Long-term mortality after isolated coronary artery bypass grafting and risk factors for mortality.

BACKGROUND: Patients requiring coronary artery bypass grafting (CABG) have multiple co-morbidities which need to be considered in totality when determining surgical risks. The objective of this study is to evaluate short-term and long-term mortality rates of CABG surgery, as well as to identify the most significant risk factors for mortality after isolated CABG. METHODS: All patients with complete dataset who underwent isolated CABG between January 2008 and December 2017 were included. Univariate and multivariate Cox regression was performed to determine the risk factors for all-cause mortality. Classification and regression tree analysis was performed to identify the relative importance of these risk factors. RESULTS: 3,573 patients were included in the study. Overall mortality rate was 25.7%. In-hospital mortality rate was 1.62% overall. 30-day, 1-year, 5-year, 10-year and 14.5-year mortality rates were 1.46%, 2.94%, 9.89%, 22.79% and 36.30% respectively. Factors associated with death after adjustment for other risk factors were older age, lower body mass index (BMI), hypertension, diabetes mellitus, chronic obstructive pulmonary disease, pre-operative renal failure on dialysis, higher last pre-operative creatinine level, lower estimated glomerular filtration rate (eGFR), heart failure, lower left ventricular ejection fraction and New York Heart Association class II, III and IV. Additionally, female gender and logistic EuroSCORE were associated with death on univariate Cox analysis, but not associated with death after adjustment with multivariate Cox analysis. Using CART analysis, the strongest predictor of mortality was pre-operative eGFR < 46.9, followed by logistic EuroSCORE ≥ 2.4. CONCLUSION: Poorer renal function, quantified by a lower eGFR, is the best predictor of post-CABG mortality. Amongst other risk factors, logistic EuroSCORE, age, diabetes and BMI had a relatively greater impact on mortality. Patients with chronic kidney disease stage 3B and above are at highest risk for mortality. We hope these findings heighten awareness to optimise current medical therapy in preserving renal function upon diagnosis of any atherosclerotic disease and risk factors contributing to coronary artery disease.

Clinical characteristics and outcomes in Asian patients with heart failure with mildly reduced ejection fraction.

Introduction: Data on heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is still emerging, especially in Asian populations. This study aims to compare the clinical characteristics and outcomes of Asian HFmrEF patients with those of HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods: Patients admitted nationally for HF between 2008 and 2014 were included in the study. They were categorised according to ejection fraction (EF). Patients with EF <40%, EF 40%-49% and EF ≥50% were categorised into the following groups: HFrEF, HFmrEF and HFpEF, respectively. All patients were followed up till December 2016. Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular death and/or HF rehospitalisations. Results: A total of 16,493 patients were included in the study - HFrEF, n = 7,341 (44.5%); HFmrEF, n = 2,272 (13.8%); and HFpEF n = 6,880 (41.7%). HFmrEF patients were more likely to be gender neutral, of mid-range age and have concomitant diabetes mellitus, hyperlipidaemia, peripheral vascular disease and coronary artery disease (P < 0.001). The two-year overall mortality rates for HFrEF, HFmrEF and HFpEF were 32.9%, 31.8% and 29.1%, respectively. HFmrEF patients had a significantly lower overall mortality rate compared to HFrEF patients (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.83-0.95; P < 0.001) and a significantly higher overall mortality rate (adjusted HR 1.25, 95% CI 1.17-1.33; P < 0.001) compared to HFpEF patients. This was similarly seen with cardiovascular mortality and HF hospitalisations, with the exception of similar HF hospitalisations between HFmrEF and HFpEF patients. Conclusion: HFmrEF patients account for a significant burden of patients with HF. HFmrEF represents a distinct HF phenotype with high atherosclerotic burden and clinical outcomes saddled in between those of HFrEF and HFpEF. Further therapeutic studies to guide management of this challenging group of patients are warranted.

Interaction of sex and diabetes in Asian patients with heart failure with mildly reduced left ventricular ejection fraction.

INTRODUCTION: The impact of sex and diabetes mellitus (DM) on patients with heart failure with mildly reduced ejection fraction (HFmrEF) is not well elucidated. This study aims to evaluate sex differences in the clinical profile and outcomes in Asian HFmrEF patients with and without DM. METHODS: Patients admitted nationally for HFmrEF (ejection fraction 40-49%) between 2008 and 2014 were included and followed up until December 2016. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular (CV) death and/or heart failure (HF) rehospitalisations. RESULTS: A total of 2,272 HFmrEF patients (56% male) were included. More women had DM than men (60% versus 55%, P=0.013). Regardless of DM status, HFmrEF females were older, less likely to smoke, had less coronary artery disease, narrower QRS and lower haemoglobin compared to men. The odds of having DM decreases in smokers who are women as opposed to men (Pinteraction =0.017). In multivariate analysis, DM reached statistical analysis for all-cause mortality and combined CV mortality or HF rehospitalisation in both men and women. However, the results suggest that there may be sex differences in terms of outcomes. DM (vs non-DM) was less strongly associated with increased all-cause mortality (adjusted hazards ratio [adj HR] 1.234 vs adj HR 1.290, Pinteraction <0.001] but more strongly associated with the combined CV death/HF rehospitalisation (adj HR 1.429 vs adj HR 1.317, Pinteraction =0.027) in women (vs men). CONCLUSION: Asian women with HFmrEF had a higher prevalence of DM, with differences in clinical characteristics, compared to men. While diabetes conferred poor outcomes regardless of sex, there were distinct sex differences. These highlight the need for sex-specific management strategies.

Predicting Coronary Artery Disease in Primary Care: Development and Validation of a Diagnostic Risk Score for Major Ethnic Groups in Southeast Asia.

BACKGROUND: Coronary artery disease (CAD) risk prediction tools are useful decision supports. Their clinical impact has not been evaluated amongst Asians in primary care. OBJECTIVE: We aimed to develop and validate a diagnostic prediction model for CAD in Southeast Asians by comparing it against three existing tools. DESIGN: We prospectively recruited patients presenting to primary care for chest pain between July 2013 and December 2016. CAD was diagnosed at tertiary institution and adjudicated. A logistic regression model was built, with validation by resampling. We validated the Duke Clinical Score (DCS), CAD Consortium Score (CCS), and Marburg Heart Score (MHS). MAIN MEASURES: Discrimination and calibration quantify model performance, while net reclassification improvement and net benefit provide clinical insights. KEY RESULTS: CAD prevalence was 9.5% (158 of 1658 patients). Our model included age, gender, type 2 diabetes mellitus, hypertension, smoking, chest pain type, neck radiation, Q waves, and ST-T changes. The C-statistic was 0.808 (95% CI 0.776-0.840) and 0.815 (95% CI 0.782-0.847), for model without and with ECG respectively. C-statistics for DCS, CCS-basic, CCS-clinical, and MHS were 0.795 (95% CI 0.759-0.831), 0.756 (95% CI 0.717-0.794), 0.787 (95% CI 0.752-0.823), and 0.661 (95% CI 0.621-0.701). Our model (with ECG) correctly reclassified 100% of patients when compared with DCS and CCS-clinical respectively. At 5% threshold probability, the net benefit for our model (with ECG) was 0.063. The net benefit for DCS, CCS-basic, and CCS-clinical was 0.056, 0.060, and 0.065. CONCLUSIONS: PRECISE (Predictive Risk scorE for CAD In Southeast Asians with chEst pain) performs well and demonstrates utility as a clinical decision support for diagnosing CAD among Southeast Asians.

Impact of Chronic Kidney Disease on Outcomes in Transcatheter Aortic Valve Implantation.

INTRODUCTION: Chronic kidney disease (CKD) is a significant comorbidity in aortic stenosis (AS) patients. We examined the impact of baseline CKD, postoperative acute kidney injury (AKI) and CKD progression on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI). MATERIALS AND METHODS: Consecutive patients with severe AS who underwent TAVI were classified into CKD stages 1-2 (≥60 mL/min/1.72m2), 3 (30-59 mL/min/1.73m2) and 4-5 (<30 mL/min/1.73m2 or dialysis) based on estimated glomerular filtration rate (eGFR). Primary outcome was mortality and secondary outcomes included 1-year echocardiographic data on aortic valve area (AVA), mean pressure gradient (MPG) and aortic regurgitation (AR). RESULTS: A total of 216 patients were included. Higher eGFR was associated with lower overall mortality (adjusted hazards ratio [AHR] 0.981, 95% confidence interval [CI] 0.968-0.993, P = 0.002). CKD 4-5 were associated with significantly higher mortality from non-cardiovascular causes (P <0.05). Patients with CKD 3-5 had higher incidence of moderate AR than those with CKD 1-2 (P = 0.010); no difference in AVA and MPG was seen. AKI patients had higher mortality (P = 0.008), but the effect was attenuated on multivariate analysis (AHR 1.823, 95% CI 0.977-3.403, P = 0.059). Patients with CKD progression also had significantly higher mortality (AHR 2.969, 95% CI 1.373-6.420, P = 0.006). CONCLUSION: CKD in severe AS patients undergoing TAVI portends significantly higher mortality and morbidity. Renal disease progression impacts negatively on outcomes and identifies a challenging subgroup of patients for optimal management.

The Singapore Heart Failure Risk Score: Prediction of Survival in Southeast Asian Patients.

INTRODUCTION: Numerous heart failure risk scores have been developed but there is none for Asians. We aimed to develop a risk calculator, the Singapore Heart Failure Risk Score, to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure. MATERIALS AND METHODS: Consecutive patients admitted for heart failure were identified from the Singapore Cardiac Databank Heart Failure registry. The follow-up was 2 to 4 years and mortality was obtained from national registries. RESULTS: The derivation (2008-2009) and 2 validation cohorts (2008-2009, 2013) included 1392, 729 and 804 patients, respectively. Ten variables were ultimately included in the risk model: age, prior myocardial infarction, prior stroke, atrial fibrillation, peripheral vascular disease, systolic blood pressure, QRS duration, ejection fraction and creatinine and sodium levels. In the derivation cohort, predicted 1- and 2-year survival was 79.1% and 68.1% compared to actual 1- and 2-year survival of 78.2% and 67.9%. There was good agreement between the predicted and observed mortality rates (Hosmer-Lemeshow statistic = 14.36, P = 0.073). C-statistics for 2-year mortality in the derivation and validation cohorts were 0.73 (95% CI, 0.70-0.75) and 0.68 (95% CI, 0.64-0.72), respectively. CONCLUSION: We provided a risk score based on readily available clinical characteristics to predict 1- and 2-year survival in Southeast Asian patients hospitalised for heart failure via a simple online risk calculator, the Singapore Heart Failure Risk Score.

Prediction of Survival in Asian Patients Hospitalized With Heart Failure: Validation of the OPTIMIZE-HF Risk Score.

BACKGROUND: Risk scores predicting in-patient mortality in heart failure patients have not been designed specifically for Asian patients. We aimed to validate and recalibrate the OPTIMIZE-HF risk model for in-hospital mortality in a multiethnic Asian population hospitalized for heart failure. METHODS AND RESULTS: Data from the Singapore Cardiac Databank Heart Failure on patients admitted for heart failure from January 1, 2008, to December 31, 2013, were included. The primary outcome studied was in-hospital mortality. Two models were compared: the original OPTIMIZE-HF risk model and a modified OPTIMIZE-HF risk model (similar variables but with coefficients derived from our cohort). A total of 15,219 patients were included. The overall in-hospital mortality was 1.88% (n = 286). The original model had a C-statistic of 0.739 (95% CI 0.708-0.770) with a good match between predicted and observed mortality rates (Hosmer-Lemeshow statistic 13.8; P = .086). The modified model had a C-statistic of 0.741 (95% CI 0.709-0.773) but a significant difference between predicted and observed mortality rates (Hosmer-Lemeshow statistic 17.2; P = .029). The modified model tended to underestimate risk at the extremes (lowest and highest ends) of risk. CONCLUSIONS: We provide the first independent validation of the OPTIMIZE-HF risk score in an Asian population. This risk model has been shown to perform reliably in our Asian cohort and will potentially provide clinicians with a useful tool to identify high-risk heart failure patients for more intensive management.

Mortality outcome and predictive risk factors for death in patients with heart failure and reduced ejection fraction who declined implantable cardioverter defibrillator implantation in Singapore.

BACKGROUND: There have been conflicting data regarding the risk of sudden cardiac death (SCD) in Asian population with reduced left ventricular ejection fraction (LVEF). We aim to study mortality outcome and its risk predictors in patients with reduced LVEF who declined an implantable cardioverter defibrillator (ICD) implantation and assess whether current ICD guidelines for primary prevention are applicable to the population in Singapore. METHODS: This prospective observational study involved 240 consecutive patients who fulfilled the ACC/AHA/HRS criteria for ICD implantation for primary prevention of SCD but declined ICD implantation. Baseline characteristics and mortality outcomes through May 2017 were collected via case-note review after a mean follow-up of 44.8 ± 16.6 months. RESULTS: Majority of our patients were Chinese (71.3%), followed by Malays (16.2%) and Indians (10.8%). Mean age (±SD) was 61 ± 10 years, and 84% were male. Majority were in New York Heart Association (NYHA) functional classes I (46.7%) and II (46.3%). Over a mean follow-up of 44.8 ± 16.6 months, all-cause mortality rate was 34.6%. Diabetes mellitus (HR = 1.57; 95% CI, 1.01-2.44; P = 0.047) and chronic kidney disease (CKD; HR = 1.95; 95% CI, 1.17-3.23; P = 0.010) were independent predictors of mortality. Patients in NYHA classes II (HR = 2.15; 95% CI, 1.32-3.50; P = 0.002) and III (HR = 2.82; 95% CI, 1.34-5.96; P = 0.007) showed higher risk of death. CONCLUSION: The mortality rate was comparable with major primary prevention trials. ICD guideline recommendations for primary prevention may thus be applicable to our local population. Patients with diabetes, CKD, and poorer NYHA status exhibited higher mortality rates.

Long-Term Prognostic Value of Appropriate Myocardial Perfusion Imaging.

Appropriate use criteria (AUC) for single-photon emission computed tomography myocardial perfusion images (SPECT-MPIs) were developed to address the growth of cardiac imaging studies. Long-term prognostic value of AUC in SPECT-MPI has not been tested in existing cohorts. We sought to determine the long-term prognostic value of MPI classified as appropriate. AUC was evaluated in a prospectively designed cohort of patients who underwent clinically indicated MPI. MPI studies were classified based on 2009 AUC for SPECT-MPI. Data regarding downstream coronary angiography (cath), revascularization and all-cause mortality, cardiac death, and nonfatal myocardial infarction (MI) were collected from national registries. Among n = 1,129 MPI scans that received an appropriate grading, 148 all-cause deaths, 109 MIs, 58 cardiac deaths, 152 caths, 113 revascularization procedures occurred over a mean follow-up period of 5.4 ± 1.2 years (0.9% cardiac death rate per year, 1.8% MI rate per year). Most of the scans were low-risk normal MPI scans (summed stress score ≤3; 74.1%). An abnormal scan was associated with higher rates of MI (19.5% vs 6.2%, hazard ratio 1.72, p = 0.017) and cardiac death (13.4% vs 2.3%, hazard ratio 2.12, p = 0.016). In conclusion, MPI scans classified as appropriate have long-term prognostic value, despite a high proportion of low-risk scans. This provides support for clinicians to consider the use of appropriate grading in addition to MPI scan results in patient management.

Predictors of two-year mortality in Asian patients with heart failure and preserved ejection fraction.

INTRODUCTION: Mortality in patients with heart failure and preserved ejection fraction (HFpEF) remains high. Data from Asia is lacking. We aim to study the impact of ethnicity and other predictors of mortality in patients admitted for HFpEF in a multi-ethnic Asian country. MATERIAL AND METHODS: Consecutive patients admitted to two local institutions with heart failure and ejection fraction ≥50% on transthoracic echocardiogram from Jan 2008 to Dec 2009 were included. All patients were followed-up for 2 years. Overall mortality was obtained from the national registry of deaths in our country. RESULTS: A total of 1960 patients with heart failure were included. 751 (38.3%) patients had HFpEF. Overall mortality at two years was 26.6% (n=200) compared to 37.1% (n=449) in patients with reduced ejection fraction (HR 0.618 (95% CI 0.508-0.753), p<0.001). Ethnicity did not predict mortality. On multivariable Cox regression analysis, significant predictors of two-year mortality in HFpEF patients were older age (HR 1.027 (1.011-1.044)), prior myocardial infarction (HR 1.577 (1.104-2.253)), prior stroke (HR 1.475 (1.055-2.061)), smoking (HR 1.467 (1.085-1.985)), higher creatinine levels (HR 1.002 (1.001-1.003)) and use of mineralocorticoid receptor antagonists (HR 1.884 (1.226-2.896)). Use of warfarin (HR 0.506 (0.304-0.842)) and statins (HR 0.585 (0.435-0.785)) were associated with significantly lower mortality. CONCLUSIONS: In our Asian population presenting with HFpEF, two-year mortality was 26.6%. Ethnicity did not predict mortality. Older age, prior myocardial infarction, prior stroke, smoking, and higher creatinine levels were found to be significant predictors of mortality.

Predictors of mortality in acute heart failure: interaction between diabetes and impaired left ventricular ejection fraction.

AIM: The aim of this study was to test the hypothesis that diabetes modifies the risk of mortality in acute heart failure patients, especially in patients with impaired LVEF, and that impaired LVEF in turn modifies the risk of mortality in diabetic patients. METHODS AND RESULTS: We studied 2121 patients with acute heart failure admitted at two centres in Singapore from 1 January 2008 to 31 December 2009. The date of the last follow-up was 31 December 2011, with a median follow-up time (interquartile range) of 914 (442-1190) days. Cox regression was used to estimate hazard ratios for all-cause mortality in patients with LVEF ≥50%, LVEF 30-49%, and LVEF <30% relative to diabetic status. Impaired LVEF (<50%) in the presence of diabetes substantially increased the risk of mortality compared with non-diabetics with LVEF <50%. The adjusted hazard ratio (aHR) and 95% confidence interval (CI) for diabetic patients with an LVEF of 30-49% (1.46, 95% 1.18-1.81) was not statistically different from the aHR in non-diabetic patients with severely impaired LVEF of <30% (1.38, 95% CI 1.09-1.75) (P = 0.644). The deleterious effects of diabetes seemed to be confined to acute heart failure patients with impaired LVEF, as the mortality rate in patients with LVEF >50% was not increased. Other clinical predictors of mortality were ageing, prior myocardial infarction, systolic blood pressure >140 mmHg, creatinine ≥250 µmol/L, haemoglobin <9.0 g/dL, and prior stroke/transient ischaemic attack. CONCLUSION: The interaction of diabetes and impaired LVEF in acute heart failure patients significantly amplifies the deleterious effects of each as distinct disease entities.

Impact Of Sex On Clinical Characteristics And In-Hospital Outcomes In A Multi-Ethnic Southeast Asian Population Of Patients Hospitalized For Acute Heart Failure.

OBJECTIVES: To study sex differences in clinical characteristics and outcomes among multi-ethnic Southeast Asian patients with hospitalized heart failure (HHF). BACKGROUND: HHF is an important public health problem affecting man and women globally. Reports from Western populations suggest striking sex differences in risk factors and outcomes in HHF. However, this has not been studied in a multi-ethnic Asian population. METHODS: Using the population-based resources of the Singapore Cardiac Data Bank, we studied 5,703 consecutive cases of HHF admitted across hospitals in the Southeast Asian nation of Singapore from 1st January, 2008 through 31st December, 2009. RESULTS: Women accounted for 46% of total admissions and were characterized by older age (73 vs. 67 years; p<0.001), higher prevalence of hypertension (78.6 vs. 72.1%; p<0.001) or atrial fibrillation (22.2 vs. 18.1%; p<0.001), and lower prevalence of coronary artery disease (33.8 vs. 41.0%; p<0.001) or prior myocardial infarction (14.9 vs. 19.8%; p<0.001). Women were more likely than men to have HHF with preserved ejection fraction (42.5% versus 20.8%, p < 0.001). Women were less likely than men to receive evidencebased therapies at discharge, both in the overall group and in the sub-group with reduced ejection fraction. Women had longer lengths of stay (5.6 vs. 5.1 days; p<0.001) but similar in-hospital mortality and one-year rehospitalization rates compared to men. Independent predictors of mortality or rehospitalization in both men and women included prior myocardial infarction and reduced ejection fraction. Among women alone, additional independent predictors were renal impairment, atrial fibrillation, and diabetes. Prescription of beta-blockers and ACE-inhibitors at discharge was associated with better outcomes. CONCLUSION: Among multi-ethnic Asian patients with HHF, there are important sex differences in clinical characteristics and prognostic factors. These data may inform sex-specific strategies to improve outcomes of HHF in Southeast Asians.