Association between left ventricular reverse remodeling and long-term outcomes after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

There is a paucity of data regarding the effect of left ventricular (LV) reverse remodeling (r-LVR) on diastolic function and outcomes after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study was to identify the impact of r-LVR on the outcome and the predictors of such changes after ASA. Eighty-seven patients (57.5% men) were enrolled and underwent both echocardiography and cardiovascular magnetic resonance (CMR) imaging at baseline and 27 months after the procedure. The study population was divided into two groups by the degree of r-LVR. Compared to the greater r-LVR group, the lesser r-LVR group had a significantly larger LV mass (LVM) and lower diastolic function parameters at baseline. The greater r-LVR group had significantly greater LVM regression and improvement of diastolic function after ASA. Kaplan‒Meier analysis showed significantly worse composite events in the lesser r-LVR group after ASA (P = 0.016). After adjusting for multiple clinical variables, r-LVR was associated with an improved E/e' (ß = 0.390, p < 0.001) and reduced events (hazard ratio: 0.795; 95% confidence interval (CI), 0.644-0.983; p = 0.034). Preablation LVM was associated with a decreased probability of r-LVR (ß = -0.228, p = 0.021) and diastolic function improvement (ß= -0.245, p = 0.006). r-LVR was associated with long-term outcome benefit in patients with HOCM. Preablation LVM prevented LV from favoring reverse remodeling and thus may be a potential parameter for risk stratification and prognosis after ASA treatment.

Preoperative myocardial fibrosis is associated with worse survival after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: A delayed enhanced cardiac magnetic resonance study.

Background: Prior studies have shown that myocardial fibrosis can be detected by late gadolinium enhancement (LGE) of cardiac magnetic resonance (CMR) and might be associated with higher mortality risk in hypertrophic cardiomyopathy (HCM). The objective of this study was to examine the prognostic utility of CMR in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). Materials and methods: We conducted a retrospective study which consisted of 183 consecutive patients with symptomatic drug-refractory HOCM who underwent CMR for assessment of myocardial fibrosis before ASA. The cardiovascular disease related survival was evaluated according to LGE-CMR status. Results: The cohort comprised 74 (40.4%) women with a mean age of 51 ± 8 years. Preoperative myocardial fibrosis was detected in 148 (80.9%) patients. After a median of 6 years (range 2-11 years) follow-up, adverse clinical events occurred in 14 (7.7%) patients. Multivariate-adjusted Cox regression analyses revealed that age [hazard ratio (HR) 1.142 (1.059-1.230), p = 0.001] and LGE [HR 1.170 (1.074-1.275), p < 0.001] were independent predictors of cardiovascular mortality during follow-up. Conclusion: Preoperative myocardial fibrosis measured by LGE-CMR was an independent predictor of increased adverse clinical outcomes in patients with HOCM undergoing ASA and could be used for the pre-operative evaluation of risk stratification and long-term prognosis after ASA in these patients.

Sex-related differences in left ventricular remodeling and outcome after alcohol septal ablation in hypertrophic obstructive cardiomyopathy: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Alcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA. METHODS: A total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured. RESULTS: Women had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan-Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes. CONCLUSIONS: Males with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.

Association of Perioperative Myocardial Injury with 30-Day and Long-Term Mortality in Older Adult Patients Undergoing Orthopedic Surgery in China.

BACKGROUND Myocardial injury after noncardiac surgery (MINS) is common and associated with postoperative mortality. We assessed MINS occurrence and association with 30-day and long-term mortality in older adult patients undergoing orthopedic surgery in China. MATERIAL AND METHODS This was a retrospective study of consecutive patients who underwent orthopedic surgery between January 1, 2009, and December 31, 2017, at Beijing Jishuitan Hospital. MINS was defined as postoperative troponin I peak elevation above the 99th percentile upper reference limit (>0.034 µg/L) within 30 days after surgery. Outcomes were 30-day postoperative mortality and long-term all-cause mortality. RESULTS From 34 901 patients, 5897 (16.9%) had serial troponin I measurements, and 266 (4.5%) had MINS after surgery. Mean patient age was 71.1±9.2 years; 32.9% were male. Among patients with MINS, 180 had myocardial infarction (MI) (3.2%). Patients with MI had higher 30-day and long-term mortality than those without MI (8.9% vs 1.2%; P<0.016 and 18.9% vs 3.5%; P=0.001). Male sex (OR 5.87, 95% CI 1.75-19.67; P=0.004), RCRI ≥2 (OR 5.05, 95% CI 1.67-15.31; P=0.004), and MI (OR 9.13, 95% CI 1.13-73.63; P=0.011) were independently associated with 30-day mortality. Age (HR 1.07, 95% CI 1.03-1.11; P=0.001), male sex (HR 2.96, 95% CI 1.51-5.80; P=0.002), RCRI ≥2 (HR 2.01, 95% CI 1.03-3.94; P=0.041), orthopedic trauma (HR 3.40, 95% CI 1.00-11.44; P=0.049), and MI (HR 7.33, 95% CI 2.22-24.20; P=0.001) were predictors of 2-year mortality. CONCLUSIONS Perioperative MI was independently associated with 30-day and long-term mortality after orthopedic surgery, providing a potential indicator of high risk of mortality in patients who could benefit from targeted prevention and intervention.

Characteristics and long-term mortality of patients with ST-elevation or non-ST-elevation myocardial infarction after orthopaedic surgery.

OBJECTIVE: To investigate the clinical characteristics and long-term mortality of patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) after orthopaedic surgery. METHODS: This retrospective, single-centre study enrolled patients that underwent inpatient orthopaedic surgery from 2009 to 2017 in Beijing Jishuitan Hospital. The patients were screened for a cardiac troponin I elevation and fulfilled the Fourth Universal Definition of Myocardial Infarction within 30 days of surgery. RESULTS: A total of 180 patients that developed perioperative myocardial infarction (MI) were included in the study. Among them, 14 patients (7.8%) were classified as STEMI, and 166 (92.2%) had NSTEMI. Compared with those with NSTEMI, STEMI patients had significantly higher 30-day and long-term mortality rates (50.0% versus 5.4%; 71.4% versus 22.3%; respectively). Multivariate Cox regression model analysis among the entire cohort demonstrated that STEMI (hazard ratio [HR] 5.78, 95% confidence interval [CI] 2.50, 13.38) and prior MI (HR 2.35, 95% CI 1.02, 5.38) were the most significant independent predictors of long-term mortality. CONCLUSION: Perioperative MI after orthopaedic surgery was associated with a high mortality rate. STEMI was independently associated with a significant increase in short- and long-term mortality.

Clinical characterization and outcome of prolonged heart rate-corrected QT interval among children with syndactyly.

Prolonged heart rate-corrected QT (QTc) interval is an independent risk factor for sudden cardiac death, which is the hallmark of Timothy syndrome (TS). There are little data on children with syndactyly and QTc prolongation.To evaluate the characteristics and long-term outcomes in children with syndactyly, and to attempt to identify TS in patients with syndactyly and QTc prolongation.This is a retrospective case-control study of children with syndactyly who visited Beijing Jishuitan Hospital between July 2003 and February 2013. The patients with prolonged QTc intervals are matched 1:4 with patients without prolongation. Genetic testing of the CACNA1C gene is routinely performed in patients with QTc prolongation.The mean age at admission is 3.4 ±â€Š2.3 years. Compared with the normal QTc group, those with QTc prolongation showed higher frequencies of congenital heart disease (11.8% vs 1.5%, P = .042), mental retardation and facial dysmorphia (11.8% vs 0, P = .004), and T wave alternans (23.5% vs 4.4%, P = .01). In the multivariable analysis, only T wave alternans (OR = 10.61, 95%CI: 1.39-81.16, P = .023) is independently associated with QTc prolongation in patients with syndactyly. One child with QTc prolongation had a mutation in the CACNA1C gene. No patients with prolonged QTs interval met the threshold for TS.Children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities. T wave alternans is independently associated with QTc prolongation in patients with syndactyly.

Sex differences in the association of abdominal adipose tissue and anthropometric data with untreated hypertension in a Chinese population.

BACKGROUND: There are inconsistent interpretations of the interrelationship of adiposity, anthropometric indices, and blood pressure (BP) in hypertensive patients. Additionally, whether these relationships differ between sexes is unknown. We aimed to elucidate the associations of adiposity indices measured using quantitative computed tomography (QCT) with BP and hypertension and to determine the effect of sex on the interrelationship of these parameters in a Chinese population. METHODS: Abdominal adipose fat, including the visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, was measured by QCT in 1488 patients (514 men, 974 women). Body mass index (BMI), waist circumference (WC), hip circumference (HC), and systolic (SBP) and diastolic BP (DBP) were measured. Pearson correlation coefficients, multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the relationship and potential of adiposity indices to BP and risk of hypertension within sex groups. RESULTS: Men had significantly greater VAT area but less SAT area than women in hypertensive group. VAT, SAT, and WC were more highly correlated with SBP in men than in women. After controlling for body weight, height, and age, VAT area and WC were positively associated with SBP (VAT: ß = 0.309, p < 0.001; WC: ß = 0.148, p = 0.001) and DBP (VAT: ß = 0.099, p = 0.034; WC: ß = 0.198, p = 0.001) in women. VAT area was positively associated with SBP (ß = 0.444, p < 0.001) and DBP (ß = 0.146, p = 0.021) in men. WC had a significant correlation with an increased risk of hypertension in women but a borderline association in men (p = 0.059) when adjusted for VAT area and SAT area. CONCLUSIONS: The association of abdominal adiposity with hypertension differs qualitatively by sex. WC may be an important determinant of hypertension and may be used for risk stratification for hypertension among Chinese individuals.

Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM. METHODS: Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis. RESULTS: LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs. 866.6 [707.2-1875.2] pmol/L, P = 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025 ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%. CONCLUSIONS: Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.

Effects of alcohol septal ablation on left ventricular diastolic filling patterns in obstructive hypertrophic cardiomyopathy.

Alcohol septal ablation (ASA) has been shown to improve left ventricular (LV) diastolic function in patients with obstructive hypertrophic cardiomyopathy (HCM). However, its beneficial effect on diastolic function assessed by cardiac magnetic resonance (CMR) has not been reported. We investigated the mid-term changes of diastolic function by CMR combined with echocardiography in HCM patients after ASA at a median of 14-month follow-up. CMR parameters of diastolic function including peak filling rate (PFR), and time to peak filling rate (TPFR) were evaluated in 43 patients (aged 48 ± 9 years). LV diastolic function improved significantly measured by echocardiography with the decrease in ratio of transmitral early LV filling velocity (E) to early diastolic mitral lateral annular velocity (E') (14.20 ± 1.17 to 11.58 ± 1.16, p < 0.001) and E-wave deceleration time (194.04 ± 19.30 to 168.45 ± 12.58 ms, p < 0.001). PFR increased significantly with associated decrease in TPFR after ASA (both p < 0.001) at follow-up. Furthermore, patients with larger decrease in LVOT gradients had a greater improvement of LV diastolic function, as measured by the reduction of E/E' (p < 0.001) and increase of PFR (p < 0.001). In conclusion, this study demonstrated that successful ASA results in both echocardiographic and CMR indices of diastolic function improvement after ASA at 14-month follow-up. ASA therapy can significantly reduce LVOT gradient and mitral regurgitation, both of which may contribute to the improvement of diastolic function.

Left ventricular remodeling and fibrosis: Sex differences and relationship with diastolic function in hypertrophic cardiomyopathy.

OBJECTIVES: We investigated sex differences in left ventricular (LV) remodeling and fibrosis and their relationship with LV diastolic dysfunction by cardiovascular magnetic resonance (CMR). METHODS: CMR imaging was performed simultaneously in 152 age-matched patients (76 men, 76 women; mean age: 49±9 years) without LV systolic dysfunction. LV remodeling index (LVRI) was calculated as the ratio of LV mass and end-diastolic volume. Diastolic function indexes including peak filling rate (PFR) and time to PFR (tPFR) were evaluated. Extent of late gadolinium enhancement (LGE) was measured. RESULTS: LVRI and extent of LGE were greater in women compared with men (1.48±0.22 vs. 1.36±0.28g/ml; 13.15±2.48 vs. 11.35±2.34g, respectively, both P<0.001). Women had lower PFR and higher tPFR (both P<0.001) than men. LVRI and the extent of LGE showed significant relationships with parameters of diastolic function in both sex. In a multivariate analysis, LVRI remained a strong independent predictor of PFR and TPFR in women (ß=-0.272, P=0.032; ß=0.348, P=0.016, respectively), and in men (ß=-0.374, P<0.001; ß=0.660, P<0.001, respectively). Furthermore, the extent of LGE also remained an independent predictor of PFR in women (ß=-0.283, P=0.033) and men (ß=-0.492, P<0.001). CONCLUSIONS: There are prominent sex differences in LV remodeling and myocardial fibrosis. We suggest that the effects of LV remodeling and fibrosis may lead to diastolic dysfunction with greater susceptibility to worse clinical outcome in women.

Biventricular reverse remodeling after successful alcohol septal ablation for obstructive hypertrophic cardiomyopathy.

The aim of the present study was to investigate the long-term effects of alcohol septal ablation (ASA) on left ventricular (LV) and right ventricular (RV) remodeling in patients with obstructive hypertrophic cardiomyopathy (HC) using cardiovascular magnetic resonance (CMR). CMR was performed at baseline and 16 months after ASA in 38 patients with obstructive HC (mean age 48 ± 9 years) despite optimal medical treatment. ASA resulted in significant reductions of LV outflow tract gradient (mean 89 ± 22 vs 24 ± 12 mm Hg, p <0.001) and improvements in New York Heart Association functional class (p <0.001) during the follow-up period. LV remote mass and septal mass decreased from 98.34 ± 37.02 to 84.23 ± 34.71 g and from 77.56 ± 16.40 to 68.43 ± 14.02 g, respectively (p <0.001 for both) at 16-month follow-up. There were significant reductions of RV mass (mean 53.69 ± 7.12 vs 47.49 ± 6.17 g, p <0.001) and improvements in RV end-diastolic volume (mean 110.58 ± 22.47 vs 124.22 ± 24.17 ml, p <0.001) and the RV ejection fraction (p <0.001) during 16-month follow-up. Linear regression analysis showed that LV outflow tract gradient reduction was correlated significantly with LV remote mass reduction (r = 0.475, p = 0.003) and RV mass reduction (r = 0.535, p = 0.001) at 16-month follow-up. In conclusion, successful ASA can lead to positive biventricular reverse remodeling, showing significant reductions of RV and LV mass as well as increased RV and LV end-diastolic volumes during follow-up.

17ß-estradiol prevents cardiac diastolic dysfunction by stimulating mitochondrial function: a preclinical study in a mouse model of a human hypertrophic cardiomyopathy mutation.

OBJECTIVE: We investigated the effect of ovariectomy (OVX) and 17ß-estradiol (E2) replacement on both mitochondrial and myocardial function in cTnT-Q92 transgenic mice generated by cardiac-restricted expression of a human hypertrophic cardiomyopathy (HCM) mutation. METHODS: The cTnT-Q92 mice were ovariectomized at twenty weeks of age and were treated with either placebo (OVX group) or E2 (OVX+E2 group) for twelve weeks before being sacrificed. Wild-type and cTnT-Q92 female mice receiving sham operation were used as controls. Indices of diastolic function such as mitral early (E) and late (A) inflow as well as isovolumic relaxation time (IVRT) were measured by echocardiography. A Clark-type electrode was used to detect respiratory control, and ATP levels were determined at the mitochondrial level using HPLC. Key components related to mitochondrial energy metabolism, such as peroxisome proliferator-activated receptor α (PPARα), PPARγ coactivator 1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1), were also analyzed using Western blot and RT-PCR. The levels of oxidative stress markers were determined by measuring malondialdehyde (MDA) using the thiobarbituric acid assay. RESULTS: The cTnT-Q92 mice had impaired diastolic function compared with wild-type mice (E/A ratio, 1.39 ± 0.04 vs. 1.21 ± 0.01, p<0.001; IVRT, 19.17 ± 0.85 vs. 22.15 ± 1.43 ms, p=0.028). In response to ovariectomy, cardiac function further decreased compared with that observed in cTnT-Q92 mice that received the sham operation (E/A ratio, 1.15 ± 0.04 vs. 1.21 ± 0.01, p<0.001; IVRT, 28.31 ± 0.39 vs. 22.15 ± 1.43 ms, p=0.002). Myocardial energy metabolism, as determined by ATP levels (3.49 ± 0.31 vs. 5.07 ± 0.47 µmol/g, p<0.001), and the mitochondrial respiratory ratio (2.04 ± 0.10 vs. 2.63 ± 0.11, p=0.01) also decreased significantly. By contrast, myocardial concentrations of MDA increased significantly in the OVX group, and PGC-1α, PPARα and NRF-1decreased significantly. E2 supplementation significantly elevated myocardial ATP levels (4.55 ± 0.21 vs. 3.49 ± 0.31 µmol/g, p=0.003) and mitochondrial respiratory function (3.93 ± 0.05 vs. 2.63 ± 0.11, p=0.001); however, it reduced the MDA level (0.21 ± 0.02 vs. 0.36 ± 0.03 nmol/g, p<0.001), which subsequently improved diastolic function (E/A ratio, 1.35 ± 0.06 vs. 1.15 ± 0.04, p<0.001; IVRT, 18.22 ± 1.16 vs. 28.31 ± 0.39 ms, p=0.007). CONCLUSIONS: Our study has shown that 17ß-estradiol improved myocardial diastolic function, prevented myocardial energy dysregulation, and reduced myocardial oxidative stress in cTnT-Q92 mice.