scholarly journals Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A De Marvao ◽  
K McGurk ◽  
S Zheng ◽  
M Thanaj ◽  
W Bai ◽  
...  

Abstract Background Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. Purpose To determine the population prevalence of HCM-associated sarcomeric variants, characterise their phenotypic manifestations, estimate penetrance, and identify associations between sarcomeric variants and clinical outcomes, we performed an observational study of 218,813 adults in the UK Biobank (UKBB), of whom 200,584 have whole exome sequencing (WES). Methods We carried out an integrated analysis of WES and cardiac magnetic resonance (CMR) imaging in UK Biobank participants stratified by sarcomere-encoding variant status. Computer vision techniques were used to automatically segment the four chambers of the heart (Figure 1). Cardiac motion analysis was used to derive strain and strain rates. Regional analysis of left ventricular wall thickness was performed using three-dimensional modelling of these segmentations. Results Median age at recruitment was 58 (IQR 50–63 years), and participants were followed up for a median of 10.8 years (IQR 9.9–11.6 years) with a total of 19,507 primary clinical events reported. The prevalence of rare variants (allele frequency <0.ehab724.17314) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), and the prevalence of pathogenic or likely pathogenic variants (SARC-P/LP) was 0.24% (n=474, 1 in 423). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events (MACE) compared to controls (HR 1.68, 95% CI 1.37–2.06, p<0.001), mainly due to heart failure endpoints (Figure 2: cumulative hazard curves with zoomed plots for lifetime risk of A) death and MACE or B) heart failure, stratified by genotype; genotype negative (SARC-NEG), carriers of indeterminate sarcomeric variants (SARC-IND) or SARC-P/LP; C) Forest plot of comparative lifetime risk of clinical endpoints by genotype). While males had a higher overall risk of adverse outcomes, the incremental genetic risk from SARC-P/LP mutations was greater in females (HR for females: 2.18 CI 1.65–2.89, p<0.001; HR for males: 1.42 CI 1.05–1.9, p=0.02). In 21,322 participants with CMR, SARC-P/LP were associated with asymmetric increase in left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7–31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk. Conclusions In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM but are associated with increased risk of adverse cardiovascular outcomes and a sub-clinical cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was supported by the Medical Research Council, UK (MC-A651-53301); National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre; NIHR Royal Brompton Cardiovascular Biomedical Research Unit; British Heart Foundation (NH/17/1/32725, RG/19/6/34387, RE/18/4/34215).

2021 ◽  
Author(s):  
Antonio de Marvao ◽  
Kathryn A McGurk ◽  
Sean L Zheng ◽  
Marjola Thanaj ◽  
Wenjia Bai ◽  
...  

AbstractBackgroundHypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.MethodsWe compared outcomes and cardiovascular phenotypes in UK Biobank participants with whole exome sequencing stratified by sarcomere-encoding variant status.ResultsThe prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), of which 0.24% (n=474, 1 in 423) were pathogenic or likely pathogenic variants (SARC-P/LP). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events compared to controls (HR 1.68, 95% CI 1.37-2.06, p<0.001), mainly due to heart failure (HR 4.40, 95% CI 3.22-6.02, p<0.001) and arrhythmia (HR 1.55, 95% CI 1.18-2.03, p=0.002). In 21,322 participants with cardiac magnetic resonance imaging, SARC-P/LP were associated with increased left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) and concentric remodelling (mass/volume ratio: 0.63±0.12 vs 0.58±0.09 g/mL, p<0.001), but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7-31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk (HR 1.00 95% CI 0.92-1.08, p=0.9).ConclusionsIn the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM but are associated with an increased risk of adverse cardiovascular outcomes and a sub-clinical cardiomyopathic phenotype. In contrast, rare sarcomeric variants that do not meet criteria to be classified as P/LP appear to have minimal clinical impact.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ethan J Rowin ◽  
Barry J Maron ◽  
Tammy S Haas ◽  
John R Lesser ◽  
Mark S Link ◽  
...  

Background: Increasing penetration of high spatial resolution cardiovascular magnetic resonance (CMR) imaging into routine cardiovascular practice has resulted in more frequent identification of a subset of hypertrophic cardiomyopathy (HCM) patients with thin-walled, scarred left ventricular (LV) apical aneurysms. Prior experience involved relatively small numbers of patients with short follow-up and therefore the risk associated with this subgroup remains incompletely defined. Therefore, we assembled a large HCM cohort with LV apical aneurysms and long-term follow-up in order to clarify clinical course and prognosis. Methods and Results: Of 2,400 HCM patients, 60 (2.5%) were identified by CMR with LV apical aneurysm, 24 to 86 years of age, including 19 (32%) <45 years old; 70% male, and followed for 5.6 ± 3.5 years. Over the follow-up period, 24 patients experienced 31 adverse disease-related complications including: appropriate implantable cardioverter-defibrillator discharge for VT/VF (n=11), received or listed for heart transplant (n=6), heart failure death (n=5), nonfatal thromboembolic events (n=4), resuscitated out-of-hospital cardiac arrest (n=3), and sudden death (n=2). In addition, an intracavitary thrombus was identified in the apical aneurysm in 9 patients without a thromboembolic history. Combined HCM-related death and aborted life threatening event rate was 8.6% per year, nearly 6-fold greater than the 1.5% annual mortality rate reported in the general HCM population. Conclusions: Patients with LV apical aneurysms represent a high-risk subgroup within the diverse HCM spectrum, associated with substantial increased risk for disease-related morbidity and mortality, including advanced heart failure, thromboembolic stroke and sudden death. Identification of this unique HCM phenotype should prompt consideration for primary prevention ICD, and anticoagulation for stroke prophylaxis.


Author(s):  
Carmen Chan ◽  
Martin S Maron

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy and the most common cause of sudden death in young people, as well as a cause of limiting heart failure symptoms at any age. Mutations in the cardiac sarcomere, the structural apparatus of the heart muscle, cause HCM and a diagnosis is made when maximal left ventricular (LV) wall thickness is ≥15 mm in the absence of another cause. Cardiovascular magnetic resonance (CMR) can reliably identify areas of increased LV wall thickness, as well as detailed characterization of myocardial structures such as the papillary muscles and mitral valve, with implications on management strategies. In addition, contrast-enhanced CMR with late gadolinium enhancement sequences (LGE) can identify areas of myocardial fibrosis/scarring in patients with HCM. Extensive LGE is an important marker for development of future systolic dysfunction and may identify patients at increased risk for ventricular tachyarrhythmias and cardiac mortality. As a result, CMR currently serves an important and evolving role in the evaluation of HCM patients by providing information with regard to diagnosis, morphology, and clinical course in HCM patients.


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Rosca ◽  
D Ciuperca ◽  
L Mandes ◽  
M Trofin ◽  
A Calin ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Although earlier publications suggested a more benign clinical course for patients (pts) with apical hypertrophic cardiomyopathy (ApHCM), recent studies report increased morbidity and mortality, comparable to the prognosis of other HCM variants. Moreover, information regarding cardiac remodelling and its relationship with symptoms in pts with ApHCM is scarce. The aim of our study was to assess left ventricular (LV), right ventricular (RV) and left atrial (LA) remodelling in pts with ApHCM in comparison with non-apical variants of HCM (nonApHCM), and the impact of cardiac remodelling on heart failure symptoms. Methods One hundred fifty-one consecutive pts with HCM (52 ± 16 yrs, 47% men) in sinus rhythm and with preserved LV ejection fraction (16 pts with ApHCM and 135 pts with nonApHCM), were prospectively enrolled. Comprehensive echocardiography was performed in all, including the measurement of maximal LV wall thickness (LVWT), RV free wall thickness (RVWT) and maximal LA volume indexed to body surface area (LAVi). Global LV strain (ɛ), RVɛ, LAɛ and end-diastolic LA strain rate (ASr) were measured using speckle-tracking echocardiography (STE). The ratio of E to average e’ was used to estimate LV filling pressure. The degree of mitral regurgitation (1/2/3) has also been assessed. Heart failure symptoms were defined according to the New York Heart Association (NYHA) classification. Results Forty-eight pts in nonApHCM group had intraventricular obstruction. There were no significant differences between pts with and without ApHCM regarding: age (58 ± 20 vs 52 ± 16 yrs), gender distribution, RVWT, LVɛ (-14.9 ± 2.7 vs -13.9 ± 3.5 %), RVɛ (-19.6 ± 3.6 vs -10.0 ± 5.0%), LAɛ (19.2 ± 5.8 vs 16.4 ± 7.1%)(p &gt; 0.05 for all). Pts with ApHCM had lower values for LVWT (17.2 ± 1.9 vs 21.4 ± 5.2 mm, p = 0.002), E/e’ (12.0 ± 5.8 vs 17.6 ± 8.5, p = 0.02) and LAVi (48 ± 16 vs 61 ± 25, p = 0.03) compared to pts with nonApHCM. Pts with ApHCM had slightly better LA contractile function as assessed by ASr (-1.23 ± 0.50 vs -0.97 ± 0.49 sec-1, p = 0.05). Mitral regurgitation was more often severe in nonApHCM pts (56/42/31 vs 10/4/0, p &lt; 0.001). There was no significant difference between the percentage of symptomatic pts (NYHA class ≥2) in ApHCM vs nonApHCM group (p = 0.3). In the ApHCM group, symptomatic pts had significantly lower ASr compared to asymptomatic pts (-0.98 ± 0.35 vs -1.61 ± 0.46 sec-1, p = 0.01). Conclusions Despite of lower LVWT values, less severe MR and no obstruction, pts with apical HCM have similar prevalence of heart failure symptoms, and similar LV, RV and LA dysfunction compared to pts with non-apical HCM. Symptomatic pts with apical HCM have worse LA contractile function compared to asymptomatic pts.


Author(s):  
Vasilisa S. Ermolenko ◽  
I. V. Silnova ◽  
E. N. Basargina

N-terminal pro-brain natriuretic peptide (NT-proBNP) is the unbiased marker of congestive heart failure. Levels of this marker have not been studied in children with hypertrophic cardiomyopathy (HCM). There are presented data of the comparison of blood concentrations of NT-proBNP in hereditary HCM and other diseases associated with myocardial hypertrophy in children. There was examined 41 patient (age: from 3 to 90 months) with myocardial hypertrophy The patients were divided into 3 groups. There was evaluated the interrelationship between NT-proBNP concentrations and the severity of heart failure and echocardiographic parameters. Results. It was established that in the first group of patients with hereditary HCM (41,4%) there was revealed the significant positive relationship between NT-proBNP concentrations and values of the bloodflow velocity and pressure gradient in the LV outflow track, interventricular septum thickness and LVposterior wall thickness (LVPWT), in cases from the second group (34.1%) with syndromes of malformations and metabolic diseases - with RV anterior wall thickness and LVposterior wall thickness, bloodflow velocity and pressure gradient in the RV outflow track, in the third group with myocardial remodeling against background of arterial hypertension the positive correlation was revealed with LVPWT, whereas negative one - with the fraction of left ventricular output. Maximal blood level of NT-proBNP in blood was detected in pronounced hemodynamic disturbances in patients from the second and third group Conclusion. NT-proBNP level assessment is necessary for differentiated diagnostics of HCM and associated diseases.


2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.


scholarly journals POSTERS (2)96CONTINUOUS VERSUS INTERMITTENT MONITORING FOR DETECTION OF SUBCLINICAL ATRIAL FIBRILLATION IN HIGH-RISK PATIENTS97HIGH DAY-TO-DAY INTRA-INDIVIDUAL REPRODUCIBILITY OF THE HEART RATE RESPONSE TO EXERCISE IN THE UK BIOBANK DATA98USE OF NOVEL GLOBAL ULTRASOUND IMAGING AND CONTINUEOUS DIPOLE DENSITY MAPPING TO GUIDE ABLATION IN MACRO-REENTRANT TACHYCARDIAS99ANTICOAGULATION AND THE RISK OF COMPLICATIONS IN PATIENTS UNDERGOING VT AND PVC ABLATION100NON-SUSTAINED VENTRICULAR TACHYCARDIA FREQUENTLY PRECEDES CARDIAC ARREST IN PATIENTS WITH BRUGADA SYNDROME101USING HIGH PRECISION HAEMODYNAMIC MEASUREMENTS TO ASSESS DIFFERENCES IN AV OPTIMUM BETWEEN DIFFERENT LEFT VENTRICULAR LEAD POSITIONS IN BIVENTRICULAR PACING102CAN WE PREDICT MEDIUM TERM MORTALITY FROM TRANSVENOUS LEAD EXTRACTION PRE-OPERATIVELY?103PREVENTION OF UNECESSARY ADMISSIONS IN ATRIAL FIBRILLATION104EPICARDIAL CATHETER ABLATION FOR VENTRICULAR TACHYCARDIA ON UNINTERRUPTED WARFARIN: A SAFE APPROACH?105HOW WELL DOES THE NATIONAL INSTITUTE OF CLINICAL EXCELLENCE (NICE) GUIDENCE ON TRANSIENT LOSS OF CONSCIOUSNESS (T-LoC) WORK IN A REAL WORLD? AN AUDIT OF THE SECOND STAGE SPECIALIST CARDIOVASCULAT ASSESSMENT AND DIAGNOSIS106DETECTION OF ATRIAL FIBRILLATION IN COMMUNITY LOCATIONS USING NOVEL TECHNOLOGY'S AS A METHOD OF STROKE PREVENTION IN THE OVER 65'S ASYMPTOMATIC POPULATION - SHOULD IT BECOME STANDARD PRACTISE?107HIGH-DOSE ISOPRENALINE INFUSION AS A METHOD OF INDUCTION OF ATRIAL FIBRILLATION: A MULTI-CENTRE, PLACEBO CONTROLLED CLINICAL TRIAL IN PATIENTS WITH VARYING ARRHYTHMIC RISK108PACEMAKER COMPLICATIONS IN A DISTRICT GENERAL HOSPITAL109CARDIAC RESYNCHRONISATION THERAPY: A TRADE-OFF BETWEEN LEFT VENTRICULAR VOLTAGE OUTPUT AND EJECTION FRACTION?110RAPID DETERIORATION IN LEFT VENTRICULAR FUNCTION AND ACUTE HEART FAILURE AFTER DUAL CHAMBER PACEMAKER INSERTION WITH RESOLUTION FOLLOWING BIVENTRICULAR PACING111LOCALLY PERSONALISED ATRIAL ELECTROPHYSIOLOGY MODELS FROM PENTARAY CATHETER MEASUREMENTS112EVALUATION OF SUBCUTANEOUS ICD VERSUS TRANSVENOUS ICD- A PROPENSITY MATCHED COST-EFFICACY ANALYSIS OF COMPLICATIONS & OUTCOMES113LOCALISING DRIVERS USING ORGANISATIONAL INDEX IN CONTACT MAPPING OF HUMAN PERSISTENT ATRIAL FIBRILLATION114RISK FACTORS FOR SUDDEN CARDIAC DEATH IN PAEDIATRIC HYPERTROPHIC CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS115EFFECT OF CATHETER STABILITY AND CONTACT FORCE ON VISITAG DENSITY DURING PULMONARY VEIN ISOLATION116HEPATIC CAPSULE ENHANCEMENT IS COMMONLY SEEN DURING MR-GUIDED ABLATION OF ATRIAL FLUTTER: A MECHANISTIC INSIGHT INTO PROCEDURAL PAIN117DOES HIGHER CONTACT FORCE IMPAIR LESION FORMATION AT THE CAVOTRICUSPID ISTHMUS? INSIGHTS FROM MR-GUIDED ABLATION OF ATRIAL FLUTTER118CLINICAL CHARACTERISATION OF A MALIGNANT SCN5A MUTATION IN CHILDHOOD119RADIOFREQUENCY ASSOCIATED VENTRICULAR FIBRILLATION120CONTRACTILE RESERVE EXPRESSED AS SYSTOLIC VELOCITY DOES NOT PREDICT RESPONSE TO CRT121DAY-CASE DEVICES - A RETROSPECTIVE STUDY USING PATIENT CODING DATA122PATIENTS UNDERGOING SVT ABLATION HAVE A HIGH INCIDENCE OF SECONDARY ARRHYTHMIA ON FOLLOW UP: IMPLICATIONS FOR PRE-PROCEDURE COUNSELLING123PROGNOSTIC ROLE OF HAEMOGLOBINN AND RED BLOOD CELL DITRIBUTION WIDTH IN PATIENTS WITH HEART FAILURE UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY124REMOTE MONITORING AND FOLLOW UP DEVICES125A 20-YEAR, SINGLE-CENTRE EXPERIENCE OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS (ICD) IN CHILDREN: TIME TO CONSIDER THE SUBCUTANEOUS ICD?126EXPERIENCE OF MAGNETIC REASONANCE IMAGING (MEI) IN PATIENTS WITH MRI CONDITIONAL DEVICES127THE SINUS BRADYCARDIA SEEN IN ATHLETES IS NOT CAUSED BY ENHANCED VAGAL TONE BUT INSTEAD REFLECTS INTRINSIC CHANGES IN THE SINUS NODE REVEALED BY I (F) BLOCKADE128SUCCESSFUL DAY-CASE PACEMAKER IMPLANTATION - AN EIGHT YEAR SINGLE-CENTRE EXPERIENCE129LEFT VENTRICULAR INDEX MASS ASSOCIATED WITH ESC HYPERTROPHIC CARDIOMYOPATHY RISK SCORE IN PATIENTS WITH ICDs: A TERTIARY CENTRE HCM REGISTRY130A DGH EXPERIENCE OF DAY-CASE CARDIAC PACEMAKER IMPLANTATION131IS PRE-PROCEDURAL FASTING A NECESSITY FOR SAFE PACEMAKER IMPLANTATION?

EP Europace ◽  
2016 ◽  
Vol 18 (suppl 2) ◽  
pp. ii36-ii47
Author(s):  
T. Philippsen ◽  
M. Orini ◽  
C.A. Martin ◽  
E. Volkova ◽  
J.O.M. Ormerod ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helen Sjöland ◽  
Jonas Silverdal ◽  
Entela Bollano ◽  
Aldina Pivodic ◽  
Ulf Dahlström ◽  
...  

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). Conclusions From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.


Author(s):  
Erika N Aagaard ◽  
Brede Kvisvik ◽  
Mohammad O Pervez ◽  
Magnus N Lyngbakken ◽  
Trygve Berge ◽  
...  

Abstract Aims Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease. Methods and results The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e’ (B = −2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all). Conclusion In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion.


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