Maximal Left Ventricular Wall Thickness Research Articles

Effectiveness of contemporary risk stratification in patients with hypertrophic cardiomyopathy: a pilot study

Abstract Introduction Risk stratification and primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a challenging discipline. When using current stratification systems, there is always a compromise between sensitivity and specificity. Objective In our pilot study, we sought to determine the incidence of SCD and the effectiveness of stratification systems, i.e., the ESC HCM Risk-SCD score and the system of individual major risk factors (RF) according to ACC/AHA in patients followed in an expert center. Methods Patients with HCM were risk-stratified and followed for 10 ± 8 years at the referral HCM center. Results Five hundred and five patients were stratified, and 71 (14%) were implanted with a cardioverter-defibrillator (ICD) based on risk stratification. ICD patients were stratified at age 39 ± 17 years, of which 26 (35%) were women, maximal left ventricular wall thickness (MLWT) was 23 ± 7 mm, and left atrial dimension (LA) 46 ± 7 mm. During follow-up, 12 (17%) patients had ≥ 1 appropriate ICD therapy at age 46 ± 19 years. Patients with ≥ 1 appropriate ICD therapy had an average 5-year ESC score of 1.8 ± 0.4% and an average ACC/AHA major RF of 1.4 ± 0.8, MLWT 25 ± 6 mm, LA 47 ± 7 mm. None of the ICD patients died of SCD. Five (7%) patients suffered from ICD complications, including 4 (6%) inappropriate shock, and one patient experienced infective endocarditis requiring system extraction. During follow-up, 118 (23%) patients died, of which 28 (6%) from HCM-related causes, 12 (2%) from stroke, 11 (2%) from advanced heart failure, one perioperatively (myectomy) and 4 (1%) patients died suddenly (SCD). The mean age of SCD patients at the time of stratification was 59 ± 14 years; all were male, MLWT 18 ± 5 mm, LA 49 ± 2 mm, mean ESC score 2.0 ± 0.9%, and three (75%) had no RF present according to ACC/AHA. The ESC HCM Risk-SCD score was markedly less sensitive (sensitivity 56%; 95% CI 21-86) but more specific (specificity 98%; 95% CI 96-99) than the ACC/AHA approach (sensitivity 77%; 95% CI 46-95; and specificity 71%; 95% CI 67-75) (Figure). Conclusion With current risk stratification, albeit imperfect, SCD is rare in HCM patients managed at an expert center.

Hemodynamic effects of right and biventricular pacing during exercise in hypertrophic obstructive cardiomyopathy

Abstract Background One third of patients with hypertrophic cardiomyopathy present with dynamic left ventricular outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medications, invasive septal reduction, or pacing. The importance of pacing site is unclear, and effects of pacing during physical activity have not been investigated. Purpose To determine the effect of right ventricular (RV) and biventricular (BiV) pacing, respectively, on LVOTO and cardiac output (CO) during exercise in patients with HOCM. Methods Patients with symptomatic HOCM, sinus rhythm, and no bundle branch block, scheduled for alcohol septal ablation (ASA), were eligible for inclusion. The day before ASA, we placed temporary pacing leads in the right atrium, the RV apex, and on the left ventricle’s lateral wall via the coronary sinus. LVOTO was assessed by echocardiography, and CO was measured by thermodilution with a pulmonary artery catheter. Patients performed supine cycling for 2 minutes until heart rate (HR) increased ≥20 bpm. We measured LVOTO and CO in sinus rhythm, and during cycling with atrial sensed RV pacing, and atrial sensed BiV pacing. The order of pacing sites was randomized, and the personnel performing echocardiography and CO measurements were blinded to the order of pacing. Results We included six patients (54±15 years) with a mean maximal left ventricular wall thickness of 16.7±1.8 mm. Resting LVOTO was 55.7±30.9 mmHg. The figures show LVOTO and CO in sinus rhythm (HR 85±10 bpm), RV pacing (HR 90±10 bpm), and BiV pacing (HR 91±9 bpm) during supine cycling. The LVOTO declined from 56±34 mmHg in sinus rhythm to 27±12 mmHg and 25±5 mmHg respectively for atrial sensed RV and BiV pacing. CO remained unchanged during sinus rhythm (9.0±1.2 L/min), atrial sensed RV pacing (9.0±1.7 L/min), and BiV pacing (8.9±1.5 L/min). Conclusion In this ongoing study evaluating cardiac pacing in HOCM, preliminary data indicate that both RV and BiV pacing are effective in reducing LVOTO during exercise, without compromising CO.

Phenotype progression in pediatric RASopathy-associated hypertrophic cardiomyopathy

Abstract Background RASopathy syndromes represent the second most common cause of hypertrophic cardiomyopathy (HCM) in children. RASopathy associated HCM (Ras-HCM) has been shown to differ both in cardiac phenotype and long-term outcomes from sarcomeric HCM. However, there is a lack of knowledge from large cohort studies of how the cardiac phenotype of Ras-HCM changes over time. Aim To describe cardiac phenotype changes over time in children with Ras-HCM Methods Retrospective data from 148 patients diagnosed with Ras-HCM aged <18 years with ³2 follow-up visits were included. Clinical and echocardiographic data were collected at baseline assessment, 1, 2, and 5 years of follow up. Separate analyses were performed for patients who survived, versus patients who died or had a heart transplant (censoring events). Results One-hundred-and-two (68.9%) patients with Noonan syndrome, 25 (16.9%) with Noonan-syndrome with multiple lentigines, 10 (6.8%) with Costello syndrome, 9 (6.1%) with cardio-facio-cutaneous syndrome and 2 (1.4%) patients with Noonan-like syndrome with a median age of diagnosis 0.16 years (0.01-0.89) were seen at a median baseline age of 1.41 years (0.37-5.71) and followed up for a median of 12.1 years (4.8-17.4). During follow up, 18 patients (12.2%) died at a median age of 1.8 years (0.5-8.7) and 17 (12.5%) had a left ventricular myectomy, at a median age of 7.0 years (3.1-12.7). At baseline evaluation, patients who died compared to those who survived had a lower median age [0.4 years (0.1-0.8) versus 2.3 years (0.5-7.6), p<0.001], a higher proportion of them had a NYHA class>I (54.5% vs 15.1%, p<0.001), a higher maximal left ventricular wall thickness (MLVWT) z-score [13.4 (7.5) vs 9.6 (6.2), p=0.04], a higher proportion of left ventricular outflow tract obstruction (LVOTO) [64.7% vs 43.8%, p=0.087] and a higher proportion of biventricular hypertrophy [75% vs 49.2%, p=0.045]. For survivors, the MLVWT z-score improved over follow up [+9.6(6.2) at baseline vs. +7.9(5.5) at 5 years, p=0.072], and the proportion of patients with LVOTO (43.8% at baseline vs. 27.9% at 5 years, p=0.019) and biventricular hypertrophy (49.2% at baseline vs. 35.5% at 5 years, p=0.012) decreased over follow up. Conclusion While at baseline evaluation Ras-HCM has a high burden of symptoms, biventricular hypertrophy and LVOTO for patients who die or have a heart transplant, we have demonstrated that for survivors, over follow up, the phenotype becomes milder.Table 1

Automated deep learning approach for identifying etiologies of hypertrophic phenocopies by echocardiography

Abstract Background Left ventricular hypertrophy (LVH) is an indicator of poor prognosis across various cardiovascular diseases and is developed by various etiologies. Transthoracic echocardiography (TTE) is the most available cardiac imaging tool to detect LVH. However, it is still challenging to differentiate three non-ischemic cardiomyopathies which frequently presenting LVH: Fabry cardiomyopathy (FC), hypertrophic cardiomyopathy (HCM), and cardiac amyloidosis (CA) from morphology or cardiac function evaluated by TTE. Purpose We aimed to develop stepwise deep learning models to differentiate FC, HCM, and CA using radiomics extracted from TTE. Methods We conducted a retrospective cohort study between 2011 and 2022 in Taiwan. Patients with left ventricular (LV) mass index≥95g/m² in women or ≥115g/m² in men, or the maximal LV wall thickness≥13mm on echocardiography were enrolled. The TTE automatic processing models included four steps: image quality assessment, view classification, auto-segmentation of interventricular septum (IVS), and dynamic radiomics analysis. One echocardiographic study was scanned per patient, and each study contains multiple cardiac cycles. One sample was extracted from each cycle and all samples were evaluated by image quality assessment and view classification model that based on VGG16. Samples with apical four (A4C) and apical five chamber (A5C) views were retained for following steps. Manual contouring of the septal region served as the ground truth for auto-segmentation based on U-Net. The last step was the extraction of dynamic radiomic features from IVS and the dynamic radiomic features were analyzed using an LSTM model to differentiate three hypertrophic cardiomyopathies. Results There were 103 patients with FC, 96 patients with HCM, and 49 patients with CA in this study. Patients with CA were older and had lower LV ejection fraction (EF) than those with FC or HCM (age: 65.8±9.7 vs. 59.3±11.1 vs. 58.6±14.2 years, P=0.002; LVEF: 56.6±10.8 vs. 61.9±8.8 vs. 64.5±8.3%, P<0.001). In addition, patient with FC had larger LV mass index than those with HCM or CA. (Fig. 2A) The details of the performances of four stepwise models were provided in Figure 2 (B-F). The image quality assessment and view classification models achieved accuracies of 91.7% and 95.2%, respectively. The auto-segmentation had the median Dice score as 0.88 for contouring IVS. The results indicated that deep learning algorithms had great ability to recognize different views with proper image quality, and could contour the IVS adequately. The accuracy of dynamic radiomics-based LSTM model to differentiate three hypertrophic phenocopies was 74.5%. Conclusion We developed an automatic process with four stepwise models for analyzing the radiomics of IVS on TTE to differentiate FC, HCM and CA with the modest performance by LSTM model. The developed automatic models may provide potential implications to identify various etiologies LVH in the future.Figure 1-Workflow of this studyFigure 2-Performances of stepwise models

Imaging predictors of adverse prognosis in fabry disease cardiomyopathy: a systematic review and meta-analysis

Abstract Background Cardiac involvement represents the main cause of death in patients with Fabry disease (FD). Echocardiography and Cardiac Magnetic Resonance (CMR) have an established diagnostic role, but their prognostic value remains unresolved. This systematic review and meta-analysis sought to assess the prognostic implications of imaging parameters in FD. Methods PubMed, ClinicalTrials.gov, Embase and Cochrane Library databases were searched for studies published from inception through to October 1, 2023. Full-length original papers including FD patients undergoing baseline imaging assessment and clinical follow-up were selected. Pre-defined study outcomes were a cardiovascular endpoint and a composite clinical endpoint. A meta-analysis of the studies investigating the effect of single imaging parameters on a pre-specified cardiovascular endpoint and a separate analysis on a pre-specified composite clinical endpoint were performed to obtain the pooled estimates for the association between the imaging parameters and the study outcome. The study protocol was registered in PROSPERO. Results Thirteen studies including 1,399 FD patients (44.8% males) were selected. At pooled analysis, late gadolinium enhancement (HR 4.39; 95% CI 2.5-7.71), left atrium volume indexed (HR 1.02 per ml/m2; 95% CI 1.01-1.04), E/e’ (HR 1.14 per unit increase; 95% CI 1.08-1.21), left ventricular (LV) mass indexed (HR 1.014 per mg/m2; 95% CI 1.006-1.023), maximum LV wall thickness (HR 1.19 per mm, 95% CI 1.04-1.36), LV-global longitudinal strain (HR 1.2 per unit increase; 95% CI 1.2-1.27), were significantly associated with the cardiovascular endpoint, whereas T1-mapping (p=0.115) and LV-ejection fraction (p=0.305) were not. T1-mapping was associated with the composite endpoint (HR 0.986 per msec increase; 95% CI 0.976-0.997). Meta-regression analysis did not show any significant interaction between each of the potential effect modifiers. Conclusion This meta-analysis demonstrates a robust prognostic value regarding several imaging parameters in FD, specifically indexes of LV mass and wall thickness, diastolic dysfunction, LV-GLS, and LGE presence. These findings support multimodality cardiovascular imaging, including CMR, in FD disease patients to predict long-term prognosis and call for longitudinal multicentre studies to develop multi-modality-imaging derived risk-score algorithms.

Association between impaired left ventricular global longitudinal strain and B-type natriuretic peptide in obstructive hypertrophic cardiomyopathy

Abstract Background Left ventricular global longitudinal strain (LV-GLS) is considered valuable in explaining impaired left ventricular contractility in hypertrophic cardiomyopathy (HCM) with preserved ejection fraction and is associated with worse outcome. Elevated B-type natriuretic peptide (BNP) is a biomarker of increased LV wall stretch and a risk factor of heart failure, mortality, and other adverse cardiovascular events. However, relationship between GLS and BNP has not received sufficient attention in the obstructive variant of HCM. Purpose This study aimed to determine the association between echocardiographic LV-GLS and plasma BNP in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods A total of 145 consecutive patients (32% females) with symptomatic HOCM were enrolled in the retrospective study. HOCM was defined with a maximum end-diastolic wall thickness ≥15mm without other etiologies for LV hypertrophy, and peak LV outflow tract (LVOT) gradient ≥30mmHg. The echocardiographic parameters regarding LV geometry, loading conditions, and GLS were evaluated according to guidelines. Patients were divided into two groups according to absolute GLS values (greater or lower than median LV-GLS). Patient baseline clinical data, echocardiographic parameters, and BNP were compared. Univariate and multivariable regression analysis were applied to identify the independent determinator of LV-GLS. Results The median value of LV-GLS of this study cohort was -13.4%. Eighty-one patients (47.6±13.4 years-old) had a |GLS|≥13.4% and 64 individuals (48.7±12.6 years-old) had a |GLS|<13.4%. No differences were found in age, gender, physical examinations, LVEF, cardiovascular comorbidities, or active medications between the two groups, except for body mass index (BMI). Patients with |GLS|≥13.4% had statistically lower BMI (24.58±2.42 vs. 26.00±3.12kg/m², p=0.030). BNP was found significantly elevated in patients with |GLS|<13.4% when compared with individuals with |GLS|≥13.4% {median (IQR); 550.05 (214.50, 899.35) vs. 182.40 (78.90, 479.90)pg/mL, p=0.004}. In univariate regression analysis, decreased |GLS| was associated with male gender, maximum and mean LV wall thickness, peak LVOT gradient, reduced mitral annular e’ velocity, elevated BNP and cardiac troponin I. In multivariable regression analysis, GLS was found independently associated with mean LV wall thickness and BNP. Conclusions In patients with symptomatic HOCM with preserved ejection fraction, impaired LV-GLS was found to be associated with plasma BNP and mean LV wall thickness, independent of gender, age, loading conditions, LVEF, or LVOT gradient. Reduced GLS may be a more sensitive surrogate in assessing increased myocardial wall tension or stretch, rather than LV contractility in these patients. Therefore, the interpretation of GLS in HOCM should shift away from systolic interest toward emphasizing its potential value in risk stratification of diastolic heart failure with preserved LVEF.Figure 1

Deep learning of echocardiography distinguishes between presence and absence of late gadolinium enhancement on cardiac magnetic resonance in patients with hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) can cause myocardial fibrosis, which can be a substrate for fatal ventricular arrhythmias and subsequent sudden cardiac death. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) represents myocardial fibrosis and is associated with sudden cardiac death in patients with HCM, CMR is resource-intensive, can carry an economic burden, and is sometimes contraindicated. In this study for patients with HCM, we aimed to distinguish between patients with positive and negative LGE on CMR using deep learning of echocardiographic images.MethodsIn the cross-sectional study of patients with HCM, we enrolled patients who underwent both echocardiography and CMR. The outcome was positive LGE on CMR. Among the 323 samples, we randomly selected 273 samples (training set) and employed deep convolutional neural network (DCNN) of echocardiographic 5-chamber view to discriminate positive LGE on CMR. We also developed a reference model using clinical parameters with significant differences between patients with positive and negative LGE. In the remaining 50 samples (test set), we compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the DCNN-derived probability and the reference model.ResultsAmong the 323 CMR studies, positive LGE was detected in 160 (50%). The reference model was constructed using the following 7 clinical parameters: family history of HCM, maximum left ventricular (LV) wall thickness, LV end-diastolic diameter, LV end-systolic volume, LV ejection fraction < 50%, left atrial diameter, and LV outflow tract pressure gradient at rest. The discriminant model combining the reference model with DCNN-derived probability significantly outperformed the reference model in the test set (AUC 0.86 [95% confidence interval 0.76–0.96] vs. 0.72 [0.57–0.86], P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the combined model were 0.84, 0.76, 0.78, and 0.83, respectively.ConclusionCompared to the reference model solely based on clinical parameters, our new model integrating the reference model and deep learning-based analysis of echocardiographic images demonstrated superiority in distinguishing LGE on CMR in patients with HCM. The novel deep learning-based method can be used as an assistive technology to facilitate the decision-making process of performing CMR with gadolinium enhancement.

Transthyretin amyloidosis prevalence and characteristics in Korean patients with heart failure with preserved or mildly reduced ejection fractions

The diagnosis and awareness of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in heart failure with left ventricular ejection fraction (LVEF) > 40% remains under-recognized. This study aimed to investigate the prevalence and characteristics of ATTR-CM in patients with heart failure with LVEF > 40%. Patients with LVEF > 40% and maximal left ventricular wall thickness (MWT) > 10 mm who underwent bone scintigraphy were retrospectively investigated. Patients with a definite cause of heart failure were excluded. ATTR-CM was diagnosed when grade 2 or 3 myocardial uptake was observed on scintigraphy. Among 97 patients (male, 62.5%; median age, 69 years), 13 (13.4%) were diagnosed with ATTR-CM (wild type, 69.2%; hereditary type, 30.8%). Age or biomarker levels did not differ significantly; however, all patients with ATTR-CM were male. The ATTR-CM group had a significantly higher prevalence of polyneuropathy or carpal tunnel syndrome than the non-ATTR-CM group, accompanied by a longer PR interval, thicker MWT, larger left atrial volume index, and higher E/e′. Accordingly, ATTR was present in a substantial number, particularly among men. Clinicians should suspect ATTR when a male patient exhibits neurologic symptoms, diastolic dysfunction, and a long PR interval.

Prevalence of cardiomyopathy and cardiac mortality in a colony of non-purebred cats in New Zealand

ABSTRACT Aims To evaluate the prevalence of subclinical cardiomyopathy and cardiac mortality in a research colony of non-purebred cats, established as a model of the wider cat population in New Zealand. Methods All apparently healthy, compliant, non-pregnant, non-neonatal cats in the colony at the Centre for Feline Nutrition (Massey University, Palmerston North, NZ) underwent physical examination and echocardiography using a 4.4–6.2-MHz probe by a board-certified veterinary cardiologist. Cardiac phenotype was classified following current guidelines. Hypertrophic cardiomyopathy (HCM) phenotype was defined as an end-diastolic left ventricular wall thickness ≥ 6 mm. Colony mortality data from February 2012 to February 2022 was reviewed to determine cardiac mortality. Results Cats (n = 132; 65 females and 67 males) included in the study had a median age of 4.1 (IQR 3.0–8.0) years. Thirty-two (24%) cats had a heart murmur, and three (2%) cats had an arrhythmia. Echocardiography revealed heart disease in 24 (18.2%) cats, including 23 with an HCM phenotype and one with a restrictive cardiomyopathy phenotype. Of the cats with the HCM phenotype, 3/23 had systemic hypertension or hyperthyroidism or both, and these cats were excluded from the final diagnosis of HCM (20/132; 15.2 (95% CI = 9.5–22.4)%). Between 2012 and 2022, 168 colony cats died, with 132 undergoing post-mortem examination. Heart disease was considered the cause of death in 7/132 (5.3%; 95% CI = 2.2–10.6%) cats; five had HCM, one a congenital heart defect, and one myocarditis. The overall prevalence of death related to HCM in the colony during this period was 3.8% (95% CI = 1.2–8.6%). Three cats with HCM and the cat with a congenital heart defect died unexpectedly without prior clinical signs, while congestive heart failure was observed prior to death in two cats with HCM and the cat with myocarditis. Additionally, 30/132 (22.7%) cats had cardiac abnormalities but died for non-cardiac reasons. Conclusions Subclinical cardiomyopathy, specifically HCM, was common in cats in the colony. Given that the colony originated as a convenience selection of non-purebred cats in New Zealand, the true prevalence of HCM in the wider New Zealand population is likely to fall within the 95% CI (9.5–22%). The proportion of deaths of colony cats due to HCM was lower (3.8%) supporting the conclusion that subclinical cardiomyopathy may not progress to clinical disease causing death. Clinical relevance Veterinarians should be aware of the high prevalence of subclinical HCM when treating cats. Abbreviations CAM: Systolic anterior motion of the chordae tendineae; CFN: Centre for Feline Nutrition; HCM: Hypertrophic cardiomyopathy; LA/Ao: Left atrial to aortic ratio; LV FS: Left ventricular fractional shortening; LVIDd: Left ventricular internal diameters in end-diastole; LVIDs: Left ventricular internal diameter in end-systole; LVWT: Max Maximum left ventricular wall thickness; SAM: Systolic anterior motion of the mitral valve; 2D: Two-dimensional

Prevalence and characteristics of transthyretin amyloid cardiomyopathy in hypertrophic cardiomyopathy.

Recognition of transthyretin amyloid cardiomyopathy is increasing due to advances in cardiac imaging and diagnostic strategies, but questions remain regarding disease frequency and characteristics. We examined the prevalence and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy of unascertained aetiology. TTRACK was a multicentre, non-interventional, cross-sectional epidemiologic study funded by Pfizer and conducted in 20 hospitals and medical centres in 11 countries (NCT03842163). Eligible patients were aged ≥50years, had hypertrophic cardiomyopathy (maximal end-diastolic left ventricular wall thickness ≥15mm on echocardiogram) without an identified genetic or alternative origin at study enrolment, and underwent 99mTechnetium bone scintigraphy, with or without single photon emission computed tomography (SPECT). Cardiac-versus-bone uptake on scans was visually scored from 0 to 3 (Perugini scoring). Patients with grades 1-3 underwent monoclonal protein and laboratory testing and transthyretin (TTR) gene sequencing. Of 766 eligible patients, 691 (90.2%) had scintigraphy alone and 75 (9.8%) scintigraphy plus SPECT. Two hundred and eight patients (27.2%) had grade 2 or 3 cardiac uptake on scintigraphy; 144 (18.8%) had grade 2 or 3 cardiac uptake and no evidence of plasma cell dyscrasia and were diagnosed with transthyretin amyloid cardiomyopathy. Of patients with transthyretin amyloid cardiomyopathy, 11 (7.6%) had a pathogenic TTR gene variant and 34 (23.8%), 74 (51.7%), and 35 (24.5%) had New York Heart Association class I, II, and III/IV heart failure (HF) symptoms, respectively. Clinical and laboratory diagnostic characteristics were observed in ≥90% of patients with transthyretin amyloid cardiomyopathy. The characteristics most strongly associated with transthyretin amyloid cardiomyopathy on multivariable analysis were carpal tunnel syndrome (odds ratio [OR] 54.3; P<0.0001) and male sex (OR 7.9; P<0.0001). In the TTRACK study, almost one in five patients ≥50years of age with hypertrophic cardiomyopathy had transthyretin amyloid cardiomyopathy. Greater awareness of the frequency and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy are needed to help improve early detection of this debilitating but treatable disease.

Device-measured physical activity and cardiac structure by magnetic resonance.

Although extreme cardiac adaptions mirroring phenotypes of cardiomyopathy have been observed in endurance athletes, adaptions to high levels of physical activity within the wider population are under-explored. Therefore, in this study, associations between device-measured physical activity and clinically relevant cardiac magnetic resonance volumetric indices were investigated. Individuals without known cardiovascular disease or hypertension were included from the UK Biobank. Cardiac magnetic resonance data were collected between 2015 and 2019, and measures of end-diastolic chamber volume, left ventricular (LV) wall thickness, and LV ejection fraction were extracted. Moderate-to-vigorous-intensity physical activity (MVPA), vigorous-intensity physical activity (VPA), and total physical activity were assessed via wrist-worn accelerometers. A total of 5977 women (median age and MVPA: 62 years and 46.8 min/day, respectively) and 4134 men (64 years and 49.8 min/day, respectively) were included. Each additional 10 min/day of MVPA was associated with a 0.70 [95% confidence interval (CI): 0.62, 0.79] mL/m2 higher indexed LV end-diastolic volume (LVEDVi) in women and a 1.08 (95% CI: 0.95, 1.20) mL/m2 higher LVEDVi in men. However, even within the top decile of MVPA, LVEDVi values remained within the normal ranges [79.1 (95% CI: 78.3, 80.0) mL/m2 in women and 91.4 (95% CI: 90.1, 92.7) mL/m2 in men]. Associations with MVPA were also observed for the right ventricle and the left/right atria, with an inverse association observed for LV ejection fraction. Associations of MVPA with maximum or average LV wall thickness were not clinically meaningful. Results for total physical activity and VPA mirrored those for MVPA. High levels of device-measured physical activity were associated with cardiac remodelling within normal ranges.

Influencing and prognostic factors of end-stage hypertrophic cardiomyopathy.

End-stage hypertrophic cardiomyopathy (ES-HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES-HCM. A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF)<50% were defined as having ES-HCM, and a control group (LVEF≥50%) was generated from the collected medical records of HCM. The patients were matched in a ratio of 4:1 based on age and sex. Logistic regression analysis was used to determine the influencing factors of ES-HCM. Kaplan-Meier survival analysis was performed to analyse the clinical outcomes of ES-HCM patients. A total of 250 inpatients with HCM were enrolled in the study; 50 patients had ES-HCM, and 200 had HCM with LVEF≥50%. The mean age of the patients at enrolment was 62.5±10.3years, and 215 patients (215/250, 86.0%) were male. The median follow-up time of the patients was 2.8 (1.4-5.4) years. The incidence of all-cause death and cardiovascular death in patients with ES-HCM was higher than those in patients with HCM and LVEF≥50% (22/50 [44.0%] vs. 13/200 [6.5%]; 12/50 [24.0%] vs. 4/200 [2.0%], all P<0.001). Multivariate logistic regression analysis showed that the influencing factors associated with ES-HCM included age at first symptom onset (odds ratio [OR]=0.95, 95% CI [0.90, 1.00], P=0.042), New York Heart Association (NYHA) class (OR=7.73, 95% CI [2.93, 20.41], P<0.001), heart rate (OR=1.07, 95% CI [1.02, 1.12], P=0.003), QRS duration (OR=1.03, 95% CI [1.00, 1.05], P=0.020), left ventricular end-diastolic diameter (LVEDD) (OR=1.15, 95% CI [1.04, 1.28], P=0.006), left atrial anteroposterior diameter (LAD) (OR=1.13, 95% CI [1.03, 1.24], P=0.012), and maximum left ventricular wall thickness (MLVWT) (OR=0.80, 95% CI [0.68, 0.93], P=0.005). Among the 50 patients with ES-HCM, NYHA class (P<0.001) and heart rate (P=0.017) were each associated with a higher likelihood and earlier occurrence of heart transplantation or all-cause mortality in univariate analyses. The influencing factors for ES-HCM included the age at first symptom onset, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT. Both NYHA class and heart rate were related to the prognosis of ES-HCM.

Cardiac intravoxel incoherent motion diffusion-weighted imaging to assess myocardial microcirculation dysfunction in hypertension.

Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction. In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system. Hypertensive patients were divided into 3 subgroups based on blood pressure (BP) types. Two experienced CMR radiologists independently analyzed all images, and Bland-Altman analysis was applied to assess intra- and inter-observer reproducibility. Cardiac function indexes and IVIM-DWI parameters were compared between the hypertension and healthy control groups, as well as among the three hypertension subgroups. Totally 62 participants with hypertension and 27 healthy controls were included. 13 participants were excluded for poor quality of IVIM-DWI images. Significantly higher maximal left ventricular wall thickness (10.3±2.0 vs. 8.6±1.4 mm, P<0.001) and left ventricular mass index (49.0±9.1 vs. 42.1±7.5 g/m2, P<0.05) were observed inhypertension group compared with healthy control group. There were significant statistical differences in pseudo diffusion (D*) between them (81.3±16.3 vs. 111.8±18.9 mm2/s, P<0.001), as well as among the three hypertension subgroups (99.4±13.9 vs. 79.7±10.6 vs. 67.1±6.6 mm2/s, P<0.001). Participants with poor quality of IVIM-DWI images had higher heart rates (72.2±10.0 vs. 62.0±8.1 bpm, P<0.001). IVIM-DWI is feasible for quantitatively evaluating myocardial microcirculation dysfunction in hypertension. The D* parameter has a potential value for assessing the severity of microcirculation dysfunction in different BP categories.

Patterns of Left Ventricular Remodelling in Children and Young Patients with Hypertrophic Cardiomyopathy.

Introduction: The aim of this study was to evaluate the age at onset, clinical course, and patterns of left ventricular (LV) remodelling during follow-up in children and young patients with hypertrophic cardiomyopathy (HCM). Methods: We included consecutive patients with sarcomeric or non-syndromic HCM below 18 years old. Three pre-specified patterns of LV remodelling were assessed: maximal LV wall thickness (MLVWT) thickening; MLVWT thinning with preserved LV ejection fraction; and MLVWT thinning with progressive reduction in LV ejection fraction (hypokinetic end-stage evolution). Results: Fifty-three patients with sarcomeric/non-syndromic HCM (mean age 9.4 ± 5.5 years, 68% male) fulfilled the inclusion criteria. In total, 32 patients (60%) showed LV remodelling: 3 patients (6%) exhibited MLVWT thinning; 16 patients (30%) showed MLVWT thickening; and 13 patients (24%) progressed to hypokinetic end-stage HCM. Twenty-one patients (40%) had no LV remodelling during follow-up. In multivariate analysis, MLVWT was a predictor of the hypokinetic end-stage remodelling pattern during follow-up (OR 1.17 [95%CI 1.01-1.36] per 1 mm increase, p-value 0.043), regardless of sarcomeric variants and New York Heart Association class. Two patients with sarcomeric HCM, showing a pattern of MLVWT regression during childhood, experienced progression during adolescence. Conclusions: Different patterns of LV remodelling were observed in a cohort of children with sarcomeric/non-syndromic HCM. Interestingly, a pattern of progressive MLVWT thinning during childhood, with new progression of MLVWT during adolescence, was noted. A better understanding of the remodelling mechanisms in children with sarcomeric HCM may be relevant to defining the timing and possible efficacy of new targeted therapies in the preclinical stage of the disease.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = -0.403, p = 0.037) and LV stroke volume (SV) (r = -0.425, p = 0.027). MAT correlated inversely with SV (r = -0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, β = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

The CHOIR study: acute hemodynamic effects of different pacing strategies in hypertrophic obstructive cardiomyopathy

Abstract Background The majority of patients with hypertrophic cardiomyopathy present with dynamic left ventricular (LV) outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medical therapy, invasive septal reducing therapies, or pacemaker therapy. There is conflicting evidence regarding the efficacy of pacemaker therapy. The effect of pacing strategies at physical exertion has not been investigated in HOCM. Purpose To identify the optimal pacing strategy for reducing LVOTO without compromising cardiac output at rest and exercise in HOCM. Methods In this ongoing project, we have so far included eight patients with symptomatic HOCM referred to our hospital for alcohol septal ablation (ASA). The day before ASA, we placed temporary pacing leads in the right atrium, the right ventricular (RV) apex and on the LV lateral wall. We also inserted a pulmonary artery catheter and performed per operative echocardiography. All patients had sinus rhythm. Intrinsic rhythm served as baseline and was followed by atrial sensed RV pacing, LV pacing and biventricular (BiV) pacing at rest and during supine cycling. We assessed LVOTO by echocardiography, and cardiac output by the thermodilution method under intrinsic rhythm and all pacing modalities. Results The mean age was 52±15 years, and two of eight patients were female. The mean maximal LV wall thickness was 16±1 mm. The resting LVOTO was 50±23 mmHg. Due to difficulties in placing the LV lead within a reasonable time frame, complete study protocol was not performed in all patients. All eight patients performed RV pace at rest, but only five patients (63 %) were LV and BiV paced at rest. Five patients performed supine cycling but only four patients completed with RV and BiV pacing. The graphs display LVOTO and CO in sinus rhythm and the different pacing maneuvers at rest and during supine cycling. At rest, 6 out of 8 patients (75%) had LVOTO reduction during RV pace, and CO was unchanged. Four of five patients (80%) had LVOTO reduction during BiV and LV pace compared to sinus rhythm, also with unchanged CO. During supine cycling four of five patients (80%) had a reduction of the LVOTO gradient during RV and BiV pacing, without significant CO change. No complications occurred during the interventions. Conclusion In this ongoing study on cardiac pacing in HOCM, RV, LV, and BiV pacing reduced LVOTO while CO remained unchanged at rest and during exercise.

Natural history and clinical outcomes of patients with hypertrophic cardiomyopathy from thin filament mutations.

Hypertrophic cardiomyopathy (HCM) due to thick filament variants is more common; however, HCM due to thin filament variants (HCM-Thin) may be associated with a more malignant phenotype with an increased risk of sudden cardiac death. The aim of this study was to review all the published cases of HCM-Thin to better understand the natural history and clinical outcomes of this disease. A literature review of HCM-Thin identified 21 studies with a total of 177 patients that were suitable for analysis. There were three outcomes of interest, which included a heart failure composite, a ventricular arrhythmia composite and a heart failure and arrhythmia composite outcome. Kaplan-Meier (KM) survival analyses for freedom from each of the abovementioned composite outcomes were completed for the entire cohort and stratified by age of onset and sarcomeric variant. The heart failure composite occurred in 24 (13.6%) patients, the ventricular arrhythmia composite occurred in 30 patients (16.9%) and the combined heart failure and arrhythmia composite occurred in 50 patients (28.2%). In regard to left ventricular ejection fraction (LVEF), the majority of patients were preserved (LVEF>50%) compared with mildly reduced (LVEF 41%-50%) and reduced (LVEF≤40%) (respectively 26.6% vs. 0.6% vs. 3.4%). The median maximal left ventricular wall thickness (LVWT) was 19.0mm [interquartile range (IQR) 5.3]. Only 10.7% of the cohort had evidence of left ventricular outflow tract (LVOT) obstruction. Those with paediatric-onset HCM had earlier onset and were at higher risk for each endpoint than their adult counterparts. When stratified by genetic variant, patients with TNNI3 and TPM1 were at a higher risk of the heart failure composite endpoint and the combined heart failure and arrhythmia composite endpoint in comparison with those with the other genetic variants. HCM-Thin is associated with significant morbidity and mortality, with a high arrhythmia burden despite low rates of cardiac obstruction and mild hypertrophy. The paediatric onset of disease and certain sarcomeric variants appear to be associated with a worse prognosis than their adult-onset and other sarcomeric variant counterparts. HCM-Thin seems to have a distinct phenotype, which may require a different management approach.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats

BackgroundIn people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight.ResultsAt baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17–29%), with a median reduction in body fat mass of 45% (26–64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction.ConclusionAn increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and β-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with β-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Discrimination models with radiomics features derived from cardiovascular magnetic resonance images for distinguishing hypertensive heart disease from hypertrophic cardiomyopathy.

Discriminating hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging, because both are characterized by left ventricular hypertrophy (LVH). Radiomics might be effective to differentiate HHD from HCM. Therefore, this study aimed to investigate discriminators and build discrimination models between HHD and HCM using multiparametric cardiac magnetic resonance (CMR) findings and radiomics score (radscore) derived from late gadolinium enhancement (LGE) and cine images. In this single center, retrospective study, 421 HCM patients [median and interquartile range (IQR), 50.0 (38.0-59.0) years; male, 70.5%] from January 2017 to September 2021 and 200 HHD patients [median and IQR, 44.5 (35.0-57.0) years; male, 88.5%] from September 2015 to July 2022 were consecutively included and randomly stratified into a training group and a validation group at a ratio of 6:4. Multiparametric CMR findings were obtained using cvi42 software and radiomics features using Python software. After dimensional reduction, the radscore was calculated by summing the remaining radiomics features weighted by their coefficients. Multiparametric CMR findings and radscore that were statistically significant in univariate logistic regression were used to build combined discrimination models via multivariate logistic regression. After multivariate logistic regression, the maximal left ventricular end diastolic wall thickness (LVEDWT), left ventricular ejection fraction (LVEF), presence of LGE, cine radscore and LGE radscore were identified as significant characteristics and used to build a combined discrimination model. This model achieved an area under the receiver operator characteristic curve (AUC) of 0.979 (0.968-0.990) in the training group and 0.981 (0.967-0.995) in the validation group, significantly better than the model using multiparametric CMR findings alone (P<0.001). Radiomics features derived from cardiac cine and LGE images can effectively discriminate HHD from HCM.