Comparison of clinical, morphological, and prognostic features in hypertrophic cardiomyopathy between Japanese and western patients

Apical hypertrophic cardiomyopathy appears to be more common in Japan than in the West. Explanations for this difference include variable methods and criteria for the diagnosis. To assess morphological, clinical, and prognostic differences, 45 consecutive Japanese and 45 age- and gender-matched Western patients with hypertrophic cardiomyopathy were evaluated in two referral institutions by the same individuals. The diagnosis of hypertrophic cardiomyopathy was based on the echocardiographic demonstration of unexplained left ventricular hypertrophy. Patients were aged 8 to 64 years (mean 50); there were 66 males and 24 females. The pattern of left ventricular hypertrophy was similar in Japanese and Western patients: asymmetric septal 64 vs. 76%, concentric 22 vs. 13%, and apical 13 vs. 11% (p = NS). The incidence of an echocardiographic or Doppler calculated left ventricular gradient of > 30 mmHg was similar (11 vs. 18%; p = NS). The maximal left ventricular wall thickness was greater in Western patients (23 +/- 7 vs. 20 +/- 4 mm; p = 0.03), but was not different when adjusted for body surface area. Clinical features including incidence of family history and ventricular tachycardia during 24-h ambulatory electrocardiography were similar. During follow-up (4.9 +/- 4.0 years for Western vs. 4.4 +/- 2.0 years for Japanese), disease-related mortality was worse in Western patients (p < 0.05; 10 versus 2 patients). This evaluation, using the same diagnostic methods and criteria, reveals a worse prognosis in Western patients despite a similar clinical and morphological spectrum of hypertrophic cardiomyopathy.     

The effect of beta-adrenergic blockade in dilated cardiomyopathy — a questionnaire study in Japan

The effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 ± 20.4 mg, mean ± SD), propranolol (four patients, 26.3 ± 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P < 0.01).=" the=" mean=" cardiothoracic=" ratio=" decreased=" from=" 55.6%=" to=" 52.1%=">P < 0.01).=" the=" mean=" ejection=" fraction=" of=" the=" left=" ventricle=" measured=" by=" echocardiogram=" increased=" from=" 30.4%=" to=" 36.9%=">P < 0.01).=" exercise=" tolerance=" in=" the=" treadmill=" test=" improved=" significantly.=" there=" was=" no=" change=" in=" blood=" pressure,=" nor=" were=" there=" arrhythmias=" seen=" on=" holter=" electrocardiograms.=" in=" two=" patients,=" congestive=" heart=" failure=" deteriorated=" after=" administration=" of=" beta-blockers.=" it=" is=" concluded=" that=" beta-adrenergic=" blockade=" has=" a=" beneficial=" effect=" in=" most=" of=" the=" patients=" with=" dilated=">This work was supported in part by a research grant from the Ministry of Health and Welfare and by a grant-in-aid for scientific research on priority areas and for general scientific research from the Ministry of Education, Science, and Culture, Japan, and Kanazawa Research Fund.     

Whole exome sequencing analysis of 6 children with dilated cardiomyopathy北大核心CSCD

Objective To explore the mutational loci associated with the occurrence of dilated cardiomyopathy (DCM). Methods Six children with DCM and 3 healthy children were recruited through the " Children DCM Susceptibility Gene Research Project" for a prospective study from December 2019 to June 2021. Six patients were aged from 4 months to 14 years, including 5 girls and 1 boy. Three healthy children were aged between 3-13 years, including 2 girls and 1 boy. Whole exome sequencing was performed on the research subjects, and the pathogenic genes were identified by bioinformatics methods. At the same time, the venous blood of the first - degree relatives of the corresponding children was collected, and the region with gene mutations was subjected to next - generation sequencing. Results A total of 4 mutational loci that might be related to DCM were identified. Case 1 was found to have a c. 2011-3C > G mutation in the jounctophiilin - 2 (JPH2) gene. The c. 2011-3 C > G mutation was homozygous (GG) in the child, but heterozygous (CG) in the parents. This child also had a c. G49415A mutation in the titin (TTN) gene. This c. G49415A mutation was homozygous (AA) in the child, but heterozygous (GA) in the parents. Case 4 was found to have a c. G23033A mutation in the TTN gene. The c. G23033A mutation was heterozygous (GA) in both the subject and the father, but a wild type (GG) in the mother. Case 5 was found to have a c. 16975_16978del mutation in the TTN gene. The c. 16975_16978del mutation was heterozygous (TCTTC/T) in the child and the father, but a wild type (TCTTC/TCTTC) in the mother. Conclusions A total of 4 pathogenic gene loci related to the pathogenesis of DCM are identified in this study. The finding enriches the DCM disease gene spectrum and provides targets for the implementation of precision medicine. © 2022 ＣｈｉｎＪＡｐｐｌＣｌｉｎＰｅｄｉａｔ. All rights reserved.     

不同病因心衰患者血浆脑钠素水平的影响

目的　观察不同病因心衰患者血浆脑钠素(BNP)水平的变化 ,探讨BNP在心衰发病机制中所起的作用以及 β -受体阻滞剂对心衰患者BNP水平的影响。 方法　采用酶联免疫吸附试验 (ELISA)法测定心衰患者血浆BNP水平。结果　心衰组BNP水平与正常对照组相比显著升高(P <0 0 1)。重度心衰心功能Ⅲ、Ⅳ级BNP水平明显高于心功能Ⅱ级。BNP变化的幅度在冠心病、扩张型心肌病不同病因心衰中有所不同 ,冠心病心衰BNP水平升高更明显 (P <0 0 1)。心衰患者中常规治疗组与非 β -受体阻滞剂治疗组相比 ,美托洛尔和卡维地洛治疗组BNP水平明显降低 (P <0 0 5 )。结论　心衰患者血浆BNP水平显著升高 ,BNP水平与心衰严重程度呈正相关 ,冠心病心衰BNP水平较扩张型心肌病组明显升高 ,提示冠心病心肌缺血损伤可能进一步促进BNP分泌。美托洛尔和卡维地洛均能下调心衰BNP水平 ,可能是不同β -受体阻滞剂逆转心衰神经激素过度激活的共同作用机制之一。     

Prognostic Value of Global Longitudinal Strain in Hypertrophic Cardiomyopathy: A Systematic Review of Existing Literature

ObjectivesThe association of left ventricular global longitudinal strain (LV-GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has been examined in multiple studies. The authors conducted a systematic review aimed at summarizing and critically appraising the current evidence.BackgroundHCM is a common genetic cardiovascular disease with an estimated prevalence of 1 in 500 patients. LV-GLS derived from speckle tracking echocardiography is a sensitive noninvasive method of assessing regional left ventricular function. Several studies have suggested association of abnormal LV-GLS with outcomes in HCM patients.MethodsA computerized literature search of all English language publications in the PubMed and EMBASE databases was made looking at all randomized and nonrandomized studies conducted on patients with HCM where association of LV-GLS with clinical outcomes was studied. We then manually searched the reference lists of included articles. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting systematic reviews was used.ResultsOur search yielded a total of 14 observational studies published between 2009 and 2017 with a total of 3,154 patients with HCM. Eleven of the 14 studies included a composite cardiac outcome which included mortality as their primary outcome of interest and 3 of the 14 studies looked at association of LV-GLS with ventricular arrhythmias and/or implantable cardiac defibrillator discharge. We noted wide variability in inclusion, methodology, follow-up, and consequently effect estimates, which was not conducive to performing a meta-analysis. However, despite the variation, all studies revealed a degree of association of abnormal LV-GLS with poor cardiac outcomes.ConclusionsOur systematic review of more than 3000 HCM patients suggests an association of abnormal LV-GLS with adverse composite cardiac outcomes and ventricular arrhythmias.     

Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

ObjectivesThe aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality.BackgroundThe clinical significance of LA involvement in ATTR-CM is of great clinical interest.MethodsCongo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other).ResultsThere was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation.ConclusionsThe phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis.     

Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy

Background: Iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by ¹²³I-MIBG cardiac scintigraphy, whereas abnormal ¹²³I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. Hypothesis: Based on evidence from recent studies, it can be hypothesized that ¹²³I-MIBG uptake is related to histopathologic changes in the myocardium. Methods: The relation of ¹²³I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The ¹²³I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The ¹²³I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. Results: All of the global, mean, and biopsy region scores for ¹²³I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the ¹²³I-MIBG uptake scores. Conclusion: These results indicate that ¹²³I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.