incorporate both features.

Electrocardiographic parameters associated with pacemaker induced cardiomyopathy.

BACKGROUND: Chronic right ventricular (RV) pacing can induce left ventricular (LV) dyssynchrony and cause pacemaker induced cardiomyopathy (PiCM). Identifying which patients are at risk for PiCM is limited. METHODS: Patients receiving RV-only permanent pacemakers (PPMs) at Duke University Medical Center between 2011 and 2017 who had normal baseline ejection fractions (EFs) were identified. Patients who developed a subsequent decrease in EF, died, or underwent cardiac resynchronization therapy, left ventricular assist device, or heart transplant without a competing cause were considered as the primary endpoint. Pre-PPM and post-PPM electrocardiograms (ECGs) were analyzed to extract scalar measurements including the lead one ratio (LOR) as well as advanced-ECG (A-ECG) features to identify predictors of PiCM. Traditional and penalized Cox regression were used to identify variables predictive of the primary endpoint. RESULTS: Pre-PPM ECGs were evaluated for 404 patients of whom 140 (35%) experienced the primary endpoint. Predictors included female sex (hazard ratio [HR] 1.14), a T' wave in V6 (HR 1.31), a P' wave in aVL (HR 0.88), and estimated glomerular filtration rate (HR 0.88). Post-PPM ECGs were evaluated for 228 patients for whom 94 (41%) experienced the primary endpoint. Predictors included female sex (HR 0.50), age (HR 1.06), and a history of congestive heart failure (HR 1.63). Neither LOR nor A-ECG parameters were strong predictors of the primary endpoint. CONCLUSIONS: Baseline and paced ECG data provide limited insight into which patients are at high risk for developing PiCM.

Heat Shock Protein 27 Levels Predict Myocardial Inhomogeneities in Hemodialysis Patients.

Background: Sudden cardiac death (SCD) is the single major cause of death in hemodialysis (HD) patients. QRS-T angle is an established marker of global repolarization heterogeneity associated with electrical instability and SCD. Heat shock protein 27 (HSP27) plays an important, protective role against noxious factors in the cardiovascular (CV) system. This study is aimed at assessing whether low HSP27 is associated with myocardial inhomogeneities in HD patients, as expressed by increases in the spatial QRS-T angle. Methods: Clinical data and biochemical, echocardiographic, and electrocardiographic parameters were evaluated in 182 HD patients. Patients were split into normal and abnormal QRS-T angle groups. Results: Patients with abnormally high QRS-T angles were older and had higher prevalence of diabetes as well as myocardial infarction, higher left ventricular mass index (LVMI) and C-reactive protein, worse oxidant/antioxidant status, and lower ejection fraction and HSP27. Multiple regression analysis revealed that abnormal QRS-T values were independently, negatively associated with serum HSP27 and positively associated with LVMI. Conclusions: Low HSP27 levels are associated with increased heterogeneity of myocardial action potential, as expressed by increased spatial QRS-T angle.

Predicting peri-operative troponin elevation by advanced electrocardiography.

BACKGROUND: Peri-operative mortality remains a global problem and an improved pre-operative risk assessment identifying those at highest risk for peri-operative myocardial injury might improve postsurgical outcomes. AIMS: To determine whether pre-operative measures of advanced electrocardiography (A-ECG) could predict elevated serum troponin T (TnT) in patients undergoing elective, major non-cardiac surgery. MATERIAL AND METHODS: This observational cohort study included 257 surgical patients who underwent elective major non-cardiac surgery between the years 2012-2013 and 2015-2016 at Karolinska University Hospital. All selected patients were ≥ 18 years of age [median age 70 (63-75) years], had a pre-operative digital 12­lead ECG < 6 months prior to the procedure and a postoperative high-sensitivity cardiac TnT (hs-cTnT) sample. A-ECG confounders including atrial fibrillation or flutter, abundant premature atrial or ventricular contractions, bundle branch blocks, QRS duration >110 ms, heart rate > 100 beats/min and paced rhythms were excluded. Previously validated A-ECG diagnostic scores that detect cardiovascular pathologies were calculated and compared in patients with and without peri-operative myocardial injury, defined as hs-cTnT >14 ng l-1. RESULTS: Pre-operative left ventricular systolic dysfunction by A-ECG was more probable in patients with than without peri-operative myocardial injury (p = 0.03). CONCLUSIONS: While a pre-operative A-ECG score for LVSD was able to differentiate between patients with versus without elevated peri-operative TnT levels, it did not add any further utility to standard clinical parameters for predicting troponin-related events in the studied population.

Substantial prevalence of subclinical cardiovascular diseases in patients with hemophilia A evaluated by advanced electrocardiography.

BACKGROUND: Patients with hemophilia A (PWHA) have reportedly lower mortality due to cardiovascular disease (CVD) compared to the general population. AIM: To evaluate signs of CVD in asymptomatic PWHA using advanced electrocardiography (A-ECG). METHODS: PWHA (n = 29, median [interquartile range] age 57 [47-70] years) and age-matched male controls (n = 29, 59 [48-68] years) were evaluated. Digital resting 12­lead ECGs were retrospectively analysed using both conventional and A-ECG techniques including derived vectorcardiography and waveform complexity. Previously validated multivariate A-ECG scores designed to detect: 1) cardiac disease in general, 2) left ventricular systolic dysfunction (LVSD), 3) coronary artery disease or coronary microvascular disease (CAD/CMVD), or 4) left ventricular hypertrophy defined as left ventricular electrical remodelling (LVH/LVER), were quantified and compared between PWHA and controls. RESULTS: Compared to controls, PWHA had a higher probability of having cardiac disease (median [interquartile range] 84.6 [32.5-99.5] vs. 0.6 [0.2-8.2]%), LVSD (4.1 [1.3-12.9] vs. 0.9 [0.5-3.2]%), CAD/CMVD (84.3 [35.6-96.6] vs. 6.7 [0.8-24.4]%), and LVH/LVER (17 [5/29] vs. 0 [0/29]%). Compared to patients with non-severe HA (n = 20), patients with severe HA (n = 9) showed a non-significant trend towards lower probability of cardiac disease, CAD/CMVD, LVSD and LVH/LVER. CONCLUSION: In PWHA, A-ECG exhibits changes more indicative of overt or subclinical CVD compared to controls, and there is a tendency for lower scores for CVD in patients with severe compared to non-severe HA. These results suggest that PWHA ≥ 40 years could be at higher risk for CVD than age-matched controls and that A-ECG could potentially be used for early detection.

The electrical determinants of increased wall thickness and mass in left ventricular hypertrophy.

INTRODUCTION: Left ventricular hypertrophy (LVH), defined as an increased left ventricular mass (LVM), can manifest as increased wall thickness, ventricular dilatation, or both. Existing LVH criteria from the electrocardiogram (ECG) have poor sensitivity. However, it is unknown whether changes in wall thickness and mass, respectively, can be separately detected by the ECG. METHODS: Patients undergoing cardiovascular magnetic resonance and resting 12-lead ECG were included. Exclusion criteria were clinical confounders that might influence the ECG, including myocardial scar. Advanced ECG (A-ECG) analysis included conventional ECG measures and amplitudes, derived vectorcardiographic and polarcardiographic measures, and singular value decomposition of waveform complexity. A-ECG scores for 1) increased LVM index (LVMI), and 2) increased global wall thickness index (GTI) beyond the upper limit of normal in healthy volunteers, respectively, were derived using multivariable logistic regression. The area under the curve (AUC) and its bootstrapped confidence interval (CI) for each score were compared to those of conventional ECG-LVH criteria including Cornell voltage, Cornell product, and Sokolow-Lyon voltage criteria. RESULTS: Out of 485 patients (median [interquartile range] age 51 [38-61] years, 54% female), 51 (11%) had increased LVMI and 65 (13%) had increased GTI. The A-ECG scores for increased LVMI (AUC [95% CI] 0.84 [0.78-0.90]), and increased GTI (0.80 [0.74-0.85]) differed, and had a higher AUC than the conventional ECG-LVH criteria (p < 0.001 for all). CONCLUSIONS: Increased LVMI differed from increased GTI in its electrocardiographic manifestation by A-ECG. New A-ECG scores outperform conventional ECG criteria for LVH in determining increased LVMI and GTI, respectively.

Successful Combination of Landiolol and Levosimendan in Patients with Decompensated Heart Failure.

Tachycardia and supraventricular tachyarrhythmias often impair cardiovascular capacity in patients with decompensated heart failure (dHF) treated with inotropes. Normalization of heart rhythm or rate typically improves diastolic filling and stroke volume (SV). Thus, isochronal administration of an ultra-short-acting and highly selective ß1-blockers, such as landiolol, along with inotropic calcium-sensitizer medications, such as levosimendan, could benefit patients with dHF.We present a case series of three patients with severe dHF and low ejection fraction who were successfully treated with a combination of landiolol and levosimendan. The co-administration of landiolol and levosimendan was well tolerated, improved cardiac function, normalized SV, and enabled the reduction of norepinephrine dosing in all patients. Additionally, the combination improved the vectorcardiographic spatial QRS-T angle and decreased the corrected QT interval. All patients were successfully discharged from the intensive care unit (ICU).A combination of levosimendan and landiolol was safe and well-tolerated. This combination may be a new option for successful treatment of patients with acute dHF complicated by sinus or supraventricular tachycardias.

Changes in spatial QRS-T angle and QTc interval in patients with traumatic brain injury with or without intra-abdominal hypertension.

Introduction: Traumatic brain injury (TBI) affects cardiac electrical function, and several extra-cerebral factors, including intra-abdominal pressure (IAP), might further modulate this brain-heart interaction. The purpose of this study was to investigate the impact of TBI, and of increased IAP during TBI, on cardiac electrical function as measured by vectorcardiographic (VCG) variables. Methods: Survival, IAP and changes in VCG variables including spatial QRS-T angle and QTc interval were measured in consecutive adult patients with either isolated TBI (iTBI), or with TBI accompanied by polytrauma to the abdomen and/or limbs (pTBI). For all patients, observations were performed just after the admission to the ICU (baseline) and at 24, 48, 72 and 96 h after admission. Results: 74 patients aged 45 ± 18 were studied. 44 were treated for iTBI and 30 for pTBI. In all patients, spatial QRS-T angle and QTc interval increased after TBI (p < 0.001), relatively more so in patients with pTBI. Compared to survivors, non-survivors also ultimately had greater widening of the spatial QRS-T angle (p < 0.001), most notably just before foraminal herniation. Wider spatial QRS-T angle and longer QTc interval were also noted in patients with IAP > 12 mmHg (p < 0.001), and with right compared to left hemispheric injury (p < 0.001). ST segment level at the J point decreased 24 and 48 h after TBI in leads I, II, III, aVR, aVF, V1, V2, V3 and V6, and increased in lead V1, especially in non-survivors. Conclusions: Spatial QRS-T angle and QTc interval increase after TBI. If foraminal herniation complicates TBI, further widening of the spatial QRS-T angle typically precedes it, followed by notable narrowing thereafter. Increased IAP also intensifies TBI-associated increases in spatial QRS-T angle and QTc interval.

ECG-derived spatial QRS-T angle is strongly associated with hypertrophic cardiomyopathy.

INTRODUCTION: ECG-derived vectorcardiography (VCG) has diagnostic and prognostic value in various diseases. Hypertrophic cardiomyopathy (HCM), a genetic disease with unexplained left ventricular hypertrophy, is one of the most common causes of sudden cardiac death (SCD) in young persons. Genotype positive status is associated with increased risk of systolic dysfunction, heart failure, and (SCD). Herein, we aimed to determine the diagnostic utility of derived VCG parameters in a large cohort of genotyped HCM patients. METHODS: Between 1997 and 2007, genetic testing was performed on 1053 unrelated patients with HCM. Of these, 967 had 12-lead ECGs suitable for computerized derivation of VCG parameters, including the spatial mean and peaks QRS-T angles, spatial ventricular gradient (SVG), spatial QRS, QT, and Tpeak-Tend (TpTe) intervals. ECGs were also evaluated using Seattle ECG criteria. Differences between HCM patients and healthy controls as well as between genotype positive versus genotype negative HCM patients were assessed. RESULTS: Spatial peaks (129.3±26.4 vs.30.5±24.2 degrees) and spatial mean QRS-T angles (121.8±38.6 vs. 47.3±27.6 degrees) were significantly higher in patients with HCM than in controls (P<0.001). The spatial peaks and mean QRS-T angles identified 94% and 84% of HCM patients, respectively, while Seattle criteria identified 70.7% of patients (P<0.001). Genotype positive patients had higher spatial mean QRS-T angles, spatial TpTe (P<0.001 respectively), spatial peaks QRS-T angles (P=0.017) and lower SVG (P<0.001) than genotype negative patients. CONCLUSIONS: ECG-derived spatial QRS-T angles can differentiate patients with HCM from controls and could provide a better tool than traditional Seattle criteria. Clinical usefulness of VCG to differentiate genotype-negative from genotype-positive patients has yet to be established.

Intra-abdominal hypertension increases spatial QRS-T angle and elevates ST-segment J-point in healthy women undergoing laparoscopic surgery.

BACKGROUND: Intra-abdominal hypertension (IAH) impairs cardiovascular function, however an effect of IAH on cardiac electrophysiology has been poorly documented. The aim of this study was to evaluate the effect of IAH following pneumoperitoneum on vectorcardiographic variables reflecting cardiac repolarisation and depolarisation. METHODS: Otherwise healthy women undergoing elective gynaecological laparoscopy were studied. Intra-abdominal pressure (IAP), spatial QRS-T angle and ST-segment J-point (STJ) were observed during surgery and the early postoperative period. RESULTS: Forty women, ages 22 to 43 were examined. Induction of IAH to 15mmHg significantly widened the spatial QRS-T angle, whereas the Trendelenburg position subsequently reduced this widening. IAH also increased STJ voltage in leads III, aVF, V2 and V3 during surgery, with increased STJ voltage persisting in several leads through the morning of postoperative day 1. CONCLUSION: Induction of IAH impacts the relationship between cardiac depolarisation and repolarisation and increases spatial QRS-T angle and STJ voltage.

The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy.

The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed.

Delineation of QRS offset by instantaneous changes in ECG vector angle can improve detection of acute inferior myocardial infarctions.

We developed an automated new method for determining QRS offset, based on angular velocity (AV) changes around the QRS loop, and compared the method's performance to that of manual and more established automated methods for determining QRS offset in both healthy subjects and patients with acute myocardial infarction (AMI). Specifically, using Frank leads reconstructed from standard 12-lead ECGs, we determined AV in the direction of change raised to the 4th power, d(t). We found that the d(t)-determined AV transition (ΔAV) nearly coincided with manually determined QRS offset in healthy subjects, and in 27 patients with anterior AMI. However, in 31 patients with inferior AMI, ΔAV typically preceded that of QRS offset determined by the established automated methods, and by more than 10ms in 32% of cases. While this "ΔAV precedence" coincided with diagnostic ST elevation in only a minority of patients with recent inferior AMI, the use of ΔAV precedence as a complement to traditional determination of ST elevation increased the sensitivity for detecting inferior AMIs from 23 to 42%.

Peripheral microvascular function is altered in young individuals at risk for hypertrophic cardiomyopathy and correlates with myocardial diastolic function.

Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in the young. Based on previous reports of functional abnormalities in not only coronary but also peripheral vessels in adults with HCM, we aimed to assess both peripheral vascular and myocardial diastolic function in young individuals with an early stage of HCM and in individuals at risk for HCM. Children, adolescents, and young adults (mean age: 12 yr) with a family history of HCM who either had (HCM group; n = 36) or did not have (HCM-risk group; n = 30) echocardiography-documented left ventricular (LV) hypertrophy as well as healthy matched controls (n = 85) and healthy young athletes (n = 12) were included in the study. All underwent assessment with 12-lead electrocardiography, two-dimensional echocardiography, tissue Doppler imaging and laser Doppler with transdermal iontophoresis of ACh and sodium nitroprusside. LV thickness and mass were increased in HCM and athlete groups compared with control and HCM-risk groups. The mitral E-to-e' ratio, measured via tissue Doppler, was increased in HCM (P < 0.0001) and HCM-risk (P < 0.01) groups compared with control and athlete groups, as were microvascular responses to ACh (HCM group: P = 0.045 and HCM-risk group: P = 0.02). Responses to ACh correlated with the E-to-e' ratio (r = 0.5, P = 0.001). Microvascular responses to sodium nitroprusside were similar in all groups (P > 0.2). HCM-causing mutations or its familial history are associated with changes in cardiac diastolic function and peripheral microvascular function even before the onset of myocardial hypertrophy. Tissue Doppler can be used to differentiate HCM from physiological LV hypertrophy in young athletes.

The prognostic value of positive T-wave in lead aVR in hemodialysis patients.

BACKGROUND: Given that cardiac disease is the leading cause of mortality in hemodialysis (HD) patients, identification of patients at risk for cardiac mortality is crucial. The aim of this study was to determine if positive T-wave amplitude in lead aVR (TaVR) was predictive of cardiovascular (CV) mortality and sudden cardiac death (SCD) in a group of HD patients. METHODS AND RESULTS: After exclusion, 223 HD patients were prospectively followed-up for 25.43 ± 3.56 months. Patients were divided into TaVR negative (n = 186) and TaVR positive (n = 37) groups. Myocardial infarction, diabetes and beta-blocker therapy were more frequent in positive TaVR patients. Patients with upright TaVR were older, had higher left ventricular mass index, lower ejection fraction, higher calcium × phosphate product, higher troponin T level, higher prevalence of ST-T abnormalities, and increased width of QRS complex and QT interval, compared with patients with negative TaVR. A Kaplan-Meier analysis showed that the cumulative incidences of CV mortality as well as SCD were higher in patients with positive TaVR compared with those with negative TaVR (log-rank, p < 0.001 in both cases). A multivariate analysis selected age [hazard ratio (HR) 1.71, p < 0.001], heart rate (HR 1.42, p = 0.016), and positive TaVR (HR 2.21, p = 0.001) as well as age (HR 1.88, p < 0.001), and positive TaVR (HR 1.53, p = 0.014) as independent predictors of CV mortality and SCD, respectively. CONCLUSION: In HD patients, positive TaVR is an independent and powerful predictor of CV mortality as well as SCD. This simple ECG parameter provides additional information beyond what is available with other known traditional risk factors and allows the identification of patients most at risk of CV events.

High resolution ECG-aided early prognostic model for comatose survivors of out of hospital cardiac arrest.

Out of hospital cardiac arrest (OHCA) has a high mortality despite modern treatment. Reliable early prognosis in OHCA could significantly improve clinical decision making. We explored prognostic utility of advanced ECG parameters, obtained from high-resolution ECG, in combination with clinical and OHCA-related parameters during treatment with mild induced hypothermia (MIH) and after rewarming in unconscious survivors of OHCA. Ninety-two patients during MIH and 66 after rewarming were included. During MIH, a score based on initial rhythm, QRS-upslope and systolic pressure resulted in an area under curve (AUC) of 0.82 and accuracy of 80% for survival. After rewarming, a score based on admission rhythm, sum of 12 lead QRS voltages, and mean lateral ST segment level in leads I and V6 resulted in an AUC of 0.88 and accuracy of 85% for survival. ECG can assist with early prognostication in unconscious survivors of OHCA during MIH and after rewarming.

The spatial QRS-T angle outperforms the Italian and Seattle ECG-based criteria for detection of hypertrophic cardiomyopathy in pediatric patients.

INTRODUCTION: The spatial peaks QRS-T angle has been shown to differentiate adult patients with hypertrophic cardiomyopathy (HCM) from controls. We hypothesized that the spatial peaks QRS-T angle would, in isolation, be more accurate than the Italian 12-lead ECG Pre-participation Screening criteria or the Seattle criteria for detecting hypertrophic cardiomyopathy (HCM) in pediatric patients. METHODS: A retrospective study of pediatric patients with HCM compared to age and gender-matched control patients was undertaken. Significance, odds ratios, sensitivity and specificity of HCM detection of the visually derived spatial peaks QRS-T angle were compared to those of traditional 12-lead ECG criteria using: 1) Italy's National Pre-participation Screening Programme criteria; and 2) described criteria from Seattle. RESULTS: ECG results from 130 pediatric HCM patients (14.2±4.4years) were compared to 470 control patients (normal echocardiograms, mean age 13.4±4.6years). Mean±standard deviation (SD) values for spatial peaks QRS-T angles were 120.4±40.7 and 21.3±13.7 degrees for HCM and controls, respectively (P<0.001). A spatial peaks QRS-T angle cutoff value of >54.9 degrees yielded greater sensitivity and specificity (93.1% and 98.7%, respectively) for detecting HCM over ECG criteria from Italy (68.5% and 48.1%, respectively) or Seattle (64.6% and 78.9%, respectively) with odds ratios at 1039.70 (95% CI 363.03 to 2977.67), 2.01 (95% CI 1.33 to 3.04) and 6.84 (4.49-10.44), respectively. CONCLUSION: In our cohort, a visually derived spatial peaks QRS-T angle has increased sensitivity and specificity for detection of HCM in pediatric patients compared to currently utilized Italian or Seattle ECG criteria.

Visual transform applications for estimating the spatial QRS-T angle from the conventional 12-lead ECG: Kors is still most Frank.

BACKGROUND: The 12-lead ECG-derived spatial QRS-T angle has prognostic and diagnostic utility, but most ECG machines currently fail to report it. The primary goal was to determine if reasonably accurate methods exist for rapid visual estimations of the spatial peaks QRS-T angle from conventional 12-lead ECG tracings. METHODS AND RESULTS: Simultaneous 12-lead and Frank XYZ-lead recordings were obtained from a publicly available database for 100 post-myocardial infarction patients and 50 controls. ANOVA, Pearson's correlation coefficients and concordance plots were used to evaluate agreement for spatial peaks QRS-T angle results from the true Frank leads versus from several visually applied 12-to-Frank XYZ-lead transforms. The latter included Kors et al.'s regression and quasi-orthogonal, Bjerle and Arvedson's quasi-orthogonal, Dower's inverse, and Hyttinen et al.'s, Dawson et al.'s and Guillem et al.'s transforms. Spatial peaks QRS-T angles derived from the true Frank leads were not statistically significantly different from those derived from any visually applied transform. Of the visually applied transforms, the Kors' regression and Kors' quasi-orthogonal yielded the highest Pearson correlation coefficients against the gold-standard true Frank lead results [0.84 and 0.77, respectively, when individuals with bundle branch blocks were included (N=150), and 0.88 and 0.80, respectively, when individuals with bundle branch blocks were excluded (N=137)]. Bland-Altman 95% confidence intervals showed similar results, with the two Kors'-related methods also having the narrowest confidence intervals. CONCLUSIONS: When visually applied, the Kors' regression-related and quasi-orthogonal transforms allow for reasonably precise spatial peaks QRS-T estimates and thus a potentially practical way to visually estimate spatial peaks QRS-T angles from conventional 12-lead ECGs.

Heart age gap estimated by explainable advanced electrocardiography is associated with cardiovascular risk factors and survival.

Aims: Deep neural network artificial intelligence (DNN-AI)-based Heart Age estimations have been presented and used to show that the difference between an electrocardiogram (ECG)-estimated Heart Age and chronological age is associated with prognosis. An accurate ECG Heart Age, without DNNs, has been developed using explainable advanced ECG (A-ECG) methods. We aimed to evaluate the prognostic value of the explainable A-ECG Heart Age and compare its performance to a DNN-AI Heart Age. Methods and results: Both A-ECG and DNN-AI Heart Age were applied to patients who had undergone clinical cardiovascular magnetic resonance imaging. The association between A-ECG or DNN-AI Heart Age Gap and cardiovascular risk factors was evaluated using logistic regression. The association between Heart Age Gaps and death or heart failure (HF) hospitalization was evaluated using Cox regression adjusted for clinical covariates/comorbidities. Among patients [n = 731, 103 (14.1%) deaths, 52 (7.1%) HF hospitalizations, median (interquartile range) follow-up 5.7 (4.7-6.7) years], A-ECG Heart Age Gap was associated with risk factors and outcomes [unadjusted hazard ratio (HR) (95% confidence interval) (5 year increments): 1.23 (1.13-1.34) and adjusted HR 1.11 (1.01-1.22)]. DNN-AI Heart Age Gap was associated with risk factors and outcomes after adjustments [HR (5 year increments): 1.11 (1.01-1.21)], but not in unadjusted analyses [HR 1.00 (0.93-1.08)], making it less easily applicable in clinical practice. Conclusion: A-ECG Heart Age Gap is associated with cardiovascular risk factors and HF hospitalization or death. Explainable A-ECG Heart Age Gap has the potential for improving clinical adoption and prognostic performance compared with existing DNN-AI-type methods.

Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart.

BACKGROUND: DNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946. RESULTS: We studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: the Bayesian A-ECG-based heart age score of Lindow et al. 2022 and the deep neural network (DNN) ECG-based heart age score of Ribeiro et al. 2020. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel. We derived the total effects, average causal mediation effects (ACMEs), average direct effects (ADEs), and the proportion mediated [PM] with their 95% confidence intervals [CIs]. 498 participants (all 60-64 years) were included, with the youngest ECG heart age being 27 and the oldest 90. When exploring the associations between cardiometabolic risk factors and Bayesian A-ECG cardiac age, AgeAccelPheno appears to be a partial mediator, as ACME was 0.23 years [0.01, 0.52] p = 0.028 (i.e., PM≈18%) for diabetes, 0.34 [0.03, 0.74] p = 0.024 (i.e., PM≈15%) for high cholesterol, and 0.34 [0.03, 0.74] p = 0.024 (PM≈15%) for any CV risk factor. Similarly, AgeAccelGrim mediates ≈30% of the relationship between diabetes or high cholesterol and the DNN ECG-based heart age. When exploring the link between cardiometabolic risk factors and the A-ECG-based LVSD and LVER scores, it appears that AgeAccelPheno or AgeAccelGrim mediate 10-40% of these associations. CONCLUSION: By the age of 60, participants with accelerated DNA methylation appear to have older, weaker, and more electrically impaired hearts. We show that the harmful effects of CV risk factors on cardiac age and health, appear to be partially mediated by DNAm AgeAccelPheno and AgeAccelGrim. This highlights the need to further investigate the potential cardioprotective effects of selective DNA methyltransferases modulators.

Heart age estimated using explainable advanced electrocardiography.

Electrocardiographic (ECG) Heart Age conveying cardiovascular risk has been estimated by both Bayesian and artificial intelligence approaches. We hypothesised that explainable measures from the 10-s 12-lead ECG could successfully predict Bayesian 5-min ECG Heart Age. Advanced analysis was performed on ECGs from healthy subjects and patients with cardiovascular risk or proven heart disease. Regression models were used to predict patients' Bayesian 5-min ECG Heart Ages from their standard, resting 10-s 12-lead ECGs. The difference between 5-min and 10-s ECG Heart Ages were analyzed, as were the differences between 10-s ECG Heart Age and the chronological age (the Heart Age Gap). In total, 2,771 subjects were included (n = 1682 healthy volunteers, n = 305 with cardiovascular risk factors, n = 784 with cardiovascular disease). Overall, 10-s Heart Age showed strong agreement with the 5-min Heart Age (R2 = 0.94, p < 0.001, mean ± SD bias 0.0 ± 5.1 years). The Heart Age Gap was 0.0 ± 5.7 years in healthy individuals, 7.4 ± 7.3 years in subjects with cardiovascular risk factors (p < 0.001), and 14.3 ± 9.2 years in patients with cardiovascular disease (p < 0.001). Heart Age can be accurately estimated from a 10-s 12-lead ECG in a transparent and explainable fashion based on known ECG measures, without deep neural network-type artificial intelligence techniques. The Heart Age Gap increases markedly with cardiovascular risk and disease.