Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important global public health issue, but its epidemiology and outcomes in low-income and middle-income countries remain largely unknown. We aim to comprehensively describe the incidence, process of care, and outcomes of OHCA in China. METHODS: In the prospective, multicentre, population-based Baseline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA) registry study, participating sites were selected from both urban and rural areas in all seven geographical regions across China. All patients with OHCA assessed by emergency medical service (EMS) staff were consecutively enrolled from Aug 1, 2019, to Dec 31, 2020. Patients with suspected cardiac arrest assessed by bystanders whose return of spontaneous circulation was achieved without the need for defibrillation or EMS personnel cardiopulmonary resuscitation were excluded. Patients with all key variables missing were excluded, including resuscitation attempt, age, sex, witnessed status, cause, all process of care indicators, and all outcome measures. In this analysis, we included data for EMS agencies serving 25 monitoring sites (20 urban and five rural) that included the entire serving population, data for the whole of 2020, and at least 50 OHCA patients in 2020. Data were collected and reported using the Utstein template. We calculated the crude incidence of EMS-assessed OHCA in 2020. We also report data on baseline characteristics (including sex, cause, location of OHCA, and presence of shockable rhythm), process of care (including EMS response time, cardiopulmonary resuscitation, defibrillation, and advanced life support), and outcomes of non-traumatic OHCA between Aug 1, 2019, and Dec 31, 2020, including survival and survival with favourable neurological outcomes at discharge or 30 days, and at 6 and 12 months. FINDINGS: Of 115·1 million people served by the 25 participating sites, 132 262 EMS-assessed patients with OHCA were enrolled, and resuscitation was attempted for 42 054 (31·8%) patients between Aug 1, 2019, and Dec 31, 2020. The crude incidence of EMS-assessed OHCA was 95·7 per 100 000 population (95% CI 95·6-95·8) in 2020. Among 38 227 individuals with non-traumatic OHCA, 25 958 (67·9%) were male, 30 282 (79·2%) had a cardiac arrest at home, 32 523 (85·1%) had a presumed cardiac cause, and 2297 (6·0%) presented with an initial shockable rhythm. 4049 (11·5%) of 35 090 patients with an unwitnessed or bystander-witnessed OHCA received dispatcher-assisted cardiopulmonary resuscitation and 7121 (20·3%) received bystander cardiopulmonary resuscitation; only 14 (<0·1%) patients were assessed by bystanders with an automated external defibrillator. The median EMS response time was 12 min (IQR 9-16). At hospital discharge or 30 days, 441 (1·2%) of 38 227 survived, 304 (0·8%) survived up to 6 months, and 269 (0·7%) up to 12 months. At hospital discharge or 30 days, 309 (0·8%) survived with favourable neurological outcomes, 257 (0·7%) had favourable neurological outcomes at 6 months, and 236 (0·6%) at 12 months. INTERPRETATION: Our findings revealed a high burden of EMS-assessed OHCA with a low proportion of resuscitation attempts. The suboptimal implementation of chain of survival and unsatisfactory prognosis call for national efforts to improve the care and outcomes of patients with OHCA in China. FUNDING: The National Science & Technology Fundamental Resources Investigation Program of China, the State Key Program of the National Natural Science Foundation of China, Taishan Pandeng Scholar Program of Shandong Province, the Key Research & Development Program of Shandong Province, the Interdisciplinary Young Researcher Groups Program of Shandong University, the Clinical Research Center of Shandong University, the ECCM Program of Clinical Research Center of Shandong University, and the Natural Science Foundation of Shandong Province.

The impact of non-optimum temperatures, heatwaves and cold spells on out-of-hospital cardiac arrest onset in a changing climate in China: a multi-center, time-stratified, case-crossover study.

Background: Out-of-hospital cardiac arrest (OHCA) is a time-critical and fatal medical emergency that has been linked to non-optimal temperatures. However, the future burden of OHCA due to non-optimal temperatures, heatwaves, and cold spells under climate change has not been well evaluated. Methods: We conducted a time-stratified case-crossover study in 15 Northern Chinese cities throughout 2020 to estimate the exposure-response relationships of non-optimal temperatures, heatwaves, and cold spells with hourly OHCA onset in hot and cold seasons. We obtained future daily average temperatures by using 20 general circulation models under two greenhouse gas emission scenarios: one with certain emission control and the other with relaxed control. Lastly, we projected the change of OHCA burden under these two climate scenarios. Findings: We analyzed a total of 29,671 OHCA patients and found that high temperatures and heatwaves as well as low temperatures and cold spells were all significantly associated with an increased risk of OHCA onset. Under the scenario of uncontrolled emissions, the attributable fraction (AF) of OHCA due to high temperatures and heatwaves would increase by 4.94% and 6.99% from the 2010s to 2090s, respectively. The AF due to low temperatures would decrease by 1.27% by the 2090s and the effects of cold spells were projected to be marginal after the 2050s. Under a medium emission control scenario, the upward trend of heat-related OHCA burden would become flat, and the decline in cold-related OHCA burden would also slow down. Interpretation: Our study provides evidence of significant morbidity risk and burden of OHCA associated with global warming across Northern China. Our findings indicate that the increase in OHCA burden attributable to heat could not be offset by the decrements attributable to cold, emphasizing the importance of mitigation policies for limiting global warming and reducing the associated risks of OHCA onset. Funding: National Science & Technology Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), National Key R&D Program of China (2020YFC1512700, 2020YFC1512705, 2020YFC1512703), Key R&D Program of Shandong Province (2021ZLGX02, 2021SFGC0503), Natural Science Foundation of Shandong Province (ZR2021MH231), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), the Interdisciplinary Young Researcher Groups Program of Shandong University (2020QNQT004), ECCM Program of Clinical Research Center of Shandong University (2021SDUCRCA001, 2021SDUCRCA002), foundation from Clinical Research Center of Shandong University (2020SDUCRCB003), National Natural Science Foundation of China (82272240).

Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.

Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.

Efforts to Improve Survival Outcomes of Out-of-Hospital Cardiac Arrest in China: BASIC-OHCA.

BACKGROUND: Establishing registries to collect demographic characteristics, processes of care, and outcomes of patients with out-of-hospital cardiac arrest (OHCA) can better understand epidemiological trends, measure care quality, and identify opportunities for improvement. This study aimed to describe the design, implementation, and scientific significance of a nationwide registry-the BASIC-OHCA (Baseline Investigation of Out-of-Hospital Cardiac Arrest)-in China. METHODS: BASIC-OHCA was designed as a prospective, multicenter, observational, population-based study. The BASIC-OHCA registry was developed based on Utstein templates. BASIC-OHCA includes all OHCA patients confirmed by emergency medical services (EMS) personnel regardless of age, sex, or cause. Patients declared dead at the scene by EMS personnel for any reasons are also included. To fully characterize an OHCA event, BASIC-OHCA collects data from 3 sources-EMS, the receiving hospital, and patient follow-up-and links them to form a single record. Once data entry is completed and quality is checked, individual identifiers are stripped from the record. RESULTS: Currently, 32 EMS agencies in 7 geographic regions contribute data to BASIC-OHCA. They are distributed in the urban and rural areas, covering ≈9% of the population of mainland China. Data collection started on August 1, 2019. By July 31, 2020, a total of 92 913 EMS-assessed OHCA patients were enrolled. Among 28969 (31.18%) EMS-treated OHCAs, the mean age was 65.79±17.36 years, and 68.35% were males. The majority of OHCAs (76.85%) occurred at home or residence. A shockable initial rhythm was reported in 5.43% of patients. Any return of spontaneous circulation, survival to hospital discharge, and favorable neurological outcome at hospital discharge were 5.98%, 1.15%, and 0.83%, respectively. CONCLUSIONS: BASIC-OHCA is the first nationwide registry on OHCA in China. It can be used as a public health surveillance system and as a platform to produce evidence-based practices to help identify opportunities for improvement. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03926325.

Factors associated with in-hospital mortality from free wall rupture after acute myocardial infarction.

BACKGROUND: Free wall rupture is a fatal and emergency complication of acute myocardial infarction. The factors associated with in-hospital mortality from free wall rupture remain unclear. OBJECTIVES: To investigate the factors associated with in-hospital mortality from free wall rupture. METHODS: We performed a single-center, retrospective study. We enrolled 111 consecutive patients with free wall rupture following acute myocardial infarction who were admitted to Fuwai Hospital from January 2005 to May 2021. The primary endpoint was in-hospital death. Clinical characteristics, laboratory data, and treatment modalities associated with in-hospital mortality were analyzed. RESULTS: Eighty-seven of the 111 study participants died in hospital. Multivariate Cox regression analysis showed that pericardiocentesis (hazard ratio [HR] 0.296, 95% confidence interval [CI] 0.094-0.929, p = 0.037), pericardial effusion at admission (HR 0.083, 95% CI 0.025-0.269, p<0.001), time interval between acute myocardial infarction and free wall rupture (HR 0.670, 95% CI 0.598-0.753, p<0.001), and previous myocardial infarction (HR 0.046, 95% CI 0.010-0.208, p<0.001) were independently associated with in-hospital mortality. CONCLUSIONS: Pericardiocentesis, pericardial effusion at admission, the acute myocardial infarction to free wall rupture time, and previous myocardial infarction are associated with a lower rate of in-hospital mortality from free wall rupture after acute myocardial infarction.

Sex-related prognostic value of systolic blood pressure on admission in critically ill patients with acute decompensated heart failure.

The present study aimed to evaluate sex-specific association between admission systolic blood pressure (SBP) and in-hospital prognosis in patients with acute decompensated heart failure (ADHF) admitted to intensive care unit (ICU). In this retrospective, observational study, 1268 ADHF patients requiring intensive care were consecutively enrolled and divided by sex. Patients were divided into three subgroups according to SBP tertiles: high (≥ 122 mmHg), moderate (104-121 mmHg) and low (< 104 mmHg). The primary endpoint was either all-cause mortality, cardiac arrest or utilization of mechanical support devices during hospitalization. Female patients were more likely to be older, have poorer renal function and higher ejection fractions (p < 0.001). The C statistics of SBP was 0.665 (95%CI 0.611-0.719, p < 0.001) for men and 0.548 (95% CI 0.461-0.634, p = 0.237) for women, respectively. Multivariate analysis demonstrated that admission SBP as either a continuous (OR = 0.984, 95% CI 0.973-0.996) or a categorical (low vs. high, OR = 3.293, 95% CI 1.610-6.732) variable was an independent predictor in male but the risk did not statistically differ between the moderate and high SBP strata (OR = 1.557, 95% CI 0.729-3.328). In female, neither low (OR = 1.135, 95% CI 0.328-3.924) nor moderate (OR = 0.989, 95% CI 0.277-3.531) SBP had a significant effect on primary endpoint compared with high SBP strata. No interaction was detected between left ventricular ejection fraction (LVEF) and SBP (p for interaction = 0.805). In ADHF patients admitted to ICU, SBP showed a sex-related prognostic effect on primary endpoint. In male, lower SBP was independently associated with an increased risk of primary endpoint. Conversely, in female, no relationship was observed.

A national effort to improve outcomes for in-hospital cardiac arrest in China: The BASeline Investigation of Cardiac Arrest (BASIC-IHCA).

Background: In-hospital cardiac arrest (IHCA) is a common clinical event with poor outcomes. Former IHCA registries in China were local, inconsistent in data reporting, and lacked attention to the process of care. Therefore, we designed and implemented the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA), the first national IHCA registry in China. Methods: BASIC-IHCA is a prospective, multicenter, observational study with a nationwide surveillance network covering urban and rural hospitals from seven geographic regions of China. IHCA patients were enrolled continuously, and data were collected from medical records by investigators at participating hospitals. Key variables referring to the updated Utstein Template included patient information, event variables, process of care, and outcomes. Follow-up was conducted by telephone interview to obtain details on long-term survival and neurological status. Results: Thirty-two urban hospitals and eight rural hospitals from twenty-nine provinces in seven geographic regions of China participated in BASIC-IHCA. The starting time of enrollment ranged from July 1, 2019, to January 1, 2020. By December 31, 2020, 35,451 IHCAs were enrolled in all participating hospitals, of which 19,493 (55%) received CPR, with a predominance of males (65%) and a median age of 65 years. Conclusion: BASIC-IHCA is the first national registry for IHCA in China. It will describe the epidemiology and outcomes of IHCA from a nationwide perspective, with a particular focus on details of the process of care for quality improvement. Meanwhile, it will help to facilitate the standardization of IHCA-related data reporting in China.

Prognosis Implication of N-Terminal Pro-B-Type Natriuretic Peptide in Adult Patients With Acute Myocarditis.

Background: The aim of this study is to investigate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in assessing the poor outcomes of adult patients with acute myocarditis. Methods: A total of 170 adult patients with available NT-proBNP information were included in the study. They were grouped according to quartiles of NT-proBNP concentrations at admission. Baseline and follow-up information was collected. Thirty-day major adverse cardiac events (MACE) were death and heart transplantation. Long-term MACE included all-cause death, heart transplantation, re-hospitalization due to heart failure, sustained ventricular arrhythmia, and myocarditis relapse. Results: During a median follow-up of 3.8 years, patients in the highest NT-proBNP quartile suffered from the highest risk both of 30-day and long-term MACE (P < 0.001 by log-rank test). Multivariate analysis showed that apart from left ventricular ejection fraction (LVEF), an increased baseline NT-proBNP > 3,549 pg/mL (hazard ratio 3.535, 95% CI 1.316-9.499, P = 0.012) and NT-proBNP > 7,204 pg/mL (hazard ratio 22.261, 95% CI 1.976-250.723, P = 0.012) was independent predictor of long-term and 30-day MACE, respectively. Conclusions: Higher baseline NT-proBNP level was an independent predictor of poor outcomes in adult patients with acute myocarditis. Therefore, NT-proBNP may serve as a useful biomarker for risk stratification in acute myocarditis patients.

Fulminant Giant Cell Myocarditis vs. Lymphocytic Myocarditis: A Comparison of Their Clinical Characteristics, Treatments, and Outcomes.

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM). Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0-10.2) mg/L vs. 13.6 (12.6-14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0-3.2) ng/ml vs. 14.6 (3.0-64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0-61.5) IU/L vs. 997.0 (50.0-3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761-0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213-0.9964). Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

A new scoring system for predicting short-term outcomes in Chinese patients with critically-ill acute decompensated heart failure.

BACKGROUND: Acute decompensated heart failure (ADHF) contributes millions of emergency department (ED) visits and it is associated with high in-hospital mortality. The aim of this study was to develop and validate a multiparametric score for critically-ill ADHF patients. METHODS: In this single-center, retrospective study, a total of 1268 ADHF patients in China were enrolled and divided into derivation (n = 1014) and validation (n = 254) cohorts. The primary endpoint was any in-hospital death, cardiac arrest or utilization of mechanical support devices. Logistic regression model was preformed to identify risk factors and build the new scoring system. The assigning point of each parameter was determined according to its ß coefficient. The discrimination was validated internally using C statistic and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test. RESULTS: We constructed a predictive score based on six significant risk factors [systolic blood pressure (SBP), white blood cell (WBC) count, hematocrit (HCT), total bilirubin (TBIL), estimated glomerular filtration rate (eGFR) and NT-proBNP]. This new model was computed as (1 × SBP < 90 mmHg) + (2 × WBC > 9.2 × 109/L) + (1 × HCT ≤ 0.407) + (2 × TBIL > 34.2 µmol/L) + (2 × eGFR < 15 ml/min/1.73 m2) + (1 × NTproBNP ≥ 10728.9 ng/ml). The C statistic for the new score was 0.758 (95% CI 0.667-0.838) higher than APACHE II, AHEAD and ADHERE score. It also demonstrated good calibration for detecting high-risk patients in the validation cohort (χ2 = 6.681, p = 0.463). CONCLUSIONS: The new score including SBP, WBC, HCT, TBIL, eGFR and NT-proBNP might be used to predict short-term prognosis of Chinese critically-ill ADHF patients.

Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure.

Objective: We aimed to evaluate the association between plasma big endothelin-1 (ET-1) at admission and short-term outcomes in acute decompensated heart failure (ADHF) patients. Methods: In this single-center, retrospective study, a total of 746 ADHF patients were enrolled and divided into three groups according to baseline plasma big ET-1 levels: tertile 1 (<0.43 pmol/L, n = 250), tertile 2 (between 0.43 and 0.97 pmol/L, n = 252), and tertile 3 (>0.97 pmol/L, n = 244). The primary outcomes were all-cause death, cardiac arrest, or utilization of mechanical support devices during hospitalization. Logistic regression analysis and net reclassification improvement approach were applied to assess the predictive power of big ET-1 on short-term outcomes. Results: During hospitalization, 92 (12.3%) adverse events occurred. Etiology, arterial pH, lactic acid, total bilirubin, serum creatine, serum uric acid, presence of atrial fibrillation and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with plasma big ET-1 level, whereas systolic blood pressure, serum sodium, hemoglobin, albumin, and estimated glomerular filtration rate were negatively correlated. In multivariate logistic regression, tertile 3 compared with tertile 1 had a 3.68-fold increased risk of adverse outcomes [odds ratio (OR) = 3.681, 95% confidence interval (CI) 1.410-9.606, p = 0.008]. However, such adverse effect did not exist between tertile 2 and tertile 1 (OR = 0.953, 95% CI 0.314-2.986, p = 0.932). As a continuous variable, big ET-1 level was significantly associated with primary outcome (OR = 1.756, 95% CI 1.413-2.183, p < 0.001). The C statistic of baseline big ET-1 was 0.66 (95% CI 0.601-0.720, p < 0.001). Net reclassification index (NRI) analysis showed that big ET-1 provided additional predictive power when combining it to NT-proBNP (NRI = 0.593, p < 0.001). Conclusion: Elevated baseline big ET-1 is an independent predictor of short-term adverse events in ADHF patients and may provide valuable information for risk stratification.

Clinical characteristics and prognosis of heart failure with mid-range ejection fraction: insights from a multi-centre registry study in China.

BACKGROUND: Heart failure (HF) with mid-range ejection fraction (EF) (HFmrEF) has attracted increasing attention in recent years. However, the understanding of HFmrEF remains limited, especially among Asian patients. Therefore, analysis of a Chinese HF registry was undertaken to explore the clinical characteristics and prognosis of HFmrEF. METHODS: A total of 755 HF patients from a multi-centre registry were classified into three groups based on EF measured by echocardiogram at recruitment: HF with reduced EF (HFrEF) (n = 211), HFmrEF (n = 201), and HF with preserved EF (HFpEF) (n = 343). Clinical data were carefully collected and analyzed at baseline. The primary endpoint was all-cause mortality and cardiovascular mortality while the secondary endpoints included hospitalization due to HF and major adverse cardiac events (MACE) during 1-year follow-up. Cox regression and Logistic regression were performed to identify the association between the three EF strata and 1-year outcomes. RESULTS: The prevalence of HFmrEF was 26.6% in the observed HF patients. Most of the clinical characteristics of HFmrEF were intermediate between HFrEF and HFpEF. But a significantly higher ratio of prior myocardial infarction (p = 0.002), ischemic heart disease etiology (p = 0.004), antiplatelet drug use (p = 0.009), angioplasty or stent implantation (p = 0.003) were observed in patients with HFmrEF patients than those with HFpEF and HFrEF. Multivariate analysis showed that the HFmrEF group presented a better prognosis than HFrEF in all-cause mortality [p = 0.022, HR (95%CI): 0.473(0.215-0.887)], cardiovascular mortality [p = 0.005, HR (95%CI): 0.270(0.108-0.672)] and MACE [p = 0.034, OR (95%CI): 0.450(0.215-0.941)] at 1 year. However, no significant differences in 1-year outcomes were observed between HFmrEF and HFpEF. CONCLUSION: HFmrEF is a distinctive subgroup of HF. The strikingly prevalence of ischemic history among patients with HFmrEF might indicate a key to profound understanding of HFmrEF. Patients in HFmrEF group presented better 1-year outcomes than HFrEF group. The long-term prognosis and optimal medications for HFmrEF require further investigations.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy.

BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy. METHODS: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy. RESULTS: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified. CONCLUSIONS: We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement.

AIMS: To investigate whether genetic variants of CYP2C9 and VKORC1 have different effects on the dose of warfarin in 180 Han Chinese patients who were recruited from the Fu Wai Hospital. All were on maintenance treatment with stable daily warfarin doses for a period of at least 3 months. METHODS: DNA was isolated and genotyped using a Warfarin dosage Prediction Kit for single nucleotide polymorphisms (SNPs) of CYP2C9 and VKORC1. RESULTS: The VKORC1 and CYP2C9*3 polymorphisms are significantly associated with warfarin maintenance dosages. Patients with AG&GG genotype in VKORC1 needed higher doses than those with AA genotypes (4.55 ± 1.27 mg/ day vs. 2.90 ± 0.97 mg/day, p < 0.001). Patients with *1/*3 genotype in CYP2C9 need doses lower than those with *1/*1 genotypes (1.73 ± 0.95 mg/day vs. 3.23 ± 1.13 mg/day, p < 0.001). There were no significant differences between the warfarin maintenance dosages in patients with atrial fibrillation (3.09 ± 1.16 mg/day), patients with heart valve replacement (2.95 ± 1.21 mg/day) and those with both atrial fibrillation and heart valve replacement (3.36 ± 1.13 mg/day) (p > 0.05). The mean warfarin daily dose requirements in the genotypes of VKORC1 and CYP2C9 were not dependent on the medical indication(s) present. CONCLUSIONS: Genetic variants of CYP2C9, VKORC1, and age are significant determinants of the maintenance dose of warfarin. The medical indications atrial fibrillation, valve replacement, or a combination of both are not determinants of the warfarin dose requirements.

Clinical characteristics and one year outcomes in Chinese atrial fibrillation patients with stable coronary artery disease: a population-based study.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) often coexist, however, the clinical characteristics and the impact of stable CAD on the outcomes in Chinese patients with AF has not been well understood. METHODS: Consecutive AF patients in 20 hospitals in China from November 2008 to October 2011 were enrolled. The primary endpoints included 1-year all-cause mortality, stroke, non-central nervous system (non-CNS) embolism, and major bleeding. RESULTS: A total of 1947 AF patients were analyzed, of whom 40.5% had stable CAD. The mean CHADS2 scores in CAD patients were significantly higher than that of non-CAD patients (2.4 ± 1.4 vs. 1.4 ± 1.2, P < 0.001). During follow-up period, warfarin use is low in both groups, with relatively higher proportion in non-CAD patients compared with CAD patients (22.3% vs. 10.7%, P < 0.001). Compared with non-CAD patients, CAD patients had higher one-year all-cause mortality (16.8% vs. 12.9%, P = 0.017) and incidence of stroke (9.0% vs. 6.4%, P = 0.030), while the non-CNS embolism and major bleeding rates were comparable between the two groups. After multivariate adjustment, stable CAD was independently associated with increased risk of 1-year all-cause mortality (HR = 1.35, 95% CI: 1.01-1 .80, P = 0.040), but not associated with stroke (HR = 1.07, 95% CI: 0.72-1.58, P = 0.736). CONCLUSIONS: Stable CAD was prevalent in Chinese AF patients and was independently associated with increased risk of 1-year all-cause mortality. Chinese AF patients with stable CAD received inadequate antithrombotic therapy and this grim status of antithrombotic therapy needed to be improved urgently.

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ±â€Š5.95 vs -1.82 ±â€Š4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

Comparison of 4 Admission Blood Pressure Indexes for Predicting 30-Day Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock. METHODS: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald χ (2) tests were used to compare the strength of relationships. RESULTS: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all-cause mortality; these in the highest vs. lowest quartiles of SBP (≥140 vs. <110mm Hg) and PP (≥60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (χ (2) = 5.9 for per 10mm Hg, χ (2) = 10.8 for quartiles) or women (χ (2) = 15.1 for per 10mm Hg, χ (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years. CONCLUSIONS: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign.

Serum Potassium Levels and Short-Term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction.

Current guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L (1 mEq/L = mmol/L) in patients with acute myocardial infarction. However, these guidelines are based on studies conducted before the ß blocker and reperfusion era. We retrospectively analyzed 6613 patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who presented without renal insufficiency. Patients were categorized into 5 groups according to mean serum potassium levels: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/L. Patients with potassium levels of 4.0 to <4.5 mEq/L had the lowest predefined event rates, which were 6.4% for 7-day malignant arrhythmia, 3.7% for 7-day mortality, and 5.3% for 30-day mortality. Compared with the reference group (4.0 to <4.5 mEq/L), multivariate regression analysis revealed significantly higher 30-day mortality risk in patients with potassium level of 4.5 to <5.0 (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.17-1.98; P = .002) and even higher risk in patients with potassium level of ≥5.0 mEq/L (HR: 1.80, 95% CI: 1.22-2.66; P = .002). The lowest 30-day mortality was observed in patients with STEMI having potassium levels between 4.0 and 4.5 mEq/L, and a level >4.5 mEq/L significantly increased mortality risk.

Impact of Admission Systolic Blood Pressure and Antecedent Hypertension on Short-Term Outcomes After ST-Segment Elevation Myocardial Infarction: Strobe-Compliant Article.

We evaluated the combined effect of admission systolic blood pressure (SBP) and antecedent hypertension on short-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Data were derived from a multicenter survey of 7303 consecutive patients with STEMI. Patients were divided into 4 groups according to different blood pressure status: high SBP without hypertension, high SBP with hypertension, low SBP without hypertension, and low SBP with hypertension. The primary endpoints were 7 and 30-day all-cause mortality. The prevalence of hypertension was 40.7%, and the best cutoff of admission SBP for predicting 30-day mortality was 108 mmHg by receiver-operating characteristic curve. Patients with hypertension were older, more often female, also had longer onset-to-admission time, more comorbidities, and higher Killip class. Patients with both low SBP (≤108 mmHg) and hypertension group had significantly higher 7 and 30-day mortality than those in other groups (all P < 0.001). After multivariate adjustment, low SBP with hypertension group was still an independent risk factor for predicting 7-day mortality (hazard ratios [HR] 1.86, 95% confidence interval [CI] 1.41-2.46; P < 0.001) and 30-day mortality (HR 1.88, 95% CI 1.46-2.43; P < 0.001). In patients with SBP > 108 mmHg, a history of hypertension could increase the risk of 30-day mortality by 27% (HR 1.00 vs 1.27, P = 0.012), while in patients with SBP ≤ 108 mmHg, this increased risk reached to 37% (HR 1.51 vs 1.88, P < 0.001). In conclusion, low admission SBP was the relatively dominant contributor for predicting 7 and 30-day all-cause mortality, and a concurrent antecedent hypertension increased the corresponding risk of mortality.

Association of Admission Glycaemia With High Grade Atrioventricular Block in ST-Segment Elevation Myocardial Infarction Undergoing Reperfusion Therapy: An Observational Study.

Several studies have demonstrated the association between elevated admission glycaemia (AG) and the occurrence of some arrhythmias such as atrial fibrillation, ventricular tachycardia, and ventricular fibrillation after myocardial infarction. However, the impact of elevated AG on the high grade atrioventricular block (AVB) occurrence after ST-segment elevation myocardial infarction (STEMI) remains unclear. Included were 3359 consecutive patients with STEMI who received reperfusion therapy. The primary endpoint was the development of high grade AVB during hospital course. Patients were divided into non-diabetes mellitus (DM), newly diagnosed DM, and previously known DM according to the hemoglobin A1c level. The optimal AG value was determined by receiver operating characteristic curves analysis with AG predicting the high grade AVB occurrence. The best cut-off value of AG for predicting the high grade AVB occurrence was 10.05 mmol/L by ROC curve analysis. The prevalence of AG ≥ 10.05 mmol/L in non-DM, newly diagnosed DM, and previously known DM was 15.7%, 34.1%, and 68.5%, respectively. The incidence of high grade AVB was significantly higher in patients with AG ≥ 10.05  mmol/L than <10.05  mmol/L in non-DM (5.7% vs. 2.1%, P < 0.001) and in newly diagnosed DM (10.2% vs.1.4%, P < 0.001), but was comparable in previously known DM (3.6% vs. 0.0%, P = 0.062). After multivariate adjustment, AG ≥ 10.05  mmol/L was independently associated with increased risk of high grade AVB occurrence in non-DM (HR = 1.826, 95% CI 1.073-3.107, P = 0.027) and in newly diagnosed DM (HR = 5.252, 95% CI 1.890-14.597, P = 0.001). Moreover, both AG ≥ 10.05  mmol/L and high grade AVB were independent risk factors of 30-day all cause-mortality (HR = 1.362, 95% CI 1.006-1.844, P = 0.046 and HR = 2.122, 95% CI 1.154-3.903, P = 0.015, respectively). Our study suggested that elevated AG level (≥10.05  mmol/L) might be an indicator of increased risk of high grade AVB occurrence in patients with STEMI.