Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia　- One-Year Data From the Global ETNA-AF Program.

Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients. Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA2DS2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups. Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Updated CRUSADE score to predict in-hospital bleeding: External validation in the Thai percutaneous coronary intervention registry.

BACKGROUND: The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) score has been recommended to predict in-hospital bleeding risk in non-ST segment elevation myocardial infarction (NSTEMI) patients. The evaluation of the CRUSADE risk score in Asian patients undergoing contemporary percutaneous coronary intervention (PCI) for NSTEMI is necessary. AIMS: We aimed to validate and update the CRUSADE score to predict in-hospital major bleeding in NSTEMI patients treated with PCI. METHOD: The Thai PCI registry is a large, prospective, multicenter PCI registry in Thailand enrolling patients between May 2018 and August 2019. The CRUSADE score was calculated based on 8 predictors including sex, diabetes, prior vascular disease (PVD), congestive heart failure (CHF), creatinine clearance (CrCl), hematocrit, systolic blood pressure, and heart rate (HR). The score was fitted to in-hospital major bleeding using the logistic regression. The original score was revised and updated for simplification. RESULTS: Of 19,701 patients in the Thai PCI registry, 5976 patients presented with NSTEMI. The CRUSADE score was calculated in 5882 patients who had all variables of the score available. Thirty-five percent were female, with a median age of 65.1 years. The proportion of diabetes, PVD, and CHF was 46%, 7.9%, and 11.2%, respectively. The original and revised models of the CRUSADE risk score had C-statistics of 0.817 (95% CI: 0.762-0.871) and 0.839 (95% CI: 0.789-0.889) respectively. The simplified CRUSADE score which contained only four variables (hematocrit, CrCl, HR, and CHF), had C-statistics of 0.837 (0.787-0.886). The calibration of the recalibrated, revised, and simplified model was optimal. CONCLUSIONS: The full and simplified CRUSADE scores performed well in NSTEMI treated with PCI in Thai population.

Door-to-device time and mortality in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: insight from real world data of Thai PCI Registry.

Background: Timely reperfusion therapy is recommended for patients with ST-segment elevation myocardial infarction (STEMI), and system delay <90 minutes and door-to-device (D2D) time <60 minutes are recommended by the 2017 ESC Guidelines for the management of STEMI patients and have been proposed as a performance measure for triaging patients for primary percutaneous coronary intervention (PCI). However, previous research produced contradictory results regarding the association between D2D time and mortality. Therefore, this study aimed to examine the associations between D2D time and mortality in Thailand. Methods: This cohort study included STEMI patients treated with primary PCI in 39 PCI centres in Thailand from February 27, 2018, to August 1, 2019. Patients were eligible if they met the following criteria: primary STEMI diagnosis, symptom onset within 12 hours, and ST-segment elevation of at least 0.1 mV in 2 or more contiguous leads (at least 0.2 mV in V1-V3) or a new left bundle branch block. Results: Within 12 hours of symptom onset, 3,874 patients underwent primary PCI. The median D2D time was 54 minutes [interquartile range (IQR) 29-90], and there was a significant difference between patients transferred from other hospitals (44 minutes, IQR 25-77, n=2,871) and patients presented directly to PCI centres (81 minutes, IQR 56-129, n=1,003) (P<0.001). Overall, in-hospital mortality was 7.8%. In a multivariable analysis, adjusting for other predictors of mortality and stratifying according to intervals of D2D time, cumulative in-hospital mortality was significantly higher in patients with a D2D time greater than 90 minutes [hazard ratio (HR) 1.5, 95% confidence interval (CI): 1.0-2.1, P=0.046] but not associated with D2D time shorter than 60 minutes (HR 1.2, 95% CI: 0.8-1.8, P=0.319). Conclusions: A D2D time greater than 90 minutes was related to in-hospital mortality in patients with STEMI treated with primary PCI, but a D2D time less than 60 minutes was not consistently associated with D2D time-improved survival in real-world, contemporary practice in Thailand.

Validation of the academic research consortium high bleeding risk definition in Thai PCI registry.

BACKGROUND: Bleeding following percutaneous coronary intervention (PCI) has important prognostic implications. The Academic Research Consortium (ARC) have identified a set of clinical criteria to standardize the definition of a high bleeding risk (HBR). Current study sought to externally validate the ARC definition for HBR patients in a contemporary real-world cohort. METHOD: This post hoc analysis included 22,741 patients undergoing PCI between May 2018 and August 2019 enrolled in Thai PCI Registry. The primary endpoint was the incidence of major bleeding at 12 months post index PCI. RESULTS: In total, 8678 (38.2%) and 14,063 (61.8%) patients were stratified to the ARC-HBR and non-ARC-HBR groups, respectively. Incidence of major bleeding was 3.3 and 1.1 per 1000 patients per month in the ARC-HBR group and the non-ARC-HBR group (HR 2.84 [95% CI: 2.39-3.38]; p < 0.001). Advanced age and heart failure met the 1-year major criteria performance goal of ≥4% major bleeding. The impact of HBR risk factors was incremental. HBR patients also experienced significantly higher rates of all-cause mortality (19.1% versus 5.2%, HR 4.00 [95% CI: 3.67-4.37]; p < 0.001) and myocardial infarction. The ARC-HBR score fairly performed in discriminating bleeding with C-statistic (95% CI) of 0.674 (0.649, 0.698). Updating the ARC-HBR by adding heart failure, prior myocardial infarction, non-radial access, female in the model significantly improved C-statistic of 0.714 (0.691, 0.737). CONCLUSIONS: The ARC-HBR definition could identify patients at increased risk not only for bleeding but also for thrombotic events, including all-cause mortality. Coexistence of multiple ARC-HBR criteria unveiled additive prognostic value.

External Validation of the ACUITY/HORIZON Bleeding Risk Score among Acute Coronary Syndrome Patients in Thai PCI Registry.

BACKGROUND: External validation is essential before implementing a predictive model in clinical practice. This analysis validated the performance of the ACUITY/HORIZON risk score in the most contemporary Thai PCI registry. METHODS: The ACUITY/HORIZON model was applied and validated externally in 12,268 ACS (acute coronary syndrome) patients. For revision and updating models, the regression coefficientd of all predictors were re-estimated and then additional predictors were stepwise selected from multivariate analysis. RESULTS: In-hospital bleeding defined by the BARC (Bleeding Academic Research Consortium) criteria was 1.3% (161 patients) and 2.3% (285 patients) by the ACUITY criteria. The calibration of both scales demonstrated overestimation of the original model with C-statistic values of 0.704 for ACUITY major bleeding and 0.793 for BARC 3 or 5 bleeding. For ACUITY major bleeding, the discriminatory power of the update model improved substantially when congestive heart failure (CHF), prior vascular disease as well as body mass index were considered. The update model demonstrated good calibration and C-statistic of 0.747 and 0.745 with no white blood cell (WBC) count. For BARC 3 or 5 bleeding, good calibration and discriminatory capacity could be observed when CHF and prior vascular disease were added in the update models, with an excellent C-statistic of 0.838, and a lower C-statistic value of 0.835 was obtained in the absence of WBC count. CONCLUSION: The ACUITY/HORIZON score was successfully validated in contemporary predictive and risk-adjustment models for PCI-related bleeding. The update models had good operating characteristics in patients from a real-world ACS population irrespective of bleeding definitions.

Patient Characteristics, Procedural Details, and Outcomes of Contemporary Percutaneous Coronary Intervention in Real-World Practice: Insights from Nationwide Thai PCI Registry.

Background: Percutaneous coronary intervention (PCI) practice and outcomes vary substantially in different parts of the world. The contemporary data of PCI in Asia are limited and only available from developed Asian countries. Objectives: To explore the pattern of practice and results of PCI procedures in Thailand as well as a temporal change of PCI practice over time compared with the registry from other countries. Methods: Thai PCI Registry is a prospective nationwide registry that was an initiative of the Cardiac Intervention Association of Thailand (CIAT). All cardiac catheterization laboratories in Thailand were invited to participate during 2018-2019, and consecutive PCI patients were enrolled and followed up for 1 year. Patient baseline characteristics, procedural details, equipment and medication use, outcomes, and complications were recorded. Results: Among the 39 hospitals participated, there were 22,741 patients included in this registry. Their mean age (standard deviation) was 64.2 (11.7) years and about 70% were males. The most common presentation was acute coronary syndrome (57%) with a high proportion of ST-elevation myocardial infarction (28%). Nearly two-thirds of patients had multivessel disease and significant left main stenosis was reported in 11%. The transradial approach was used in 44.2%. The procedural success rate was very high (95.2%) despite the high complexity of the lesions (56.9% type C lesion). The incidence of procedural complications was 5.3% and in-hospital mortality was 2.8%. Conclusion: Thai PCI Registry provides further insights into the current practice and outcomes of PCI in Southeast Asia. The success rate was very high, and the complications were very low despite the high complexity of the treated lesions.

Gut microbiota-generated metabolite, trimethylamine-N-oxide, and subclinical myocardial damage: a multicenter study from Thailand.

Plasma Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is mechanistically linked to cardiovascular disease (CVD) and adverse cardiovascular events. We aimed to examine the relationship between plasma TMAO levels and subclinical myocardial damage using high-sensitivity cardiac troponin-T (hs-cTnT). We studied 134 patients for whom TMAO data were available from the Cohort Of patients at a high Risk of Cardiovascular Events-Thailand (CORE-Thailand) registry, including 123 (92%) patients with established atherosclerotic disease and 11 (8%) with multiple risk factors. Plasma TMAO was measured by NMR spectroscopy. In our study cohort (mean age 64 ± 8.9 years; 61% men), median TMAO was 3.81 µM (interquartile range [IQR] 2.89-5.50 µM), and median hs-cTnT was 15.65 ng/L (IQR 10.17-26.67). Older patients and those with diabetic or hypertension were more likely to have higher TMAO levels. Plasma TMAO levels correlated with those of hs-cTnT (r = 0.54; p < 0.0001) and were significantly higher in patients with subclinical myocardial damage (hs-cTnT ≥ 14 ng/L; 4.48 µM vs 2.98 µM p < 0.0001). After adjusting for traditional risk factors, elevated TMAO levels remained independently associated with subclinical myocardial damage (adjusted odds ratio [OR]: 1.58; 95% CI 1.24-2.08; p = 0.0007). This study demonstrated that plasma TMAO was an independent predictor for subclinical myocardial damage in this study population.

Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.

AIMS: Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world. METHODS AND RESULTS: We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan. CONCLUSION: Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

PURPOSE: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. RESULTS: The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. CONCLUSIONS: VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

A clinical evaluation of the XIENCE V everolimus eluting stent in the treatment of patients with coronary artery disease: Result from Thailand Registry - XIENCE V performance evaluation (THRIVE study).

OBJECTIVE: To evaluate the 2-year clinical outcomes of XIENCETM V everolimus eluting stent (EES) for the treatment of coronary artery disease. BACKGROUND: Percutaneous coronary intervention with a drug eluting stent has become the preferred treatment in patients with coronary artery disease. Everolimus eluting stent had proven efficacy in randomized control trials but those trials may not represent daily practice of interventional cardiology. METHODS: The THRIVE study was a prospective, multicenter, real-world, single-arm registry. Included in the registry were 400 patients in Thailand with coronary artery disease suitable for treatment with the XIENCETM V. RESULTS: At 30 days, 1 year, and 2 years, the respective rate of all-cause mortality, myocardial infarction (MI), and target lesion revascularization (TLR) was 0.7, 1.0, and 0.5 %. 2.1, 2.1, and 1.0 %, and 2.2, 3.0, and 2.1 %. The cumulative rate for stent thrombosis was 1.6 % at 2 years. CONCLUSIONS: The THRIVE study demonstrated that use of EES yielded a rate for 2 years of major adverse cardiac events comparable to the randomized controlled trial of EES in the SPIRIT trials. This result supports the efficacy and safety of XIENCETM V everolimus eluting for daily interventional cardiology practice.

Demographics and Outcomes of Percutaneous Coronary Intervention in Thailand: Data from Thai Percutaneous Coronary Intervention Registry.

Background: Percutaneous coronary intervention (PCI) has been and continues to be standard treatment in patients with coronary artery disease. The data for demographic and outcomes in Thailand are limited. Objective: To study data and characteristics relating to patients, the procedure, and outcomes of percutaneous coronary intervention in the Thai population. Material and Method: The Thai Percutaneous Coronary Intervention Registry (TPCIR) was established in 2006, consisting of 27 hospitals in Thailand that perform the PCI procedure. All patients who underwent PCI between May 2006 and October 2006 in participating hospitals were asked to participate in this registry. Data was recorded in case record form and then entered into the web-based registry. Key variables include demographic data, risk factors, indications for PCI, outcomes, and complications. Results: Four thousand one hundred fifty six patients were enrolled; 69.2% were male. Average age of PCI patients was 62.7 years. Indications for PCI were ST segment elevation myocardial infarction (14%), Non-ST segment elevation acute coronary syndrome (37.3%), and stable coronary artery disease (48.7%). PCI was successfully performed in 92.5% of lesions or 89.6% of cases with in-hospital complications reported in 12% of cases. Conclusion: This was the first nationwide multi-center study of PCI in Thailand. The overall PCI procedure success rate was 92.5%.

Geographic variations in the PARADIGM-HF heart failure trial.

AIMS: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. METHODS AND RESULTS: We looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.6 (95% CI 11.7-15.7) WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. CONCLUSION: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Prognostic factors of in-hospital mortality in all comers with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: The prognostic factors of in-hospital mortality in all comers and unselected patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have not been well established. OBJECTIVE: To identify the predictive factors of in-hospital mortality in patients with STEMI undergoing primary PCI in a tertiary heart centre. METHODS: Between January 2008 and December 2011, all patients with STEMI undergoing primary PCI were retrospectively included in this study. Baseline characteristics and angiographic data were reviewed and recorded. The study endpoint was all-cause in-hospital mortality. RESULTS: Of the 541 patients included in the study, 63 (11.6%) died during hospitalisation. Cardiogenic shock at admission was recorded in 301 patients (55.6%) and 424 patients (78%) had multivessel disease. Median door-to-device time was 65 min. After adjustment for baseline variables, the factors associated with in-hospital mortality included age >60 years (OR 2.98, 95% CI 1.17 to 7.05; p=0.01), left ventricular ejection fraction <40% (OR 2.53, 95% CI 1.20 to 5.36; p=0.02), and final TIMI flow grade 0/1 (OR 20.55, 95% CI 3.49 to 120.94; p=0.001). CONCLUSIONS: Age, left ventricular function and final TIMI flow are significant predictors of adverse outcomes in unselected patients with STEMI undergoing primary PCI.

Blood transfusion after percutaneous coronary intervention and risk of subsequent adverse outcomes: a systematic review and meta-analysis.

OBJECTIVES: This study sought to define the prevalence and prognostic impact of blood transfusions in contemporary percutaneous coronary intervention (PCI) practice. BACKGROUND: Although the presence of anemia is associated with adverse outcomes in patients undergoing PCI, the optimal use of blood products in patients undergoing PCI remains controversial. METHODS: A search of EMBASE and MEDLINE was conducted to identify PCI studies that evaluated blood transfusions and their association with major adverse cardiac events (MACE) and mortality. Two independent reviewers screened the studies for inclusion, and data were extracted from relevant studies. Random effects meta-analysis was used to estimate the risk of adverse outcomes with blood transfusions. Statistical heterogeneity was assessed by considering the I(2) statistic. RESULTS: Nineteen studies that included 2,258,711 patients with more than 54,000 transfusion events were identified (prevalence of blood transfusion 2.3%). Crude mortality rate was 6,435 of 50,979 (12.6%, 8 studies) in patients who received a blood transfusion and 27,061 of 2,266,111 (1.2%, 8 studies) in the remaining patients. Crude MACE rates were 17.4% (8,439 of 48,518) in patients who had a blood transfusion and 3.1% (68,062 of 2,212,730) in the remaining cohort. Meta-analysis demonstrated that blood transfusion was independently associated with an increase in mortality (odds ratio: 3.02, 95% confidence interval: 2.16 to 4.21, I(2) = 91%) and MACE (odds ratio: 3.15, 95% confidence interval: 2.59 to 3.82, I(2) = 81%). Similar observations were recorded in studies that adjusted for baseline hematocrit, anemia, and bleeding. CONCLUSIONS: Blood transfusion is independently associated with increased risk of mortality and MACE events. Clinicians should minimize the risk for periprocedural transfusion by using available bleeding-avoidance strategies and avoiding liberal transfusion practices.

A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure.

AIMS: Although active-controlled trials with renin­angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. METHODS AND RESULTS: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34­50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21­44%; P < 0.0001) and heart failure hospitalization (49%, 39­58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15­39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27­48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16­45%; P < 0.0001) for cardiovascular death, 46% (33­56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11­39%; P < 0.0001) for all-cause mortality. CONCLUSION: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Non-BMPR2 mutation heritable pulmonary arterial hypertension in Southeast Asia.

A 29-year-old Thai man presented with progressive dyspnea and evidence of pulmonary hypertension. Computed tomography was negative for pulmonary embolism. Cardiac catheterization confirmed the diagnosis of pulmonary arterial hypertension (mean pulmonary artery pressure 54 mm Hg, left ventricular end-diastolic pressure 4 mm Hg, and pulmonary vascular resistance 25 Wood units) without an intracardiac shunt. Two family members had been previously diagnosed with pulmonary hypertension. There was no evidence of left heart disease or respiratory disorders. Based on the definite diagnosis of pulmonary hypertension in 3 family members, heritable pulmonary arterial hypertension was confirmed. Genetic testing indicated no BMPR2 mutation.

Diagnostic accuracy of coronary CT angiography in patients after coronary bypass surgery: evaluation of grafts and native coronary arteries.

OBJECTIVE: To evaluate the diagnostic accuracy in the assessment of both grafts and native coronary arteries in patients after coronary artery bypass grafts (CABG) by coronary CT angiography (CCTA) in comparison to invasive conventional coronary angiography (CCA). MATERIAL AND METHOD: CCTA was performed in 54 symptomatic post-CABG patients. Two independent, blinded observers assessed all grafts and native coronary arteries for significant stenosis. CCA served as a reference standard One hundred seventy two graft segments, 156 distal coronary run-offs, 314 grafted coronary segments, and 18 non-grafted coronary segments were analyzed RESULTS: The diagnostic accuracy of CCTA for exclusion or detection of significant stenosis in venous grafts and non-grafted segments of native coronary arteries was 100%. Sensitivity, specificity, and positive and negative predictive values were all 100%. Sensitivity, specificity, and positive and negative predictive values to detect significant stenosis were 100%, 98%, 91%, and 100%, respectively, in arterial grafts, 100%, 99%, 75%, and 100%, respectively, in distal runoffs, and 100%, 87%, 99%, and 100%, respectively, in grafted segments of native coronary arteries. CONCLUSION: Non-invasive coronary CT angiography provides high diagnostic accuracy for evaluation of both bypass grafts and native coronary arteries, although, CCTA is more effective in evaluation of bypass grafts as compared to heavily calcified native coronary arteries.

Left atrial coagulation activity in patient with mitral stenosis in sinus rhythm.

OBJECTIVE: Anticoagulation therapy is strongly recommended in all patients with mitral stenosis (MS) in atrial fibrillation (AF) but this treatment is controversial in patients in sinus rhythm (SR). The objective of the present study was to investigate the coagulation activity in patients with MS in sinus rhythm compared to those in atrial fibrillation. MATERIAL AND METHOD: The authors studied the levels of biochemical markers of thrombin generation (thrombin-anti-thrombin [TAT] complex,fibrinogen, and factor XIII) and fibrinolysis (D-dimer) in specimens of blood from the atria in 35 consecutive patients with moderate to severe MS (18 in sinus rhythm and 17 in AF) who underwent percutaneous balloon mitral valvotomy. RESULTS: The levels coagulation factors in left atrium in patients with MS in SR and AF were thrombin-anti-thrombin complex = 77.21 +/- 8.87 mg/L vs. 73.48 +/- 7.78 mg/L, p = 0.755, fibrinogen = 356.57 +/- 41.86 mg/L vs. 271.62 +/- 22.47 mg/L, p = 0.089, factor XIII = 139.88 +/- 8.96 mg/L vs. 123.42 +/- 6.24 mg/L, p = 0.152, and D-dimer = 846.14 +/- 137.84 mg/L vs. 693.88 +/- 164.67 mg/L, p = 0.481. Levels of coagulation activities did not correlate with the left atrial size. CONCLUSION: This present study demonstrates that coagulation activity is not different whether they are in SR or in AF and suggests that anticoagulation therapy should be considered in these patients.

Correlation of causes and outcomes in stroke in the young.

BACKGROUND: We studied the association of causes and stroke outcome of stroke in the young in Thailand. METHODS: A retrospective study was performed at Srinagarind Hospital, Khon Kaen University, Thailand. All patients under 45 years of age who were diagnosed with stroke between 1996 and 2010 and who had complete workups for causes of stroke in the young were enrolled. Stroke outcome was defined as favorable or nonfavorable at approximately 1 year of follow-up. If the patient had normal functional ability or mild disability but the patient was fully employed, the outcome was classified as favorable. Clinical features of strokes and the potential stroke risk factors were compared between the favorable and nonfavorable groups. RESULTS: Eighty-five patients were enrolled. About half of patients were male (47 patients; 55.3%). The mean age (SD) was 35.9 (6.2) years. Three-fourths of male patients had a stroke after 30 years of age, while female patients developed stroke in all age ranges equally. More than half of patients (45 patients; 52.9%) had cardiac causes of stroke. Rheumatic mitral stenosis accounted for 68% (31 patients), and 45% (14 patients) had atrial fibrillation. There were 64 patients (79%) who had a favorable outcome. Cardiac causes, particularly mitral stenosis and alcohol intake, were significantly associated with a nonfavorable outcome. CONCLUSIONS: Stroke in the young generally has a favorable outcome. Factors associated with a nonfavorable outcome of stroke in the young were cardiac abnormalities and alcohol intake. A prospective study to evaluate the association of causes and outcome is needed.