The Role of Cardiac Fibrosis in Diabetic Cardiomyopathy: From Pathophysiology to Clinical Diagnostic Tools.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to inadequate insulin secretion, resistance, or both. The cardiovascular complications of DM are the leading cause of morbidity and mortality in diabetic patients. There are three major types of pathophysiologic cardiac remodeling including coronary artery atherosclerosis, cardiac autonomic neuropathy, and DM cardiomyopathy in patients with DM. DM cardiomyopathy is a distinct cardiomyopathy characterized by myocardial dysfunction in the absence of coronary artery disease, hypertension, and valvular heart disease. Cardiac fibrosis, defined as the excessive deposition of extracellular matrix (ECM) proteins, is a hallmark of DM cardiomyopathy. The pathophysiology of cardiac fibrosis in DM cardiomyopathy is complex and involves multiple cellular and molecular mechanisms. Cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction (HFpEF), which increases mortality and the incidence of hospitalizations. As medical technology advances, the severity of cardiac fibrosis in DM cardiomyopathy can be evaluated by non-invasive imaging modalities such as echocardiography, heart computed tomography (CT), cardiac magnetic resonance imaging (MRI), and nuclear imaging. In this review article, we will discuss the pathophysiology of cardiac fibrosis in DM cardiomyopathy, non-invasive imaging modalities to evaluate the severity of cardiac fibrosis, and therapeutic strategies for DM cardiomyopathy.

Effect of the Ligation and Reperfusion Timeframe on Maximal Ischemia-Reperfusion Injury in Diverse Rat Models.

Background: Little is known about the effect that different time sequences for coronary ligation and reperfusion have on ischemic-reperfusion (IR) injury. Objective: To investigate the relationship between the extent of IR injury and the timeframe for coronary ligation/reperfusion in three animal models. Methods: Three rat models were used: normal Sprague-Dawley rats, diabetes mellitus (DM) rats, and fat rats. The rats in each model were divided into four groups based on the coronary ligation period (L): 30, 60, 120, and 180 min, and then divided into seven sub-groups based on the reperfusion period (R): 0, 30, 60, 120, 180, 270, and 360 min. R0 was the IR injury baseline for each sub-group. The hearts were harvested and stained with Evans blue and 2,3,5-triphenyl tetrazolium chloride dye to distinguish the different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The difference between each subgroup and baseline (R0) for the necrotic area/AAR was calculated. Results: In the normal rats, the highest IR injury differences compared with the baseline group occurred at L120, with a reperfusion time of > 180 min. The highest IR injury difference compared to the baseline group occurred at L30, with a reperfusion time of > 180 min in the DM rats and at L60R270, L120R180 in the fat rats. Conclusions: IR injury, as induced by different coronary ligation and reperfusion time intervals, had diverse expression profiles in the different animal models. Optimal animal models with optimal coronary ligation/reperfusion protocols to achieve maximal IR injury will affect the results and interpretation of future studies.

Sarcomeres Morphology and Z-Line Arrangement Disarray Induced by Ventricular Premature Contractions through the Rac2/Cofilin Pathway.

The most common ventricular premature contractions (VPCs) originate from the right ventricular outflow tract (RVOT), but the molecular mechanisms of altered cytoskeletons of VPC-induced cardiomyopathy remain unexplored. We created a RVOT bigeminy VPC pig model (n = 6 in each group). Echocardiography was performed. The histopathological alternations in the LV myocardium were analyzed, and next generation sequencing (NGS) and functional enrichment analyses were employed to identify the differentially expressed genes (DEGs) responsible for the histopathological alternations. Finally, a cell silencing model was used to confirm the key regulatory gene and pathway. VPC pigs had increased LV diameters in the 6-month follow-up period. A histological study showed more actin cytoskeleton disorganization and actin accumulation over intercalated disc, Z-line arrangement disarray, increased ß-catenin expression, and cardiomyocyte enlargement in the LV myocardium of the VPC pigs compared to the control pigs. The NGS study showed actin cytoskeleton signaling, RhoGDI signaling, and signaling by Rho Family GTPases and ILK Signaling presented z-scores with same activation states. The expressions of Rac family small GTPase 2 (Rac2), the p-cofilin/cofilin ratio, and the F-actin/G-actin ratio were downregulated in the VPC group compared to the control group. Moreover, the intensity and number of actin filaments per cardiomyocyte were significantly decreased by Rac2 siRNA in the cell silencing model. Therefore, the Rac2/cofilin pathway was found to play a crucial role in the sarcomere morphology and Z-line arrangement disarray induced by RVOT bigeminy VPCs.

The implications of catheter ablation for solitary atrial flutter in preventing stroke risk: a nationwide population-based cohort study.

AIMS: The implications of ablation for atrial fibrillation in preventing stroke are controversial, and no studies have investigated whether ablation prevents ischaemic stroke (IS) in atrial flutter (AFL). METHODS AND RESULTS: This study analysed data contained in the Taiwan National Health Insurance Research Database for 16 765 patients with a first diagnosis of solitary AFL during 2001-2013. Eligible patients were divided into two groups according to whether or not they had received ablation. Propensity score matching (PSM) was performed to mitigate the effects of potential confounding factors. The primary outcome was occurrence of IS during follow-up. After 1:2 PSM, the analysis included 1037 patients in the ablation group and 2074 patients in the non-ablation group. The incidence of IS was lower in the ablation group compared to the non-ablation group [subdistribution hazard ratio (SHR) 0.61, 95% confidence interval (CI) 0.41-0.90] during the 2-year follow-up period but not thereafter (SHR 1.03, 95% CI 0.72-1.48). When grouping by stroke history, it revealed that ablation affected the incidence of stroke in patients without history of stroke (SHR 0.59, 95% CI 0.38-0.91) but not in patients with history of stroke. When each group was stratified by CHA2DS2-VASc score, ablation lowered the incidence of stroke in patients with CHA2DS2-VASc ≤3 (SHR 0.31, 95% CI 0.16-0.60) but not in patients with CHA2DS2-VASc ≥4 in the initial 2-year follow-up. CONCLUSION: The different incidence of IS in patients with/without ablation indicates that ablation reduces the risk of IS in AFL patients.

Inhibition of Notch Signaling Alleviated Diabetic Macrovasculopathy in an In Vitro Model.

BACKGROUND: Interactions between endothelial cells and vascular smooth muscle cells (VSMCs) through the Notch signal pathway causing diabetic microvasculopathy have been reported. OBJECTIVES: The purpose of this study was to investigate whether the effect of high glucose on VSMCs through the Notch-2 signaling pathway could induce extracellular matrix (ECM) accumulation, VSMC proliferation and migration and thus directly mediate diabetic macrovasculopathy. METHODS: Rat smooth muscle cells (SV40LT-SMC Clone HEP-SA cells) were cultured in different concentrations of D-glucose to evaluate the impact of high glucose on ECM accumulation including fibronectin and collagen I measured by Western blot analysis, and on VSMC proliferation and migration evaluated by MTT assay and wound healing assay. The expression of Notch-2 intra-cellular domain (Notch-2 ICD) protein was also checked in high glucose-stressed VSMCs. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of γ-secretase, was used to modulate the Notch-2 signaling pathway. RESULTS: High glucose (D-glucose 25 mM) induced fibronectin and collagen I expressions in VSMCs, promoted VSMC proliferation/migration, and enhanced the expression of Notch-2 ICD. DAPT inhibited Notch-2 signal to abolish the expressions of fibronectin and collagen I in VSMCs, and also prevented the proliferation/migration of VSMCs under high glucose (D-glucose 25 mM) stress. CONCLUSIONS: Our study suggests that high glucose can enhance the Notch-2 signaling pathway thereby directly mediating diabetic macrovasculopathy. Blocking the Notch-2 signaling pathway decreased fibronectin and collagen I expressions secreted by VSMCs, and reduced the proliferation and migration of VSMCs under high glucose stress. Inhibition of Notch-2 signaling represents a promising target for treating diabetic macrovasculopathy.

The Unraveled Link Between Antiviral Therapy and Heart Failure Hospitalization in Chronic Hepatitis C Virus Infection　- A Nationwide Cohort Study.

BACKGROUND: Although hepatitis C virus (HCV) is a known risk factor for cardiovascular disease, whether antiviral therapy (AVT) can reduce heart failure (HF) hospitalizations is unknown.Methods and Results:In this population-based cohort study, we used data from the Taiwan National Health Insurance Research Database to evaluate the effect of interferon-based therapy (IBT) on cardiovascular events in patients with chronic HCV infection. Clinical outcomes evaluated included HF hospitalizations; a composite of acute myocardial infarction, ischemic stroke, and peripheral artery disease; all-cause death; and cardiovascular death. Of 83,229 eligible patients with chronic HCV infection, we compared 16,284 patients who received IBT with untreated subjects after propensity score matching. Patients who received IBT were less likely to be hospitalized for HF compared with untreated subjects (incidence density.ID, 0.9 vs. 1.5 events per 103person-years; hazard ratio.HR, 0.58; 95% confidence interval.CI, 0.42-0.79; P=0.001). Compared with untreated subjects, the treated group had significantly lower risk of composite vascular events (ID, 3.7 vs. 5.0 events per 103person-years; P<0.001), all-cause death (ID, 5.6 vs. 17.2 events per 103person-years; P<0.001), and cardiovascular death (ID, 0.2 vs. 0.6 events per 103person-years; P=0.001). CONCLUSIONS: AVT for chronic HCV infection might offer protection against HF hospitalizations, critical vascular events, and cardiovascular death beyond known beneficial effects.

Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB.

Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios ( R BNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for R BNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and R BNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: R BNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations.

Optimal Duration of Coronary Ligation and Reperfusion for Reperfusion Injury Study in a Rat Model.

BACKGROUND: Reperfusion injury (RI) has an important impact on the clinical prognosis for patients with acute myocardial injury who had their coronary blood flow reestablished. However, no studies to date have investigated the timeframe of coronary occlusion and reperfusion effects on RI. METHODS: A total of 100 rats were divided into 4 groups based on the coronary ligation period: 30, 60, 120, and 180 min, and each group was further divided into 5 subgroups with different reperfusion periods: 0, 30, 60, 120, and 180 min. R0 was the baseline of each subgroup. All animals received the same protocols for designed ligation and reperfusion periods. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to distinguish different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The differences of the ratios of the necrotic area to AAR between each subgroup and baseline were further averaged to calculate an overall value of each heart. RESULTS: The relative RI percentages showed significant differences (0.8 ± 2.3%, 4.9 ± 3.3%, 10.8 ± 3.1%, and 20.3 ± 3.6% respectively, p < 0.001) at different time points of reperfusion but not at different time points of ligation (p = 0.593). The effects of different time courses in RI showed that the L120R180 group (43.4 ± 2.3%) had the highest RI difference with the baseline group. CONCLUSIONS: Maximal RI occurred at the timeframe of L120R180 in our animal model. This result may be utilized to assess the substantial benefits of RI therapies in an experimental rat model setting.

Platelet Glycoprotein IIb/IIIa Inhibitor Tirofiban Ameliorates Cardiac Reperfusion Injury.

There are many published articles on the effects of the antithrombolytic function of platelet glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa inhibitors) in myocardial infarction. However, few studies have explored the effects and optimal concentration of tirofibans in diminishing the extent of myocardial reperfusion injury (RI).Rats received 120 minutes of coronary ligation and 180 minutes of reperfusion. The rats were then divided into 7 groups based on the concentration of tirofiban administered intravenously 30 minutes prior to coronary reperfusion to the end of reperfusion. The ratio of myocardial necrotic area to area at risk (AAR), and myocardial malondialdehyde (MDA) and plasma myeloperoxidase (MPO) activities were measured. The apoptotic index (AI) was the percentage of myocytes positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) out of all myocytes stained by 4', 6-diamidino-2-phenylindole (DAPI).The ratio of myocardial necrotic area to AAR significantly decreased in all tirofiban subgroups. The MDA activity for tirofiban concentrations of 2 and 5 ug/kg/minute showed a slight reduction. MPO activity was significantly decreased at a tirofiban concentration of 2 ug/kg/minute. The AI was significantly decreased at a tirofiban concentration of ≥ 0.4 ug/kg/minute.The results indicate that a tirofiban can significantly ameliorate the cardiac RI and myocyte apoptosis in rats.

The effects of gout on left atrial volume remodelling: a prospective echocardiographic study.

OBJECTIVE: The aim of the present study was to investigate the effect of gout on left ventricular (LV) diastolic function and left atrial volume (LAV). METHODS: A total of 173 patients were divided into four groups: control (n = 35), asymptomatic hyperuricaemia (n = 30), gouty arthritis without tophi (n = 58) and gouty tophi (n = 50). Patients underwent a comprehensive Doppler echocardiography examination to evaluate LV volume, systolic and diastolic function and LAV and function. RESULTS: Serum uric acid levels were not significantly different in the asymptomatic hyperuricaemia, gouty arthritis without tophi and gouty tophi groups. However, the ratio of the transmitral and myocardial peak early diastolic velocities (E/e') and LAV index (LAVi) progressively increased from the control group to the gouty tophi group. The tophi group had significantly higher E/e' [10.5 (s.d. 3.2) vs 8.6 (s.d. 2.1), P = 0.008] and larger maximal, pre-contraction and minimal LAVi [29.6 ml/m(2) (s.d. 9.9) vs 20.1 ml/m(2) (s.d. 4.8); 19.1 ml/m(2) (s.d. 8.5) vs 11.5 ml/m(2) (s.d. 3.4); 9.6 ml/m(2) (s.d. 4.2) vs 6.1 ml/m(2) (s.d. 2.2); all P < 0.001] than the control group. By binary logistic analysis, maximal LAVi was an independent predictor for the development of tophi in gout patients, with an odds ratio of 1.068 (95% CI 1.02, 1.118; P = 0.005). CONCLUSION: The severity of gout had a significant effect on LV diastolic dysfunction and LA enlargement in gout patients. Additionally, a high maximal LAVi predicted the development of tophi and may be a predictor of adverse cardiovascular events related to LA and LV remodelling in this clinical setting.

Association between viral hepatitis and metabolic syndrome in lung function impairment: A Taiwan community-based study.

OBJECTIVES: Metabolic syndrome (MetS) and hepatitis C virus (HCV) are associated with a higher risk of impaired pulmonary function (iPF). This study aimed to investigate the relationships among MetS, iPF, and viral hepatitis. METHODS: This community-based study enrolled participants undergoing annual health check-ups in southern Taiwan between March and December 2019. We performed multivariable logistic regression analyses adjusted for demographics and characteristics to identify the factors associated with iPF. RESULTS: A total of 2337 participants completed examinations, of whom 928 (39.7%) had iPF. The participants with iPF were elderly (68.8 ± 12.8 years old) and predominately female (63%). MetS increased the risk of iPF (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.27-1.81, p < 0.001). Beyond age (OR 1.03, 95% CI 1.02-1.04) and smoking (OR 1.309, 95% CI 1.004-1.705), female sex (OR 0.74, 95% CI 0.59-0.93) and high education level (OR 0.96, 95% CI 0.94-0.98, p < 0.001) protected against iPF. HCV was not significantly associated with iPF (OR 1.17, 95% CI 0.90-1.52, p = 0.235) in multivariable analysis. MetS was associated with a higher risk of iPF in the non-HBV/HCV group (OR 1.86, 95% CI 1.54-2.26) and HBV alone group (OR 3.44, 95% CI 1.89-6.28), but not in the HCV alone group (OR 1.02, 95% CI 0.64-1.62). DISCUSSION: MetS was an independent predictor of iPF, especially the restrictive type, and had different effects in the HBV/non-viral hepatitis and HCV groups. Female sex and education were inversely associated with iPF.

Using intermittent pneumatic compression therapy to improve quality of life for symptomatic patients with infrapopliteal diffuse peripheral obstructive disease.

BACKGROUND: Although the acute effect of intermittent pneumatic compression (IPC) therapy had been documented for patients with symptomatic peripheral arterial obstructive disease (PAOD), its efficacy in improving quality of life (QOL), especially for those with infrapopliteal diffuse lesions, remains unclear. METHODS AND RESULTS: Thirty-one patients with infrapopliteal diffuse or multiple segmental lesions were enrolled in the study. Based on receipt of IPC therapy (3 h daily for 3 months), patients were allocated to a study (n=23) or control (n=8) group. The 6-min walking test, transcutaneous oxygen tension (TcPO2), and QOL evaluated with the Short-Form 36 questionnaire were measured at the beginning and end of the study. In the QOL analysis, scores for physical functioning, physical and emotional role functioning, bodily pain, and general and mental health showed significant changes after IPC therapy. In the 6-min walking test, duration, and the initial and absolute claudication distances were significantly increased in the study group. The TcPO2 also significantly increased in the distal end of the target limb after IPC therapy. CONCLUSIONS: Patients at high risk for amputation with infrapopliteal diffuse or multiple segmental lesions can improve their walking ability, TcPO2 of the target limb and QOL after IPC therapy.

Cardioselective Versus Nonselective ß-Blockers After Myocardial Infarction in Adults With Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To investigate which types of ß-blockers have better efficacy and safety profiles in patients with concomitant chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI) to address concerns about use of ß-blockers in COPD. METHODS: We identified 65,699 patients with COPD prescribed ß-blockers after first MI in the Taiwan National Health Insurance Research Database between January 1, 2001, and December 31, 2013. Comparisons were performed using the inverse probability of treatment weighting method. The primary outcome was all-cause mortality; secondary outcomes were heart failure hospitalization, major adverse cardiac and cerebrovascular event (MACCE), and major adverse pulmonary event (MAPE). RESULTS: A total of 14,789 patients prescribed ß-blockers were enrolled, of whom 7247 (49.0%) used cardioselective ß-blockers and 7542 (51.0%) used nonselective ß-blockers. The cardioselective group had lower incidence rates of mortality (hazard ratio [HR], 0.93; 95% CI, 0.89 to 0.96), MACCE (HR, 0.96; 95% CI, 0.93 to 0.998), heart failure hospitalization (subdistribution HR, 0.84; 95% CI, 0.78 to 0.91), and MAPE (HR, 0.94; 95% CI, 0.90 to 0.98) at the end of follow-up after weighting. Similar results were also found in subgroup analysis between those prescribed bisoprolol and those prescribed carvedilol. CONCLUSION: Patients prescribed a cardioselective ß-blocker may have a lower incidence of all-cause mortality, MACCE, heart failure hospitalization, and MAPE than those prescribed a nonselective ß-blocker. Cardioselective ß-blocker treatment during hospitalization and continuing after discharge appears to be superior to nonselective ß-blocker treatment in patients with COPD after MI.

The Impact of Hepatitis C Virus, Metabolic Disturbance, and Unhealthy Behavior on Chronic Kidney Disease: A Secondary Cross-Sectional Analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a higher risk of chronic kidney disease (CKD). This study investigates the relationship among HCV, CKD, and understudied confounders, such as unhealthy behaviors and metabolic disturbances. METHODS: This cross-sectional study was conducted as part of a community health promotion program in an HCV endemic area of Taiwan from June to December 2019. Multivariable logistic regression analyses adjusted for demographic and clinical characteristics were performed to investigate the association between CKD and HCV seropositivity. RESULTS: Of 2387 participants who underwent health check-ups, the mean age was 64.1 years old; females predominated (63.2%), and 306 (12.8%) subjects were seropositive for HCV. CKD, defined as a lower estimated glomerular filtration rate (eGFR) was associated with unhealthy dietary habits, metabolic syndrome, and HCV. Less frequent exercise, higher waist circumference (WC) and HbA1c all affected risk of CKD; HCV increased risk of CKD by 44% compared to non-HCV (OR 1.44, 95% confidence interval (CI) 1.05-1.98) in the multivariable analysis. In the HCV group, lower eGFR was also significantly associated with the severity of metabolic syndrome (MetS) (median eGFR was 86.4, 77.1, and 64.5 mL/min/1.73 m2 for individuals with three and five MetS components, respectively). CONCLUSIONS: Beyond metabolic disturbance and irregular exercise, HCV seropositivity is independently associated with CKD in a community survey. Healthy lifestyle promotion might protect against renal function decline in HCV; however, the mechanisms underlying the association need further large-scale investigation.

Venous Thromboembolism and Critical Limb Events in Patients with Atrial Fibrillation: A Nationwide Population-Based Cohort Study.

Little is known about whether venous thromboembolism (VTE) causes worse critical limb events in populations with atrial fibrillation (AF). A retrospective cohort study using claims data from Taiwan's National Health Insurance program between 2001 and 2013 compared AF patients with or without VTE. Outcomes were percutaneous transluminal angioplasty (PTA), amputation, systemic thromboembolism, all-cause mortality, cardiovascular death, ischemic stroke, and acute myocardial infarction. Patients (n = 316,817) with newly diagnosed AF were analyzed; of those, 2514 (0.79%) had VTE history. After inverse probability of treatment weighting, a history of VTE was significantly associated with higher risks of PTA (3.3 vs 2.2%; subdistribution hazard ratio [SHR] 1.47; 95% confidence interval [CI] 1.17-1.84); above knee amputation (0.7 vs 0.3%; HR 2.15; 95% CI 1.10-4.21); systemic thromboembolism (5.8 vs 3.9%; SHR 1.48; 95% CI 1.21-1.80); all-cause mortality (53 vs 46.4%; HR 1.20, 95% CI 1.12-1.29); and cardiovascular death (34.8 vs 29.4%; HR 1.25, 95% CI 1.14-1.36). In conclusion, VTE might increase the risk of critical lower limb events (PTA and above-knee amputation), systemic thromboembolism, and mortality in the AF population. However, current data cannot confirm a causal relationship between VTE and clinical outcomes in this population.

Statins to prevent pacing-induced cardiomyopathy: Evidence from the bench applied to clinical studies.

BACKGROUND: Pacing-induced cardiomyopathy is an undesired outcome in patients with atrioventricular block (AVB), and our animal model showed lipotoxic cardiomyopathy after pacing. OBJECTIVES: The purpose of this study was to explore the mechanisms and clinical outcomes of statins in AVB patients receiving pacing. METHODS: Rat ventricular cardiomyocytes were treated with atorvastatin, liver X receptor (LXR) agonist, and LXR antagonist during pacing. Pigs were divided into 3 groups: right ventricular pacing, pacing with concomitant atorvastatin treatment, and sham control. Clinically, we enrolled 1717 AVB patients who had received a permanent pacemaker from Chang Gung Memorial Hospital Medical database. The primary outcome (cardiovascular death or heart failure [HF] hospitalization) and individual outcome were compared between statin and nonstatin groups after inverse probability of treatment weighting. RESULTS: Lipid accumulation in rat cardiomyocytes by pacing was significantly reduced by treatment with LXR agonist and atorvastatin, whereas LXR antagonist counteracted the atorvastatin effect on lipid expression. Left ventricular ejection fraction (LVEF) was significantly lower in the AVB pig pacing group compared to the group concomitantly treated with atorvastatin. Moreover, lipid accumulation and fibronectin expression were significantly ameliorated by concomitant treatment with atorvastatin. In the clinical study, the statin group had a significantly lower risk of the primary outcome event (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.56-0.84), less HF hospitalization (HR 0.45; 95% CI 0.30-0.67), and higher LVEF than the nonstatin group. CONCLUSION: In experimental models, atorvastatin ameliorated lipid accumulation in cardiomyocytes and fibrosis in left ventricular myocardium induced by pacing. Clinically, treatment with statins was associated with less HF hospitalization and cardiovascular death in AVB patients receiving pacemaker therapy.

Prognostic value of QT dispersion change following primary percutaneous coronary intervention in acute ST elevation myocardial infarction.

This study analyzed the corrected QT dispersion (cQTd) before and at 24 hours after successful primary percutaneous coronary intervention (PCI) in 81 patients with single coronary artery disease and acute ST elevation myocardial infarction. Major cardiovascular events (MACE) at 1 year were defined as death, nonfatal myocardial infarction, life-threatening arrhythmias, and heart failure hospitalization. The cQTd before primary PCI was significantly longer in patients without MACE than in patients with MACE (73.1 ± 29.3 versus 56.3 ± 25.2 msec, P = 0.026). The cQTd at 24 hours after primary PCI was significantly shorter in patients without MACE than in patients with MACE (38.4 ± 20.8 versus 50.8 ± 28.7 msec, P = 0.045). Thus, the absolute cQTd change was significantly higher in patients without MACE compared to patients with MACE (P = 0.001). By multivariate analysis, absolute cQTd change was an independent predictor for the development of MACE, with an odds ratio of 1.498 for each 10-msec decrement in absolute cQTd change (95 percent confidence interval, 1.157 to 1.939, P = 0.002). In conclusion, the absolute cQTd change after primary PCI was an independent predictor of the development of MACE in patients with single vessel disease and acute ST elevation myocardial infarction.

Coronary phenotypes in patients with erectile dysfunction and silent ischemic heart disease: a pilot study.

INTRODUCTION: Accumulated evidence shows that erectile dysfunction (ED) may be a precursor of coronary artery disease (CAD). AIMS: The purpose of this study was to explore the differences in coronary phenotypes between patients with ED and patients with angina pectoris. METHODS: The study enrolled 30 ED patients (study group) and 120 age-matched angina patients who had no ED (control group). All patients had angiographically documented CAD. MAIN OUTCOME MEASURES: The differences in demographic characteristics, biochemical profiles and coronary characteristics between the study and control groups were compared. RESULTS: Diabetes mellitus (DM) and obesity defined by body mass index were more common in the study group than in the control group. The mean number of lesions and mean number of vessels with evidence of CAD were significantly different between the study and control groups (2.3 ± 0.1 vs. 2.2 ± 0.1, P < 0.001; 2.0 ± 0.2 vs. 1.8 ± 0.1, P < 0.001). The distribution of vessel involvement was similar between the groups, except for more common involvement of the ramus in the study group. There were no differences in distribution of lesion sites between the two groups. The control group had a higher percentage of type A stenotic lesions than the study group (16.3% vs. 2.9%, P = 0.004). Significant differences were also observed in type C lesions (52.9% in study group vs. 38.0% in control group, P = 0.026). Fewer calcified, irregular, and bifurcated lesions were present in the study group compared to control. CONCLUSIONS: This study documented coronary phenotypes in ED patients without symptomatic CAD. Although the artery size hypothesis and ED had well been thought to be a precursor of CAD, the severity of coronary lesions in these patients was not more benign than that observed in angina pectoris patients who have no ED.

Independent determinants of coronary artery disease in erectile dysfunction patients.

INTRODUCTION: There is growing evidence of a link between erectile dysfunction (ED) and coronary artery disease (CAD). AIMS: The purpose of this study was to explore the independent determinants of CAD in ED outpatients. METHODS: This study enrolled 243 patients, ranging in age from 21 to 81 years old, suffering from ED as diagnosed by the International Index of Erectile Function (IIEF) scores. All patients underwent exercise stress tests or thallium-201 single-photon emission computed tomography perfusion imagings. Based on examination results, patients were divided into study (22 patients with a positive finding) and control groups (221 patients with a negative finding). MAIN OUTCOME MEASURES: The differences of demographic characteristics, biochemical profiles, pro-inflammatory and inflammatory markers, and echocardiographic characteristics between study and control group were compared. RESULTS: The age, presence of DM and current smoking status were significant high in the study group. A significant lower high-density lipoprotein (HDL) cholesterol level, a higher percentage of HDL cholesterol level < 40 mg/dL, and a higher apo-lipoprotein B/A1, high sensitive C-reactive protein (hs-CRP) and homocysteine found in the study group. The Framingham cardiac risk scores, the ratio of mitral inflow velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging (E/Et), the ratio of E/Et > or = 15, the value of carotid intima-media thickness (IMT), and IMT > or = 1 mm were higher in study group than in the control group. In stepwise multiple logistic regression analysis, a high waist-to-hip ratio (WHR), high IMT, high E/Et, hs-CRP levels, LDL cholesterol > or = 130 mg/dL, smoking status, and the presence of DM and metabolic syndrome (MS) were independent determinants of CAD in ED patients. CONCLUSIONS: This study first shows the independent determinants of CAD in ED outpatients. This novel finding may improve the screening of low-risk ED patients for CAD.

Scrutiny of cardiovascular risk factors by assessing arterial stiffness in erectile dysfunction patients.

PURPOSE: Erectile dysfunction (ED) is an early sign of vascular dysfunction. Studies have reported a correlation between arterial stiffness and cardiovascular events. The objective of this study was to evaluate the association among different criteria for assessing arterial stiffness and cardiovascular risk factors in ED patients. METHODS: Assessment of pulse wave velocity (PWV), pulse pressure (PP), ratio of mitral inflow velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging (E/Et), and intima-medial thickness (IMT) were performed in 200 ED patients. RESULTS: Linear statistical analysis of the coronary artery disease risk factors revealed that PWV, PP and E/Et were positively correlated with age, duration of diabetes mellitus (DM), and systolic and diastolic blood pressures. PWV and E/Et were positively correlated with waist circumference and number of metabolic syndrome (MS) components. For category-wise analysis, the PWV, PP and E/Et were higher in patients with DM, hypertension and MS. Multiple regression analysis showed that the independent determinants for PWV comprised age, DM, hypertension, and MS; for PP comprised age, hypertension, and MS; for E/Et comprised age and MS; and for IMT comprised only DM. CONCLUSIONS: Thus, PWV, PP and E/Et may be employed as markers to identify ED patients with potential cardiovascular risk factors, including MS and obesity.