Regression of Left Ventricular Hypertrophy in a Case of Sarcomeric Hypertrophic Cardiomyopathy: An Unexpected Outcome.
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SUBMITTER: Cabrera Borrego E
PROVIDER: S-EPMC8302042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsObstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic obstruction of the left ventricular (LV) outflow tract (LVOT). Although this may be mediated by interplay between the hypertrophied septal wall, systolic anterior motion of the mitral valve, and papillary muscle abnormalities, the mechanistic role of LV shape is still not fully understood. This study sought to identify the LV end-diastolic morphology underpinning oHCM.Methods and resultsCardiovascular magnetic resonance images from 2398 HCM individuals were obtained as part of the NHLBI HCM Registry. Three-dimensional LV models were constructed and used, together with a principal component analysis, to build a statistical shape model capturing shape variations. A set of linear discriminant axes were built to define and quantify (Z-scores) the characteristic LV morphology associated with LVOT obstruction (LVOTO) under different physiological conditions and the relationship between LV phenotype and genotype. The LV remodelling pattern in oHCM consisted not only of basal septal hypertrophy but a combination with LV lengthening, apical dilatation, and LVOT inward remodelling. Salient differences were observed between obstructive cases at rest and stress. Genotype negative cases showed a tendency towards more obstructive phenotypes both at rest and stress.ConclusionsLV anatomy underpinning oHCM consists of basal septal hypertrophy, apical dilatation, LV lengthening, and LVOT inward remodelling. Differences between oHCM cases at rest and stress, as well as the relationship between LV phenotype and genotype, suggest different mechanisms for LVOTO. Proposed Z-scores render an opportunity of redefining management strategies based on the relationship between LV anatomy and LVOTO.
| S-EPMC10229266 | biostudies-literature
Project description: Not available
| S-EPMC10715936 | biostudies-literature
Project description:The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM).Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging.In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement.There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. -5% [-11% to -0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% ± 26% with placebo vs. -23% ± 45% with losartan; p = 0.03).This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461).
| S-EPMC3950308 | biostudies-literature
Project description:AimsIdiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM.Methods and resultsFamilies of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family.ConclusionIdiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.
| S-EPMC7132543 | biostudies-literature
Project description:BackgroundDiagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated.MethodsWe performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients.ResultsOf the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio >1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2.ConclusionA cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria.
| S-EPMC4392393 | biostudies-literature
Project description:The noninvasive assessment of altered myocardium in patients with genetic mutations that are associated with hypertrophic cardiomyopathy (HCM) remains challenging. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy. We studied 3 groups of genotyped individuals: sarcomere mutation carriers with left ventricular hypertrophy (clinical HCM; n=36), mutation carriers with normal left ventricular wall thickness (subclinical HCM; n=28), and healthy controls (n=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including cardiac magnetic resonance measures of interstitial fibrosis (extracellular volume fraction), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation-adjusted analyses, the SIC was quantitatively different across subjects with overt HCM, subclinical HCM, and healthy controls (P<0.001). Compared with controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (P<0.001 for both). The SIC was significantly correlated with extracellular volume (r=0.72; P<0.01), with left ventricular mass and E' velocity (r=0.45, -0.60, respectively; P<0.01 for both), and with serum NTproBNP levels (r=0.36; P<0.001). Our findings suggest that the SIC could serve as a noninvasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and to evaluate the effects of interventions.
| S-EPMC5024718 | biostudies-literature
Project description: Not available
| S-EPMC8307343 | biostudies-literature
Project description:Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV).Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH-, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH- mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH-, controls, respectively; P?0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58; P<0.001) and global E' velocity (r=-0.48; P<0.001). Late gadolinium enhancement was present in >60% of overt patients with HCM but absent from G+/LVH- subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM.Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis.
| S-EPMC3769196 | biostudies-literature
Project description:Left ventricular hypertrophy (LVH) typically manifests during or after adolescence in sarcomere mutation carriers at risk for developing hypertrophic cardiomyopathy. Guidelines recommend serial imaging of mutation carriers without LVH (G+/LVH-) to monitor for phenotypic evolution, but the optimal strategy is undefined. Compared with echocardiography (echo), cardiac MRI (CMR) offers improved endocardial visualization and potential to assess scar. However, the incremental advantage offered by CMR for early diagnosis of hypertrophic cardiomyopathy is unclear. Therefore, we systematically compared echo and CMR in G+/LVH- subjects.A total of 40 sarcomere mutation carriers with normal echo wall thickness (<12 mm or z score <2.5 in children) underwent concurrent CMR. Mean age was 21.7±11.1 years, 55% were female. If left ventricular wall thickness seemed nonuniform, the size and location of relatively thickened segments were noted. Late gadolinium enhancement was assessed with CMR. Diagnostic agreement between echo and CMR was good (90%), although CMR measurements of left ventricular wall thickness were ?19% lower than echo. Four subjects had mild hypertrophy (12.6-14 mm; ?2 segments) appreciated by CMR but not echo. No subjects had late gadolinium enhancement. During median 35-month follow-up, 2 subjects developed overt hypertrophic cardiomyopathy, including 1 with mild LVH by CMR at baseline.Echo is unlikely to miss substantial LVH; however, CMR identified mild hypertrophy in ?10% of mutation carriers with normal echo wall thickness. CMR may be a useful adjunct in hypertrophic cardiomyopathy family screening, particularly in higher risk situations, or if echocardiographic images are suboptimal or suggest borderline LVH.
| S-EPMC3974911 | biostudies-literature
Project description:Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.
| S-EPMC2607563 | biostudies-literature