The triglyceride-glucose index as a potential protective factor for hypertrophic obstructive cardiomyopathy without diabetes: evidence from a two-center study.

OBJECTIVE: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes. RESEARCH DESIGN AND METHODS: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients. RESULTS: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients. CONCLUSIONS: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis.

Association Between Thyroid Dysfunction and Incidence of Atrial Fibrillation in Patients With Hypertrophic Obstructive Cardiomyopathy.

Objective: To explore the correlation between the incidence of atrial fibrillation (AF) and thyroid dysfunction in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Thyroid function testing in 755 consecutive patients with HOCM were examined at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013. Patients were divided into four groups according to the TSH levels: TSH<0.55 mIU/L(n=37)、0.55~2.49 mIU/L (n=490)、2.50~9.9 mIU/L (n=211) and >10.00mIU/L(n=17). Results: A total of 107 patients were diagnosed with AF (14%).(1) Compared to HOCM patients without AF,HOCM patients with AF have older age (P<0.001), higher NT-proBNP (P=0.002), higher Cr (P=0.005), larger left atrial diameter(P=0.001), lower FT3 (P=0.046), higher FT4 (P=0.004).(2) In the four groups according to the TSH levels: TSH<0.55 mIU/L, 0.55~2.49mIU/L, 2.50~9.9mIU/L and ≥10.00mIU/L, the incidence of AF was 27.02%(10/37),10.20%(50/490), 19.43%(41/211), and 35.29%(6/17), respectively. Both high and low TSH levels were associated with an increased incidence of AF. After adjusting for the common risk factor (age, NT-proBNP, and so on), stepwise multiple logistic regression analysis revealed that TSH levels were significantly related to AF incidence.Compared to patients with TSH 0.55~2.49 mlU/L, the adjusted odds ratio of AF for TSH<0.55, 2.50~9.99, ≥10.00 mIU/L were 1.481 (95% CI 0.485~4.518,P=0.490), 1.977 (95%CI 1.115~3.506, p=0.02), 4.301 (95%CI 1.059~17.476, P=0.041), respectively. Conclusion: Our results suggested that thyroid dysfunction was associated with an increased risk of AF in patients with HOCM.

The Association Between High-Sensitivity C-Reactive Protein/Albumin Ratio and Cardiovascular Prognosis in Patients Undergoing Percutaneous Coronary Intervention.

Limited studies have focused on the impact of high-sensitivity C-reactive protein (hsCRP) to albumin ratio (CAR) on cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Hence, the present study evaluates the association between CAR and cardiovascular outcomes in patients undergoing drug-eluting stent (DES) implantation. We consecutively enrolled 9375 CHD patients undergoing DES implantation. All patients were divided into 3 groups according to their CAR: tertile 1 (CAR ≤.02, n=3125), tertile 2 (.02.06, n = 3125). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Kaplan-Meier analysis indicated that the incidences of MACCE and MI increased with high tertiles of the CAR (MACCE: 8.7 vs 10.5 vs 12.3%, log-rank P < .001; MI: 3.3 vs 4.0 vs 4.7%, long-rank P = .015). Cox regression analysis suggested that CAR was an independent risk factors for MACCE (HR per standard deviation (SD) increase: 1.07, 95% CI, 1.01-1.14, P = .024), and MI (HR per SD increase: 1.11, 95% CI, 1.01-1.22, P = .028). In conclusion, the CAR is an independent predictor of MACCE and MI in CHD patients.

Hypertrophic Obstructive Cardiomyopathy: Comparison of Outcomes After Myectomy or Alcohol Ablation.

Introduction and Objectives: The risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy. Methods: The original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation. Results: Both in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the <56 years group. Conclusions: The patients with medical treatments seemed to suffer from the highest risk of achieving an all-cause mortality and the endpoint of heart transplantation. In the long-term survival and clinical outcome, myectomy seemed better than alcohol septal ablation, especially the younger patients. Due to the less-controllable degree, periprocedural complication frequency after alcohol septal ablation was higher, compared with myectomy. Furthermore, gradients after myectomy are lower at late follow-up. To sum up, when selecting treatment strategies, the patients should be individually evaluated by a multidisciplinary team of cardiologists and surgeons.

Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study.

BACKGROUND: Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS: The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS: Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04-0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18-0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42-0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49-0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27-0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68-0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32-0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81-0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS: Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study.

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (ß = 0.052, P = 0.002) and LDL (ß = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (ß = 0.240, P = 0.033) and LDL (ß = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION: Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Uric acid is associated with cardiac death in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: The role of uric acid (UA) in survival of patients with hypertrophic obstructive cardiomyopathy (HOCM) has not been fully evaluated. This study aimed to determine whether UA could be an independent risk factor of cardiac death in patients with HOCM. METHODS: A total of 317 patients with HOCM, who were receiving conservative treatment in Fuwai Hospital from October 2009 to December 2014, all of them completed UA evaluations, were analyzed. Patients were divided into three groups according to the UA levels: Tertile 1 (≤ 318 µmol/L, n = 106), Tertile 2 (319 to 397 µmol/L, n = 105), and Tertile 3 (≥ 398 µmol/L, n = 106). RESULTS: During a median follow-up of 45 months, 29 cardiac deaths (9.1%) occurred, including 6 sudden cardiac deaths and 23 heart failure-related deaths. Cardiac death in Tertile 3 (n = 16, 55.2%) was significantly higher than in Tertile 1 (n = 6, 20.7%) and Tertile 2 (n = 7, 24.1%). In univariate model, UA level (continuous value) showed predictive value of cardiac death [hazard ratio (HR) = 1.006, 95% CI: 1.003-1.009,P = 0.009]. Univariate Cox survival analysis had shown a significant higher property of cardiac death in patients of Tertile 3 when compared with those of Tertile 1, but cardiac death in patients of Tertile 2 did not show significant prognositic value compared with those of Tertile 1 (HR = 3.927, 95% CI: 0.666-23.162,P = 0.131). UA was found to be an independent risk factor (HR = 1.005, 95% CI: 1.001-1.009,P = 0.009) of cardiac death in the multivariate regression analysis after the adjustment for age, body mass index, atrial fibrillation, hemoglobin, creatinine, high-sensitivity C-reactive protein, interventricular septum/left ventricular posterior wall ratio, left ventricular outflow tract and left ventricular ejection fraction. CONCLUSIONS: UA concentration was found to be independently associated with cardiac death in HOCM patients receiving conservative treatment. Randomized trials of UA-lowering agents for HOCM patients are warranted.

Efficacy and safety of levothyroxine (L-T4) replacement on the exercise capability in chronic systolic heart failure patients with subclinical hypothyroidism: Study protocol for a multi-center, open label, randomized, parallel group trial (ThyroHeart-CHF).

BACKGROUND: Subclinical hypothyroidism is a common condition in patients with heart failure and is defined as elevated serum thyroid hormone (TSH) with normal circulating free thyroxine (FT4). Evidence on the effect of thyroid hormone treatment is lacking. We designed a randomized controlled trial to compare the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. METHODS/DESIGN: Eligible participants were identified from the cardiology units of five study centers based on the following criteria: 18 years or older, systolic heart failure with NewYork Heart Association (NYHA) class II-III, left ventricular ejection fraction ≤ 40%, and subclinical hypothyroidism (TSH > 4.78µIU/ml, < 10 µIU/ml + FT4 level within reference range). Eligible patients will be randomly assigned in a 1:1 manner to receive thyroxine replacement therapy plus standard chronic heart failure (CHF) treatment or only standard CHF therapy. Levothyroxine will be administered at an initial dose of 12.5 µg once daily and will be titrated until TSH is within the normal range. The primary endpoints include the difference in distance of the six-minute walk test between 24 weeks and baseline. The secondary endpoints include differences in plasma NT-proBNP levels and serum lipid profiles, changes in the NYHA classification, cardiovascular death, re-hospitalization, differences in echocardiographic and cardiac magnetic resonance imaging measures, and Minnesota Living With Heart Failure Questionnaire (MLHFQ) results between 24 weeks and baseline. DISCUSSION: ThyroHeart-CHF is designed as a prospective, multi-center, randomized, controlled clinical trial to study the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. The study findings will have significant implications for discovering the new therapeutic targets and methods of heart failure. TRAIL REGISTRATION: ClinicalTrials.gov, NCT03096613 . Registered on 30 March 2017.