Clinical and genetic characteristics of different types of non-obstructive hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To analyze the clinical and genetic characteristics of clinical subtypes of non-obstructive hypertrophic cardiomyopathy (HCM). Methods: It was a cohort study. Patients with non-obstructive HCM admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, from January 1999 to April 2019 were enrolled. According to the characteristics of cardiac morphology and function shown by echocardiography, the patients were divided into common type, dilated type, restricted type and reduced ejection fraction type. The clinical data of the patients were recorded, and 8 sarcomere pathogenic genes were screened by full exon sequencing or panel sequencing. Patienst were followed up and cardiovascular endpoint events were recorded. Results: A total of 815 patients with non-obstructive HCM were enrolled, including 27 (3.3%) restricted type, 51 (6.3%) dilated type, 30 (3.7%) reduced ejection fraction type and 707 (86.7%) common type. A total of 704 out of 815 patients underwent genetic testing. Among them, 299 (42.5%) patients carried at least 1 sarcomere gene mutation. MYBPC3 and MYH7 mutation accounted for 42.1% (126/299) and 35.8% (107/299) respectively. 66.7% (16/24) of the patients with restricted type carried sarcomere gene mutation, which was higher than that in patients with dilated type (36.4% (16/44)) and in common type (41.5% (250/602), P=0.015). Among the patients with reduced ejection fraction, 56.7% (17/30) patients carried sarcomere gene mutations, 23.3% (7/30) carried multiple sarcomere mutations, which was higher than that in restricted type (8.3% (2/24)), in dilated type (9.1% (4/44)) and in common type 4.2% ((24/577), P<0.001). MYH7 and MYBPC3 were the main mutation gene types of all clinical subtypes, and the genotypes were similar among groups (all P>0.05). Seven hundred and three out 815 patients were followed up for 2.9 (1.4, 4.0) years. There were 53(7.5%) cardiovascular death. Cardiovascular death occurred in 5.0% (29/578) patients with common type, 13.0% (3/23) patients with restricted type, 16.3% (7/43) patients with dilated type and 46.7% (14/30) patients with decreased ejection fraction. Univariate Cox proportional hazards model analysis showed that the risk of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type was higher than that in patients with common type (P<0.001). After adjusting for gender, age of onset, body mass index, history of hypertension, coronary heart disease and diabetes, multivariate Cox proportional hazards model analysis showed that the HR of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type were 5.454 (95%CI 1.137-26.157, P=0.034) and 6.597 (95%CI 1.632-26.667, P=0.008) and 9.028 (95%CI 2.201-37.039, P=0.002) respectively, as compared to patients with common type. Conclusions: Most of the patients with non-obstructive HCM are common type, featured by mild clinical manifestations and good prognosis. Although the proportion of restricted type and dilated type is relatively low, and cardiac systolic function is mostly preserved, the clinical phenotype and prognosis of these patients are similarly severe and poor as patients with reduced ejection fraction. The genotypes are similar in different clinical subtypes, but the proportion of patients with sarcomere gene mutation is higher in restricted type, and the proportion of patients with multiple sarcomere gene mutation is higher in decreased ejection fraction type.

Short-term prognosis and risk factors of ventricular septal rupture following acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the short-term prognosis and risk factors of ventricular septal rupture (VSR) following acute myocardial infarction (AMI).</p><p><b>METHODS</b>A total of 70 consecutive VSR patients following AMI hospitalized in our hospital from January 2002 to October 2010 were enrolled in this study. We compared the clinical characteristics of patients with VSR who survived ≤ 30 days (n = 39) and survived > 30 days (n = 31) post AMI. A short-term prognosis index of VSR (SPIV) was established based on the logistic regression analysis.</p><p><b>RESULTS</b>The single factor analysis showed that the risk factors of death within 30 days of VSR patients were female, anterior AMI, Killip class 3 or 4, apical VSR and non-aneurysm (all P < 0.05). Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for death within 30 days post VSR. Patients with SPIV ≥ 9 were associated with high risk [77.4% (24/31)] of dying within 30 days post AMI. SPIV ≤ 8 were associated with low risk as the 30 days mortality is 28.6% (8/28).</p><p><b>CONCLUSION</b>Female gender, anterior AMI, non-aneurysm, non-diabetes, Killip class 3 or 4 and time from AMI to VSR less than 4 days are independent risk factors of short-term mortality of VSR.</p>

Clinical analysis and risk stratification of ventricular septal rupture following acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ventricular septal rupture (VSR) remains an infrequent but devastating complication of acute myocardial infarction (AMI). The best time to undergo surgical repair is controversial and there is currently no risk stratification for patients with VSR to guide treatment. The purpose of this study was to review the clinical outcomes of 70 patients with VSR, to analyze the short-term prognosis factors of VSR following AMI, and to make a risk stratification for patients with VSR.</p><p><b>METHODS</b>A total of 70 consecutive VSR patients following AMI treated in our hospital from January 2002 to October 2010 were enrolled in this study retrospectively. The difference of clinical characteristics were observed between patients with VSR who survived ≤30 days and survived >30 days. We analyzed the short-term prognosis factors of VSR and established the short-term prognosis index of VSR (SPIV) based on the Logistic regression analysis to stratify patients with VSR.</p><p><b>RESULTS</b>Among 12 354 patients with acute ST-segment elevation myocardial infarction, 70 (0.57%) patients (33 males and 37 females) were found to have VSR. The average age was (68.1±8.5) years. Fifty-four (77.1%) patients were diagnosed with an acute anterior infarction. Patients with VSR selected for surgical repair had better outcomes than patients treated conservatively; 1-year mortality 9.5% versus 87.8%, P < 0.005. Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-ventricular aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for shortterm mortality. SPIV ≥9 indicates a high risk as the 30-day mortality is 77.4%; SPIV <8 indicates a low risk as the 30-day mortality is 28.6%; SPIV between 8 and 9 indicates a moderate risk.</p><p><b>CONCLUSIONS</b>VSR remains a rare but devastating complication of AMI. The independent risk determinants for short-term mortality of VSR were female gender, anterior AMI, non-ventricular aneurysm, non-diabetes, Killip class 3 or 4, and the time from AMI to VSR less than 4 days. It is reasonable to take more active treatments for the patients at high risk to save more lives.</p>

Mid-ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm and sustained ventricular tachycardia: a case report and literature review / 中华医学杂志(英文版)

The case is a 54-year-old man with hypertrophic cardiomyopathy, mid-ventricular obstruction, apical aneurysm, and recurrence sustained monomorphic ventricular tachycardia (VT). A coronary angiogram revealed myocardial bridging located in the middle of the left anterior descending coronary artery (LAD), and the left ventriculogram showed an hour-glass appearance of the left ventricular cavity. There was a significant pressure gradient of 60 mmHg across the mid-ventricular obliteration at rest. A successful myectomy of the inappropriate hypertrophy myocardium and excision of the apical aneurysm were performed. Pathologic analysis demonstrated fibrosis in the apical aneurysm and thickened and narrowed vessels in the adjacent area. During the follow-up of eighteen months, the patient remained clinically stable and free from arrhythmic recurrence.

Incidence of coronary artery disease and outcome of patients with left ventricular noncompaction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the incidence of coronary artery disease (CAD) and outcome of patients with left ventricular noncompaction (LVNC).</p><p><b>METHODS</b>Fifty-one patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January 2006 to August 2010 were retrospectively reviewed. Coronary angiography or MDCT was performed for detecting coronary artery disease. Predictors of the cardiac events were analyzed by Cox regression analysis.</p><p><b>RESULTS</b>There were 31 LVNC patients without CAD and 20 LVNC patients with CAD including single vessel coronary disease in 9 cases, double vessel coronary disease in 3 cases, three vessel coronary disease in 5 cases and left main coronary disease in 3 cases. Coronary artery bypass graft and percutaneous coronary intervention (PCI) were performed in 4 patients. Compared to LVNC patients without CAD, mean age (P = 0.008), incidence of hypertension (65.0% vs. 19.4%, P = 0.001), diabetes mellitus (40.0% vs. 12.9%, P = 0.026) and hyperlipidemia (55.0% vs. 25.8%, P = 0.035) were significantly higher while NT-proBNP level was significantly lower (P = 0.049) in LVNC patients with CAD. Incidence of major cardiac events was similar in LVNC patients with or without CAD. LogNT-proBNP is the independent prognostic factor for adverse cardiac events in patients with LVNC (HR 3.993, 95%CI 1.140 - 13.988, P = 0.030).</p><p><b>CONCLUSIONS</b>Coronary artery disease is common in patients with LVNC and associated with traditional risk factors for CAD. Poor prognosis is associated with increased NT-proBNP but not with CAD in this patient cohort.</p>

Predictive value of admission amino-terminal pro-B-type natriuretic peptide on in-hospital mortality in patients with decompensated heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the predictive value of admission plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) on in-hospital mortality in patients with decompensated heart failure.</p><p><b>METHODS</b>Plasma NT-proBNP levels were measured in patients with decompensated heart failure within 24 hours after admission with ELISA method. The NT-proBNP levels were compared between survivals and dying patients in hospital. ROC analyses were performed to evaluate the predictive value of admission plasma NT-proBNP on in-hospital mortality and to identify the optimal NT-proBNP cut-point for predicting in-hospital mortality. A binary logistic regress analyses was used to evaluate if NT-proBNP was an independent predictor for in-hospital mortality.</p><p><b>RESULTS</b>A total of 804 patients with decompensated heart failure were enrolled in his study (293 valvular heart diseases, 219 ischemic cardiomyopathy, 141 dilated cardiomyopathy, 14 hypertrophic cardiomyopathy, 21 restrictive cardiomyopathy, 39 hypertensive heart disease, 41 chronic pulmonary heart disease and 36 adult congenital heart disease) and 96 patients were in class II, 450 in class III and 258 in cases IV according to NYHA Classification. During hospitalization, 64 deaths were recorded and the on admission plasma NT-proBNP levels of patients died during hospitalization were significantly higher than those of survivals [4321.1 (3063.8, 6606.5) pmol/L vs. 1921.6 (873.9, 3739.2) pmol/L, P<0.01]. Area under receiver operating characteristic curve (AUC) of NT-proBNP to predict in-hospital death was 0.772 (95% CI: 0.718 - 0.825, P<0.01), the optimal plasma NT-proBNP cut-point for predicting in-hospital mortality was 3500 pmol/L, with a sensitivity of 70.3%, a specificity of 72.0%, an accuracy of 71.9%, a positive predictive value of 17. 8% and a negative predictive value of 96.6%. Patients whose NT-proBNP levels were equal or more than 3500 pmol/L had a much higher in-hospital mortality (17.8%) compared with those with NT-proBNP levels of less than 3500 pmol/L (3.4%), P<0.01. Binary logistic regress analyses demonstrated that admission plasma NT-proBNP, pneumonia, heart rate and NYHA class were independent predictors for in-hospital mortality in patients with decompensated heart failure (P<0.05 or 0.01) and admission plasma NT-proBNP was the strongest predictor for in-hospital mortality.</p><p><b>CONCLUSIONS</b>Admission plasma NT-proBNP level was an independent predictor for in-hospital mortality in patients with decompensated heart failure. The optimal NT-proBNP cut-point for predicting in-hospital mortality was 3500 pmol/L in this patient cohort.</p>

Association of plasma amino-terminal pro-A-, B- and C-type natriuretic peptide levels with NYHA grade and echocardiographic derived parameters of cardiac function in heart failure patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the correlation of plasma amino-terminal pro-A-, B- and C-type natriuretic peptide (NT-proANP, NT-proBNP and NT-proCNP) levels with New York Heart Association (NYHA) functional class and echocardiographic derived parameters of cardiac function in heart failure patients.</p><p><b>METHODS</b>Data of NYHA grade, echocardiographic derived parameters of cardiac function, plasma levels of NT-proANP, NT-proBNP and NT-proCNP (measured by enzyme immunoassay method) were obtained in 112 heart failure patients and 44 normal control subjects. The correlation analysis was made between NT-proANP, NT-proBNP, NT-proCNP and NYHA functional class, left atrium diameter (LAD), left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF), respectively.</p><p><b>RESULTS</b>The plasma concentrations of NT-proANP, NT-proBNP and NT-proCNP in heart failure patients were significantly higher than in control group (all P<0.05). Correlation analysis revealed a strong correlation between NT-proANP and NT-proBNP (r = 0.790, P = 0.000) and a weak correlation between NT-proCNP and NT-proBNP (r = 0.278, P = 0.003) as well as between NT-proCNP and NT-proANP (r = 0.236, P = 0.012) in heart failure patients. Univariant analysis showed that NT-proANP and NT-proBNP were positively correlated to LAD, LVEDD and negatively correlated to LVEF (all P<0.05) while there was no significant correlation between NT-proCNP and echocardiographic derived parameters of cardiac function in heart failure patients. Multivariate stepwise regression analysis including age, gender, NYHA classification, LAD, LVEDD and LVEF revealed that NYHA classification, LVEF, LAD and age were independent predictors of NT-proANP; while NYHA classification, LVEF and age were independent predictors of NT-proBNP while there was no association among these factors and NT-proCNP.</p><p><b>CONCLUSION</b>In heart failure patients, the plasma concentration of NT-proANP, NT-proBNP and NT-proCNP were significantly increased and NT-proANP, NT-proBNP but not NT-proCNP were significantly correlated to NYHA classification and echocardiographic derived parameters of cardiac function.</p>

Association of serum uric acid, plasma NT-proBNP, Hs-C reactive protein and invasive hemodynamic parameters in patients with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the correlation of serum uric acid, invasive hemodynamic parameters, plasma N-terminal proBNP (NT-proBNP) and Hs-C reactive protein (Hs-CRP) in patients with heart failure.</p><p><b>METHOD</b>Invasive hemodynamic parameters derived from Swan-Ganz catheter, serum uric acid, plasma NT-proBNP and Hs-CRP within 12 hours after hospital admission were analyzed in 141 patients with chronic heart failure [New York Heart Association (NYHA) class II-IV].</p><p><b>RESULTS</b>Incidence of hyperuricemia was 55.30% in this patient cohort. Pulmonary capillary wedge pressure (PCWP) and plasma NT-proBNP in hyperuricemia patients were significantly higher than those in non-hyperuricemia patients (P < 0.01). The percentages of high plasma NT-proBNP (> 600 pmol/L) and hyperuricemia were significantly higher in patients with PCWP > or = 18 and < 28 mm Hg (1 mm Hg = 0.133 kPa) and patients with PCWP > or = 28 mm Hg compared those in patients with PCWP < 18 mm Hg, (P = 0.01, P = 0.02; P < 0.01, P < 0.01, respectively). Partial correlation analysis showed that serum uric acid correlated with right atrial pressure, right ventricular pressure, pulmonary arterial pressure and PCWP (r = 0.19, P = 0.03; r = 0.45, P < 0.01; r = 0.23, P = 0.01; r = 0.24, P = 0.01, respectively). Multiple linear regression analysis showed both serum uric acid and plasma NT-proBNP correlated independently with PCWP (beta = 0.24, P = 0.01; beta = 0.47, P < 0.01, respectively) while plasma Hs-CRP and left ventricular ejection fraction were not correlated with serum uric acid and PCWP (P > 0.05).</p><p><b>CONCLUSION</b>Serum uric acid independently correlated with PCWP in patients with heart failure and the combined measurements of serum uric acid and plasma NT-proBNP are helpful in evaluating the prognosis of patients with heart failure.</p>