Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction.

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1-5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1-5) had the best predictive value. MSE slope 1-5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1-5 was a good predictor of postinfarct LV systolic impairment.

Impact of Selection Preference on Longer-Term Outcomes between Bioresorbable Vascular Scaffold versus Everolimus-Eluting Stent for True Lumen Tracking-Recanalized Chronic Total Occlusion.

Creation of sizable subintima during intervention for chronic total occlusions (CTO) could lead to the key selection preference of metallic stents rather than bioresorbable vascular scaffolds (BVS) and then possibly deviate the outcome comparisons in real-world studies. By including recanalized CTO with true lumen tracking, we tested if any selection preference remained and compared the outcomes between everolimus-eluting stent (EES) and BVS implantation.Among 211 consecutive CTO interventions with true lumen tracking from August 2014 to April 2018 when BVS was available, we compared the clinical and interventional features between 28 patients with BVS and 77 patients with EES implantation. With propensity score matching and a median follow-up of 50.5 (37.3-60.3) months, we further assessed 25 patients with BVS and 25 with EES for target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target lesion revascularization).Multivariate analyses showed that BVS was still favored in the presence of LAD CTO (odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.0-11.7) and an average scaffold/stent size ≥ 3 mm (OR = 10.5, 95% CI = 3.0-37.3). EES was preferred for lesions with a J-CTO score ≥ 3 (OR = 19.3, 95% CI = 3.4-110.8) and multivessel intervention necessary at index procedure (OR = 11.3, 95% CI = 1.9-67.3). With matched comparisons, the TVF-free survival of EES was better than that of BVS for CTO recanalization (P = 0.049 by log-rank test) at long-term follow-up.Even with true lumen tracking techniques, selection bias remained substantial when determining either device for CTO implantation. The matched comparison of outcomes suggested the unfavorable longer-term impacts of the first generation of BVS on CTO lesions.

New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism.

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m2; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m2; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.

Serum myostatin level is associated with myocardial scar burden by SPECT myocardial perfusion imaging.

BACKGROUND: Myostatin is a negative regulator of skeletal muscle and myocardial mass. The relationship between myocardial ischemia and scar burden and levels of myostatin has not been established. METHODS: We enrolled symptomatic patients with heart failure (HF) with a left ventricular ejection fraction (LVEF) < 45 % and controls (LVEF ≥ 45 %). Serum levels of myostatin were measured. Single-photon emission computed tomography (SPECT) imaging was interpreted, and summed scores of 17 stress and rest image segments in 5-point scale produced the summed stress score (SSS) and summed rest score (SRS), respectively. The summed difference score (SDS) was calculated as the difference between the SSS and SRS. RESULTS: Ninety-six patients with HF and 103 controls were enrolled. The levels of myostatin were higher in the HF group. In linear regression analysis, myostatin level was positively correlated with SSS (ß coefficient = 6.840, p = 0.013) and SRS (ß coefficient = 5.557, p = 0.026), but not correlated with SDS. The areas under the receiver operating characteristic curves of myostatin levels for SSS ≥ 8 and SSS ≥ 13 were 0.6813 ± 0.04854 (p < 0.001) and 0.7498 ± 0.04402 (p < 0.001), respectively. CONCLUSION: Serum levels of myostatin were correlated with the extent of myocardial scarring as defined by SPECT imaging. Serum levels of myostatin may be a predictor of myocardial scar burden.

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis.

Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

Small chemical compounds Y16 and Rhosin can inhibit calcium sensitization pathway in vascular smooth muscle cells of spontaneously hypertensive rats.

BACKGROUND/PURPOSE: The small-molecule compounds Y16 and Rhosin can inhibit the activation of leukemia-associated Rho guanine nucleotide exchange factor (LARG) and small G-protein RhoA, respectively, in breast cancer cells and inhibit their growth and migration. However, it remains unclear whether they have inhibitory effects on the vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHRs). METHODS: Primary cultured VSMCs from SHRs were treated with different concentrations of Y16 or Y16 plus Rhosin for 24 h, followed by 10-min stimulation with 10-7 M angiotensin II (Ang II). The cells were then harvested, and the total protein was extracted. The co-immunoprecipitation method, Western blot analysis, and MTT assay were performed to determine the LARG-RhoA interaction, the protein levels of RhoA and MYPT1, and cell viability, respectively. RESULTS: Y16 dose-dependently inhibited the LARG-RhoA complex formation induced by Ang II. With 50 µM of Y16, the effect of inhibition was statistically significant. Y16 also reduced the formation of phospho-MYPT1 stimulated by Ang II. With 5 µM of Y16, the inhibitory effect was statistically significant. When 25 µM of Y16 and 25 µM of Rhosin were combined, the inhibitory effect on LARG-RhoA interaction was statistically significant. When Y16 and Rhosin were combined, a significantly reduced concentration could effectively inhibit MYPT1 phosphorylation (2.5 µM compared with 5 µM for Y16 alone). CONCLUSION: Treating SHR VSMCs with Y16 can suppress the activation of LARG, prevent LARG binding to RhoA, and decrease the phosphorylation of MYPT1, thus weakening the activation of the calcium (Ca2+) sensitization pathway in SHR VSMCs.

Digoxin-amiodarone Combination is Associated With Excess All-cause Mortality in Patients With Atrial Fibrillation.

Combination use of digoxin and other medications might lead to worse outcomes in patients with atrial fibrillation (AF). We sought to investigate whether digoxin-amiodarone combination would lead to worse outcome than digoxin alone in patients with AF. Adult patients with AF and received digoxin treatment from random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included. Baseline characteristics including risk factors and medications were matched by propensity score (PS) in those with and without addition of amiodarone treatment. A total of 5,040 AF patients taking digoxin therapy was included. PS matching identified 1,473 patients receiving digoxin-amiodarone combination and 2,660 patients receiving digoxin with a median follow-up of 1,331 days. Digoxin-amiodarone combination was associated with increased all-cause mortality (adjusted hazard ratio (HR): 1.640, 95% confidence interval (CI): 1.470-1.829, P < 0.001). The risk of mortality increased regardless of duration of combination. Risk of sudden cardiac death was not increased in the combination group (HR: 1.304, 95% CI: 1.049-1.622, P = 0.017). Death due to non-arrhythmic cardiac disease, cerebrovascular disease, and other vascular disease were higher in the combination group than the digoxin group. In conclusion, in patients with AF, digoxin-amiodarone combination therapy is associated with excess mortality than digoxin alone.

Reduction of blood pressure elevation by losartan in spontaneously hypertensive rats through suppression of LARG expression in vascular smooth muscle cells.

BACKGROUND/PURPOSE: This study sought to elucidate the mechanism by which losartan inhibits blood pressure (BP) elevation in spontaneously hypertensive rats (SHRs). METHODS: Four-week-old Wistar-Kyoto (WKY) rats and SHRs were either treated with losartan (20 mg/kg/day) for 8 weeks or served as untreated controls. BP was measured by the tail-cuff method. At 12 weeks, isometric contraction of the aortic rings of the rats was evaluated with a force transducer and recorder. The mRNA and protein levels of the target Rho guanine nucleotide exchange factors (RhoGEFs), and the extent of myosin phosphatase target subunit 1 (MYPT-1) phosphorylation in the aorta, were determined using quantitative real-time polymerase chain reaction (qPCR) assay and Western blot analysis. RESULTS: The BP of the four-week-old SHRs did not differ from that of the age-matched WKY rats, whereas the BP of the twelve-week-old control group SHRs was higher than that of the control group WKY rats. Losartan treatment, however, inhibited BP elevation in both rat strains, doing so to a greater extent in the treatment group SHRs. The contractile force in response to angiotensin II of the aortic rings from the SHRs treated with losartan was significantly lower than that of the aortic rings from the non-treated SHRs. The protein expression of leukemia-associated RhoGEF (LARG) was significantly higher in the non-treated SHRs compared to the non-treated WKY rats. CONCLUSION: The study results showed that the reduction of BP elevation by losartan in SHRs occurs through the suppression of LARG expression and MYPT-1 phosphorylation in vascular smooth muscle cells.

Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response.

Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance. Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA). Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests. Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.

The Taiwan Heart Registries: Its Influence on Cardiovascular Patient Care.

Taiwanese heart registries for the main cardiovascular diseases have been conducted in the past 10 years, with the goal of examining the quality of cardiovascular patient care, which cannot be guaranteed by the universal Taiwan National Health Insurance. The results show suboptimal adherence to guideline recommendations. Door-to-balloon time and dual antiplatelet therapy use in acute coronary syndrome, standard medications for management of heart failure, low-density lipoprotein cholesterol levels in dyslipidemia, anticoagulant agent use in atrial fibrillation, and the understanding of sudden arrhythmia death syndrome were all found to be inadequate. However, all were improved, either by changing National Health Insurance policy or through continuous education for physicians and patients. Thus, specific cardiovascular disease registries could help examine the status of real-world practice, find inadequacies in guideline implementation and understanding of rare diseases, facilitate lobbying to policy makers and education for physicians and patients, and influence and improve cardiovascular patient care.

Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-The ALEVENT clinical trial.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. OBJECTIVES: We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. METHODS: We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive protein levels of ≥1.5 mg/L, and LVDD, diagnosed by conventional and tissue Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. RESULTS: Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant improvement of early mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site (Nominal change for E/Emedial: -5.01 ± 6.36 vs 1.80 ± 6.59 for atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SRIVR, 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). CONCLUSIONS: In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671).

Serial heart rhythm complexity changes in patients with anterior wall ST segment elevation myocardial infarction.

Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were lower throughout the chronic stage. Area 6-20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity.

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES: Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. MATERIALS AND METHODS: Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. RESULTS: A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617-0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007-0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033-0.362, P = 0.0003). CONCLUSION: Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD.

Primary prevention of atrial fibrillation with beta-blockers in patients with end-stage renal disease undergoing dialysis.

Current evidence suggests that beta-blocker lower the risk of development of atrial fibrillation (AF) and in-hospital stroke after cardiac surgery. This study was to assess whether beta-blockers could decrease incidence of new-onset AF in patients with end stage renal disease (ESRD). We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score matching and Cox's proportional hazards regression model were used to estimate hazard ratios (HRs) for new-onset AF. Among 100066 patients, 41.7% received beta-blockers. After a median follow-up of 1500 days, the incidence of new-onset AF significantly decreased in patients treated with beta-blockers (HR = 0.483, 95% confidence interval = 0.437-0.534). The prevention of new-onset AF was significantly better in patients taking longer duration of beta-blockers therapy (P for time trend <0.001). The AF prevention effect remains robust in subgroup analyses. In conclusion, beta-blockers seem effective in the primary prevention of AF in ESRD patients. Hence, beta-blockers may be the target about upstream treatment of AF.