黄静涵
中国医学科学院阜外医院 心肺功能检测中心
OBJECTIVES:The aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).BACKGROUND:Patients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated.METHODS:A total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test.RESULTS:During a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001).CONCLUSIONS:T1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.
JACC. Cardiovascular imaging 2022
Mutations in the hyperpolarization-activated nucleotide-gated channel 4 (HCN4) are known to be associated with arrhythmias in which QT prolongation (delayed ventricular repolarization) is rare. Here, we identified a HCN4 mutation, HCN4-R666Q, in two sporadic arrhythmia patients with sinus bradycardia, QT prolongation, and short bursts of ventricular tachycardia. To determine the functional effect of the mutation, we conducted clinical, genetic, and functional analyses using whole-cell voltage-clamp, qPCR, Western blot, confocal microscopy, and co-immunoprecipitation. The mean current density of HEK293T cells transfected with HCN4-R666Q was lower in 24 to 36 h after transfection and was much lower in 36 to 48 h after transfection relative to cells transfected with wildtype HCN4. Additionally, we determined that the HCN4-R666Q mutant was more susceptible to ubiquitin-proteasome system-mediated protein degradation than wildtype HCN4. This decreased current density for HCN4-R666Q could be partly rescued by treatment with a proteasome inhibitor. Therefore, we conclude that HCN4-R666Q had an effect on HCN4 function in two aspects, including decreasing the current density of the channel as a biophysical effect and weakening its protein stability. Our findings provide new insights into the pathogenesis of the HCN4-R666Q mutation.
The Journal of biological chemistry 2022
BACKGROUND:Patients who have unexplained giant T-wave inversions but do not meet criteria for hypertrophic cardiomyopathy (HCM) (left ventricular (LV) wall thickness < 1.5 cm) demonstrate LV apical morphological features that differ from healthy subjects. Currently, it remains unknown how the abnormal LV apical morphology in this patient population changes over time. The purpose of this study was to investigate LV morphological and functional changes in these patients using a mid-term cardiovascular magnetic resonance (CMR) exam.METHODS:Seventy-one patients with unexplained giant T-wave inversion who did not fulfill HCM criteria were studied. The mean interval time of the follow-up CMR was 24.4 ± 8.3 months. The LV wall thickness was measured in each LV segment according to the American Heart Association 17-segmented model. The apical angle (ApA) was also measured. A receiver operating curve (ROC) was used to identify the predictive values of the CMR variables.RESULTS:Of 71 patients, 16 (22.5%) progressed to typical apical HCM, while 55 (77.5%) did not progress to HCM criteria. The mean apical wall thickness was significantly different between the two groups at both baseline and follow-up, with the apical HCM group having greater wall thickness at both time points (all p < 0.001). There was a significant difference between the two groups in the change of ApA (- 1.5 ± 2.7°/yr vs. - 0.7 ± 2.0°/yr, p < 0.001) over time. The combination of mean apical wall thickness and ApA proved to be the best predictor for fulfilling criteria for apical HCM with a threshold value of 8.1 mm and 90° (sensitivity 93.8%, specificity 85.5%).CONCLUSIONS:CMR metrics identify predictors for progression to HCM in patients with unexplained giant T-wave inversion.
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 2021
BACKGROUND:As the paucity of data focusing on evaluating cardiac structure and function in patients with or without gene mutation, this study was sought to investigate the correlation between genotype and cardiac magnetic resonance (CMR) phenotype in patients with left ventricular non-compaction cardiomyopathy (LVNC) and to explore prognostic relevance in this cohort if possible.METHODS:Patients with LVNC who underwent CMR and targeted gene sequencing between 2006 and 2016 were retrospectively evaluated. Demographic data, clinical presentation, genetic analysis, CMR data and follow-up data of all participants were collected.RESULTS:Compared to negative genotype (G-) group, patients with positive genotype (G+) had larger left atrial volume (LAV), and carriers of multiple variants had lower left ventricular (LV) ejection fraction and cardiac index, increased LV fibrosis, larger LA volume, reduced LV global circumferential strain, LA reservoir strain and booster pump strain (all p < 0.05). LA volume was able to discriminate patients with G + (all p < 0.05), as well as those with multiple genetic mutation (all p < 0.01). During a median follow-up of 5.1 years, Kaplan-Meier survival analysis revealed worse primary endpoint-free survival among carriers of multiple variants compared to G- group.CONCLUSIONS:CMR feature tracking is a remarkable tool to evaluate implication, genetics cascade screen and predict outcome in LVNC population. LA volume is a sensitive and robust indicator for genetic mutational condition, of which facilities to guide clinical management and intensity of follow-up for patients and their relatives.
Insights into imaging 2021
PURPOSE:To investigate the MRI characteristics, prevalence, and outcomes of hypertrophic cardiomyopathy (HCM) with restrictive phenotype.MATERIALS AND METHODS:A total of 2592 consecutive patients with HCM were evaluated to identify individuals who fulfilled the diagnostic criteria of restrictive phenotype. Thirty-four patients with HCM (mean age, 41 years ± 16 [standard deviation]; range, 21-62 years, 16 men) with restrictive phenotype were retrospectively identified. Thirty-four patients with HCM with the same age and sex distributions were randomly selected as a control group. Kaplan-Meier survival curves were compared using log-rank statistics for survival analysis.RESULTS:The anteroposterior diameters of the left and right atria were 55 mm ± 5 and 61 mm ± 9, respectively, which were larger than those of the control group (P < .001). The maximum wall thickness in the restrictive group was lower than that in the control group (16 mm ± 2 vs 19 mm ± 3, P < .001). No significant difference was found in late gadolinium enhancement fraction between the restricted phenotype and the control group (15% ± 8 vs 13% ± 7, P = .376). The 5-year event-free survival from any cause of death and cardiac transplantation was 81% in the restrictive group, compared with 94% in the control group (log-rank P = .018).CONCLUSION:Restrictive phenotype is a rare subtype of HCM and is associated with severe clinical symptoms and poor prognosis. The MRI features of this phenotype include mild to moderate left ventricular hypertrophy, markedly enlarged atria, moderate myocardial fibrosis, and pericardial effusion.© RSNA, 2020.
Radiology. Cardiothoracic imaging 2020
Background The value of native myocardial T1 mapping and extracellular volume (ECV) fraction in patients who have hypertrophic cardiomyopathy (HCM) but no late gadolinium enhancement (LGE) and no hemodynamic obstruction are currently unknown. Purpose To evaluate myocardial fibrosis in patients with nonobstructive HCM and no LGE by using native myocardial T1 mapping and ECV fraction and to study their relationships to left ventricular (LV) function and LV hypertrophy. Materials and Methods Patients with HCM who underwent cardiac MRI between 2012 and 2015 were retrospectively evaluated. Patients were included if they had no LGE at MRI, LV ejection fraction greater than or equal to 45%, and no LV outflow tract obstruction. Healthy participants had similar age and sex distribution. Native myocardial T1 and ECV were measured with MRI. Results A total of 258 patients with HCM (mean age ± standard deviation, 49 years ± 15; 74% men) and 122 healthy participants (mean age, 50 years ± 14; 76% men) were evaluated. Native myocardial T1 was longer and ECV fraction was higher in the patients with HCM relative to the healthy participants (mean native T1, 950 msec ± 48 vs 913 msec ± 46; mean ECV, 24.5% ± 2.8 vs 23.0% ± 2.7; both P < .001). Maximum T1 and ECV values correlated strongly with LV mass index for the entire patient cohort with HCM (both r = 0.86; P < .001) and for the subgroups (r = 0.86 and 0.85 for interventricular septal group and r = 0.88 and 0.86 for apical group; all P < .001). Conclusion Prolonged myocardial T1 and elevated extracellular volume in hypertrophic cardiomyopathy suggests diffuse myocardial fibrosis, even in the absence of regionally apparent late gadolinium enhancement and hemodynamic obstruction, and is associated with left ventricular hypertrophy. © RSNA, 2019 See also the editorial by Bluemke and Lima in this issue.
Radiology 2020
The clinical features, CMR characteristics and outcomes of arrhythmogenic left ventricular cardiomyopathy (ALVC), which is a very rare nonischemic cardiomyopathy, are currently not well studied. The purpose of the study is to investigate the clinical and cardiovascular magnetic resonance (CMR) imaging characteristics of arrhythmogenic left ventricular cardiomyopathy (ALVC). Fifty-three consecutive patients with ALVC were divided into two groups: ALVC patients without right ventricular (RV) involvement (n = 36, group 1) and those with RV involvement (n = 17, group 2). Clinical symptoms, cardiac electrophysiological findings, and CMR parameters (morphology, ventricular function, and myocardial fibrosis and fatty infiltration) were evaluated in both groups. The two groups showed no significant difference in age, gender, or presenting symptoms (P > 0.05). Right bundle branch block ventricular arrhythmia was less common in patients without RV involvement (50.0% vs.64.7%, P = 0.031). There were no significant differences in left ventricular function between the two groups, however right ventricular ejection fraction was significantly lower in group 2 (40.1 ± 4.0% vs. 48.7 ± 3.9%, P < 0.001). Inverse correlations of left ventricular ejection fraction with fat volume (r = -0.883, p = 0.001), late gadolinium enhancement (LGE) volume (r = -0.892, 0.013), ratio of fat/LGE (r = -0.848, p < 0.001), indexed left ventricular end diastolic volume (r = -0.877, p < 0.001) and indexed left ventricular end systolic volume (r = -0.943, p < 0.001) were all significant. ALVC is a rare disease with fibro-fatty replacement predominantly in the left ventricle, impaired left ventricular systolic function, and ventricular arrhythmias originating from the left ventricle. ALVC with right ventricular involvement may have a worse prognosis.
Scientific reports 2020
AIMS:Patients with unexplainable giant T-wave inversion in the precordial leads and apical wall thickness <15 mm have been reported. These patients cannot be diagnosed as apical hypertrophic cardiomyopathy (AHCM) according to the current criteria. The objective of this study was to evaluate the apical morphological features of this type of patients using cardiac magnetic resonance.METHODS AND RESULTS:Institutional ethics approval and written informed consent were obtained. A total of 60 subjects with unexplainable giant T-wave inversion and 76 healthy volunteers were prospectively enrolled in the study. The segmented left ventricular (LV) wall thickness was measured according to the American Heart Association 17-segmented model. The apical angle (apA) as well as the regional variations in LV wall thickness was analysed. Considerable variation in LV wall thickness in normals was observed with progressive thinning from the base to apex (male and female, P < 0.01). The apical thickness of subjects with giant T-wave inversion was 8.10 ± 1.67 mm in male, which is thicker than that of controls (4.14 ± 1.17 mm, P < 0.01). In female, the apical thickness was also significantly different from controls (5.85 ± 2.16 vs. 2.99 ± 0.65 mm, P < 0.01). Compared with normals, the apA decreased significantly in male (87.44 ± 13.86 vs.115.03 ± 9.90°, P < 0.01) and female (90.69 ± 8.84 vs. 110.07 ± 13.58°, P < 0.01) subjects, respectively.CONCLUSION:Although the absolute thickness of apical wall was below the current diagnostic criteria of AHCM, the apical morphological features of subjects with unexplainable giant T-wave inversion were significantly different from normals. Whether these subjects should be included into a preclinical scope of AHCM needs further investigations.
European heart journal. Cardiovascular Imaging 2017
BACKGROUND:Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required.METHODS AND RESULTS:One-hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient ≥50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased ≥50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment (r=0.371; P<0.001), basal anteroseptal segment (r=0.527; P<0.001), and total thickness of the above 2 segments (r=0.672; P<0.001). The area under the receiver operating curves were 0.68, 0.79 and 0.89 for predictive analysis (all P<0.001). The cutoff thickness of the segment 1+2 was 50.9 mm, which yielded a sensitivity of 86% and specificity of 77%.CONCLUSIONS:Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA.
Circulation. Cardiovascular interventions 2016
UNLABELLED:Due to similar manifestations of hypertensive ventricular walls and abnormal ventricular compliance, it is difficult to differentiate cardiac amyloidosis (CA) and nonobstructive hypertrophic cardiomyopathy (NOHCM) clinically. The purpose of the study was to investigate the value of electrocardiography (ECG) in the differentiation of the two diseases.METHODS:We enrolled 46 consecutive patients with CA and 64 patients with NOHCM and compared their ECG characteristics.Compared with NOHCM patients, the ECG of CA patients showed more low voltage on limb leads (50% versus 1.6%), atrioventricular block (21.7% versus 4.7%), pseudo-infarct pattern (84.8% versus 39.1%), and longer QRS duration (104 ± 25 versus 98 ± 14 ms) (all P < 0.05). The QRS complex voltage of avR demonstrated the highest diagnostic performance (sensitivity 89%, specificity 94%, cut-off value 0.45mV) as assessed by ROC analysis. The combination of the R wave voltage of I and avR reached a sensitivity of 95% and a specificity of 87% for the diagnosis of amyloidosis.Compared with NOHCM patients, CA patients showed more ECG characteristics of low voltage on limb leads, pseudo-infarct pattern, atrioventricular block, and longer QRS duration. The combination of the R wave voltage of I, avR, and QRS was of diagnostic value in the differentiation of CA from NOHCM.
International heart journal 2015
