Arrhythmogenic right ventricular cardiomyopathy with sustained ventricular tachycardia: a case report.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. CASE PRESENTATION: A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. CONCLUSION: Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

Airflow obstruction, impaired lung function and risk of sudden cardiac death: a prospective cohort study.

BACKGROUND: Growing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD). OBJECTIVES: We aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities. METHODS: A total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987-1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth's penalised partial likelihood correction were used to estimate the HRs. RESULTS: Over a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV1 in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV1 were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV1 significantly improved the predictive power for SCD. CONCLUSIONS: Impaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.

Diagnosis of left anterior descending branch-right ventricular fistula with giant coronary artery aneurysm by contrast echocardiography: A case report.

BACKGROUND: Coronary fistulae are communications between a coronary artery and a heart chamber or vessel. The final diagnosis is usually made by coronary angiography or computed tomographic (CT) angiography. Here we report a case by employing contrast echocardiography in diagnosis of a giant coronary aneurysm with right ventricle (RV) fistula. CASE PRESENTATION: The patient, a 29-year-old woman, referred to our institution with a complaint of palpitation occasionally. Transthoracic echocardiogram showed a spherical, echogenic structure in the apex of RV. Proximal to the aneurysm, the left anterior descending branch (LAD) remained enlarged (8-9 mm) and showed a fistulous communication with the echogenic structure. A contrast echocardiography was performed, and 4-5 cardiac cycle after the left ventricle was enhanced, the echogenic structure started to become more prominent and several fistulae were seen between RV and the echogenic structure. Computed tomography (CT) angiography and coronary angiography confirmed the dilation (9 mm in diameter) of the LAD with an aneurysm at the distal segment of the LAD, with a small amount of iodinated contrast agent flowing into the subsequent region of the RV, thereby characterizing a LAD-to-RV fistula. CONCLUSION: The final diagnosis of fistula is usually made by coronary angiography or CT angiography. However, contrast echocardiography is also a well-established method for the demonstration of intracardiac shunting. In this case, the contrast echocardiography clearly revealed one of the fistulae between the aneurysm and RV.

A novel DPP6 variant in Chinese families causes early repolarization syndrome.

Previous studies demonstrated that variants in dipeptidyl aminopeptidase-like protein-6 (DPP6) are involved in idiopathic ventricular fibrillation. However, its role in early repolarization syndrome (ERS) remains largely elusive. The aim of this study is to determine whether the novel DPP6-L747P variant is associated with ERS, and explore the underlying mechanisms. In our study, whole genome sequencing was used to identify a genetic variant in 4 Chinese families with sudden cardiac arrest induced by ERS. Then, wild-type (WT) DPP6 or mutant (c.2240T > C/p.L747P) DPP6 were respectively expressed in HEK293 cells, co-expressed with KV4.3 and KChIP2. Western blotting, immunofluorescence, and whole-cell patch clamp experiments were performed to reveal possible underlying mechanisms. A novel missense variant (c.2240T > C/p.L747P) in DPP6 was identified in the 4 families. Both DPP6-WT and DPP6-L747P were mainly located on the cell membrane. Compared with DPP6-WT, the intensity of DPP6 protein bands was downregulated in DPP6-L747P. Functional experiments showed that macroscopic currents exhibited an increase in DPP6-L747P, and the current intensity of DPP6-L747P was increased more than that of DPP6-WT (63.1 ± 8.2 pA/pF vs.86.5 ± 15.1 pA/pF at +50 mV, P < 0.05). Compared with DPP6-WT, the slope of the activation curve of DPP6-L747P was slightly decreased (15.49 ±â€¯0.56 mV vs. 13.88 ±â€¯0.54 mV, P < 0.05), the slope of the inactivation curve was increased (13.65 ±â€¯1.57 mV, vs. 24.44 ±â€¯2.79 mV, P < 0.05) and the recovery time constant was significantly reduced (216.81 ±â€¯18.59 ms vs. 102.11 ±â€¯32.03 ms, P < 0.05). In conclusion, we identified a novel missense variant (c.2240T > C/p. L747P) in DPP6 in 4 Chinese families with sudden cardiac arrest induced by ERS. Patch clamp experiments revealed that this variant could generate a gain of function of Ito and affect the potassium current. These results demonstrated that changes caused by the variant may be the underlying mechanisms of malignant arrhythmias in the individuals with ERS.

Early repolarization pattern associated with coronary artery disease and increased the risk of cardiac death in acute myocardium infarction.

BACKGROUND: Early repolarization pattern (ERP) was associated with sudden cardiac death in recent studies. However, the associations between ERP and coronary artery disease (CAD), and ERP and cardiac death caused by acute myocardial infarction (MI) remains unclear. METHODS: We retrospectively enrolled consecutive 1,545 CAD patients and 908 non-CAD subjects as control group which were confirmed by coronary angiograph. The CAD patients include stable CAD, acute MI patients, and old MI patients. Multivariate logistic regression was employed to evaluate the relationship between ERP and CAD, and ERP and cardiac death caused by acute MI. RESULTS: Of the 1,545 CAD subjects, there were 1,029 stable CAD patients, 404 acute MI patients, and 112 old MI patients. The incidence of ERP was much higher among patients with CAD than without CAD subjects (20.1% vs. 6.2%, p < .001) after adjusting for major cardiovascular risk factors. No significant correlation was observed between lead region of ERP on 12-lead ECG and single abnormal artery. Of the 404 acute MI patients, 342 patients survived and 62 patients died. Incidence of ERP was higher in non-survivor than survivor patients with acute MI (24.2% vs. 17.5%, p = .006) after adjustment for major cardiovascular risk factors. CONCLUSION: The incidence of ERP was higher in CAD patients than subjects without CAD and in non-survivor patients than survivor patients with acute MI. The lead region of ERP on 12-lead ECG was not associated with single abnormal coronary artery.

Myocardial contrast echocardiography in the diagnosis of postoperative takotsubo myocardiopathy: case report and literature review.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is a brief ventricular dysfunction that usually occurs after emotional or physical stress. Here, we report a patient who underwent cardiac surgery and then developed TCM during the postoperative period. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital complaining of chest tightness, palpitations and dyspnoea after activity. An echocardiogram performed by our hospital showed rheumatic heart disease (severe mitral stenosis and regurgitation) with normal cardiac function and wall motion. After mitral valve replacement, this patient developed heart failure with low blood pressure and tachycardia. Urgent bedside echocardiography demonstrated akinesis in the middle and apical segments of the left ventricle and a depressed ejection fraction (EF) of 36%. Myocardial contrast echocardiography (MCE) showed similar enhancement intensity in the basal, middle and apical segments. Quantitative analysis showed approximately equivalent maximum intensity in these regions. The diagnosis was considered TCM instead of myocardial infarction. Then, an intra-aortic balloon pump was inserted to maintain effective circulation and reduce the postcardiac load. Given ventilation therapy, postoperative anticoagulation therapy and anti-infection treatment, the patient recovered quickly. In the follow-up examination, the patient remained asymptomatic and showed normalization of ventricular wall motion in the apical segment. CONCLUSION: This report presents a case of TCM in which MCE was used to demonstrate intact microvascular perfusion despite apical akinesis. This report might support the use of MCE as a substitute for invasive coronary angiography.

Weaker masturbatory erection may be a sign of early cardiovascular risk associated with erectile dysfunction in young men without sexual intercourse.

INTRODUCTION: Although increasing evidences emphasize the importance of early cardiovascular evaluation in men with erectile dysfunction (ED) of unexplained aetiology, impaired masturbation-induced erections in young men are usually overlooked and habitually presumed to be psychological origin. AIMS: To evaluate the young men presenting weaker masturbatory erection with no sexual intercourse (WME-NS) and verify if this cohort have early cardiovascular risks associated with ED. METHODS: Male subjects aged 18-40 years with WME-NS were screened by analyzing detailed sexual intercourse and masturbatory history. The age-matched ED and non-ED population were identified by using International Index of Erectile Function-5 (IIEF-5). All subjects with acute and/or chronic diseases (including diagnosed hypertension and diabetes) and long-term pharmacotherapy were excluded. Nocturnal penile tumescence and rigidity (NPTR), systemic vascular parameters and biochemical indicators related to metabolism were assessed. MAIN OUTCOME MEASURES: Comparison analysis and logistic regression analysis were conducted among WME-NS, ED and non-ED population. RESULTS: In total, 78 WME-NS cases (mean 28.99 ± 5.92 years), 179 ED cases (mean 30.69 ± 5.21 years) and 43 non-ED cases (mean 28.65 ± 4.30 years) were screened for analysis. Compared with non-ED group, WME-NS group had higher prevalence of early ED risk factors including endothelial dysfunction, insulin resistance, high level of glycosylated serum protein and abnormal NPTR. Multivariable-adjusted logistic regression analysis showed endothelia dysfunction (odds ratio: 8.83 vs. 17.11, both P < 0.001) was the independent risk factor for both WME-NS and ED. CONCLUSIONS: Weaker masturbatory erection may be a sign of early cardiovascular risk associated with ED in young men without sexual intercourse. More studies are warranted to elucidate the clinical benefits by targeting these formulated strategies.

Effects of Nardostachys chinensis on spontaneous ventricular arrhythmias in rats with acute myocardial infarction.

OBJECTIVES: To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI). METHODS: Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR. RESULTS: Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P < 0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P < 0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone. CONCLUSIONS: NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.

Current and former smoking and risk for venous thromboembolism: a systematic review and meta-analysis.

BACKGROUND: Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose-response relationship exists. METHODS AND FINDINGS: We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09-1.25) for ever smokers, 1.23 (95% CI 1.14-1.33) for current smokers, and 1.10 (95% CI 1.03-1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%-11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%-8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24-1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%-12.3%) for ever smoking, 5.8% (95% CI 3.6%-8.2%) for current smoking, and 2.7% (95% CI 0.8%-4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4-26.7) cases per 100,000 person-years. CONCLUSIONS: Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE. Please see later in the article for the Editors' Summary.

Simvastatin reduces myocardial injury undergoing noncoronary artery cardiac surgery: a randomized controlled trial.

OBJECTIVE: Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality. We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms. METHODS AND RESULTS: One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were randomly assigned to either a statin group (n=77) or a control group (n=74). Simvastatin (20 mg) was administered preoperatively and postoperatively. Plasma were analyzed for troponin T, isoenzyme of creatine kinase, C-reaction protein, interleukin-6, interleukin-8, creatinine, and blood urea nitrogen. Cardiac echocardiography was performed. Endothelial nitric oxide synthase (eNOS), Akt, p38, heat shock protein 90, caveolin-1, and nitric oxide (NO) in the heart were detected. Simvastatin significantly reduced plasma troponin T, isoenzyme of creatine kinase, C-reaction protein, blood urea nitrogen , creatinine, interleukin-6, interleukin-8, and the requirement of inotropic postoperatively. Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin also improved cardiac function postoperatively. CONCLUSIONS: Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01178710.

Administration of macrolide antibiotics increases cardiovascular risk.

Background: The increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades. Methods: Medline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model. Results: A total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use. Conclusion: Administration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.

Inflammatory pseudotumor of the right ventricle in a 35-year-old woman with Behçet's disease: a case report.

Inflammatory pseudotumor is a rare benign neoplasm. It is common in children and has been reported in various locations throughout the body but rarely in the heart. Behçet's disease is a multisystemic, recurrent, inflammatory disorder. We report a 35-year-old Behçet's disease patient with pseudotumor of the right ventricle and multiple pulmonary emboli. Transthoracic echocardiography showed dilation of right atrium, right ventricle, and a mass in the right ventricle. Multislice computed tomography revealed a large, poorly defined mass infiltrating the groove and multiple pulmonary emboli. Surgery was performed with diagnostic and therapeutic intent. Following sternotomy, we identified a mass in the anterior wall of right ventricle, the outflow tract, and the inflow tract of right ventricle. The histopathologic analysis identified an inflammatory infiltrate composed of lymphocytes, plasma cells, and other inflammatory cells, without mitosis. And there were also some thrombus on top of the mass.

Predictive value of left ventricular dyssynchrony for short-term outcomes in three-vessel disease patients undergoing coronary artery bypass grafting with preserved or mildly reduced left ventricular ejection fraction.

Background and objective: Coronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF). Materials and methods: This study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes. Results: Short-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090-1.702); P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery. Conclusion: Pre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG.

Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats.

1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent studies suggest that pharmacological activation of AMPK inhibits cardiac hypertrophy. In the present study, we examined whether long-term treatment with metformin could attenuate ventricular hypertrophy in a rat model. The potential involvement of nitric oxide (NO) in the effects of metformin was also investigated. 2. Ventricular hypertrophy was established in rats by transaortic constriction (TAC). Starting 1 week after the TAC procedure, rats were treated with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were used to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10⁻6 mol/L) for 24 h under serum-free conditions in the presence or absence of metformin (10⁻³ mol/L), compound C (10⁻6 mol/L), L-NAME (10⁻6 mol/L) or their combination. The rate of incorporation of [³H]-leucine was determined, western blotting analyses of AMPK-eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were undertaken and the concentration of NO in culture media was determined. 4. Transaortic constriction resulted in significant haemodynamic dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident. Treatment with metformin improved haemodynamic function and significantly attenuated ventricular hypertrophy. Most of the effects of metformin were abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on haemodynamic function and ventricular hypertrophy in TAC rats. 5. In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME. The improvement in cardiac structure and function following metformin treatment was associated with enhanced phosphorylation of AMPK and eNOS and increased NO production. 6. The findings of the present study indicate that long-term treatment with metformin could attenuate ventricular hypertrophy induced by pressure overload via activation of AMPK and a downstream signalling pathway involving eNOS-NO.

[Smoking impairs endothelial function in ED patients].

OBJECTIVE: To determine whether smoking affects the endothelial function of young ED patients with no cardiovascular disease. METHODS: This study included 69 ED patients (21 smokers and 48 non-smokers) and 16 age-matched normal healthy controls. All underwent measurement of brachial artery flow-mediated vasodilation (FMD) and examinations of blood pressure, cholesterol, triglycerides and glucose. RESULTS: Brachial artery FMD was remarkably decreased in the ED patients, even more significantly in the smokers ([6.0 +/- 0.8]%) than in the non-smokers ([9.7 +/- 2.5]%) (P < 0.05), as compared with that in the normal healthy controls ([14.0 +/- 2. 5]%, P < 0.05). CONCLUSION: Endothelial function is impaired in ED patients, and is further damaged by smoking.

Association Between Dynamic Change of QT Interval and Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

Background: The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear. Methods: A total of 11,798 middle-aged subjects from the prospective, population-based cohort were included in this analysis. The QTc interval corrected for heart rate was measured on two occasions around 3 years apart in the Atherosclerosis Risk in Communities (ARIC) study. The ΔQTc interval was calculated by evaluating a change in QTc interval from visit 1 to visit 2. Results: After a median follow-up of 19.5 years, the association between the dynamic change of QTc interval and endpoints of death was U-shaped. The multivariate-adjusted hazard ratios (HRs) comparing subjects above the 95th percentile of Framingham-corrected ΔQTc (ΔQTcF) (≥32 ms) with subjects in the middle quintile (0-8 ms) were 2.69 (95% CI, 1.68-4.30) for SCD, 2.51 (1.68-3.74) for coronary heart disease death, 2.10 (1.50-2.94) for cardiovascular death, and 1.30 (1.11-1.55) for death from any cause. The corresponding HRs comparing subjects with a ΔQTcF below the fifth percentile (<-23 ms) with those in the middle quintile were 1.82 (1.09-3.05) for SCD, 1.83 (1.19-2.81) for coronary heart disease death, 2.14 (1.51-2.96) for cardiovascular death, and 1.31 (1.11-1.56) for death from any cause. Less extreme deviations of ΔQTcF were also associated with an increased risk of death. Similar, albeit weaker associations also were observed with ΔQTc corrected with Bazett's formula. Conclusions: A dynamic change of QTc interval is associated with increased mortality risk in the general population, indicating that repeated measurements of the QTc interval may be available to provide additional prognostic information.

Body mass index trajectories during mid to late life and risks of mortality and cardiovascular outcomes: Results from four prospective cohorts.

BACKGROUND: Our understanding of the weight-outcome association mainly comes from single-time body mass index (BMI) measurement. However, data on long-term trajectories of within-person changes in BMI on diverse study outcomes are sparse. Therefore, this study is to determine the associations of individual BMI trajectories and cardiovascular outcomes. METHODS: The present analysis was based on data from 4 large prospective cohorts and restricted to participants aged ≥45 years with at least two BMI measurements. Hazard ratios (HR) and 95% confidence intervals(95%CI) for each outcome according to different BMI trajectories were calculated in Cox regression models. FINDINGS: The final sample comprised 29,311 individuals (mean age 58.31 years, and 77.31% were white), with a median 4 BMI measurements used in this study. During a median follow-up of 21.16 years, there were a total of 10,192 major adverse cardiovascular events (MACE) and 11,589 deaths. A U-shaped relation was seen with all study outcomes. Compared with maintaining stable weight, the multivariate adjusted HR for MACE were 1.53 (95%CI 1.40-1.66), 1.26 (95%CI 1.16-1.37) and 1.08 (95%CI 1.02-1.15) respectively for rapid, moderate and slow weight loss; 1.01 (95%CI 0.95-1.07), 1.13 (95%CI 1.05-1.21) and 1.29 (95%CI 1.20-1.40) respectively for slow, moderate and rapid weight gain. Identical patterns of association were observed for all other outcomes. The development of BMI differed markedly between the outcome-free individuals and those who went on to experience adverse events, generally beginning to diverge 10 years before the occurrence of the events. INTERPRETATION: Our findings may signal an underlying high-risk population and inspire future studies on weight management. FUNDING: National Natural Science Foundation of China, Guangdong Natural Science Foundation.

Association Between Silent Myocardial Infarction and Long-Term Risk of Sudden Cardiac Death.

Background Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established. Methods and Results We examined 2 community-based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow-up visits that was not present at the baseline. The primary study end point was physician-adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow-up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81-7.10) and 3.80 (95% CI, 2.76-5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow-up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32-2.19) and 4.08 (95% CI, 3.29-5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18-3.23) and 3.99 (3.34-4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population-attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person-years. Addition of SMI significantly improved the predictive power for both SCD and non-SCD. Conclusions Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post-myocardial infarction therapy.

Assessment of Myocardial Dysfunction by Three-Dimensional Echocardiography Combined With Myocardial Contrast Echocardiography in Type 2 Diabetes Mellitus.

Background: We aimed to explore the value of combining real-time three-dimensional echocardiography (RT-3DE) and myocardial contrast echocardiography (MCE) in the left ventricle (LV) evaluating myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients. Patients and Methods: A total of 58 T2DM patients and 32 healthy individuals were selected for this study. T2DM patients were further divided into T2DM without microvascular complications (n = 29) and T2DM with microvascular complications (n = 29) subgroups. All participants underwent RT-3DE and MCE. The standard deviation (SD) and the maximum time difference (Dif) of the time to the minimum systolic volume (Tmsv) of the left ventricle were measured by RT-3DE. MCE was performed to obtain the perfusion measurement of each segment of the ventricular wall, including acoustic intensity (A), flow velocity (ß), and A·ß. Results: There were significant differences in all Tmsv indices except for Tmsv6-Dif among the three groups (all P < 0.05). After heart rate correction, all Tmsv indices of the T2DM with microvascular complications group were prolonged compared with the control group (all P < 0.05). The parameters of A, ß, and A·ß for overall segments showed a gradually decreasing trend in three groups, while the differences between the three groups were statistically significant (all P < 0.01). For segmental evaluation of MCE, the value of A, ß, and A·ß in all segments showed a decreasing trend and significantly differed among the three groups (all P < 0.05). Conclusions: The RT-3DE and MCE can detect subclinical myocardial dysfunction and impaired myocardial microvascular perfusion. Left ventricular dyssynchrony occurred in T2DM patients with or without microvascular complications and was related to left ventricular dysfunction. Myocardial perfusion was reduced in T2DM patients, presenting as diffuse damage, which was aggravated by microvascular complications in other organs.

B-type natriuretic peptide attenuates cardiac hypertrophy via the transforming growth factor-ß1/smad7 pathway in vivo and in vitro.

1. Previously, we showed that long-term treatment of rats after myocardial infarction (MI) with B-type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long-term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long-term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved. 2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 microg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10(-6) mol/L angiotensin (Ang) II for 48 h and cell surface area and [(3)H] incorporation were measured. Transforming growth factor (TGF)-beta1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription-polymerase chain reaction and western blotting. 3. Long-term BNP treatment dose-dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF-beta1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF-beta1/smad7 pathway, which were completely blocked by the cyclic GMP-dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10(-6) mol/L KT5823 for 48 h). 4. The results of the present study demonstrate that long-term treatment of rats with BNP dose-dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF-beta1 and upregulation of smad7 via PKG signalling. Long-term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.