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.

Treatment of Primary Aldosteronism and Reversal of Renin Suppression Improves Left Ventricular Systolic Function.

Introduction: Primary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA. Methods: We prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment. Results: At baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by -2.3, 95% CI: -3.9 to -0.6, P = 0.010, and post-medications by -1.3, 95% CI: -2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e' (P = 0.006), whereas it was not statistically significant in patients treated with medications. Conclusion: Treatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03174847.

Improvement in quality of life and psychological symptoms after treatment for primary aldosteronism: Asian Cohort Study.

BACKGROUND: In addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related quality of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy. METHODS: Thirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment. RESULTS: At 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treatment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improvement in the affective domain of BDI-II at 1 year post-treatment. CONCLUSION: Both surgical and medical therapy improve HRQoL and psychological symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.

A Vital Signs Telemonitoring Programme Improves the Dynamic Prediction of Readmission Risk in Patients with Heart Failure.

Heart failure (HF) is a leading cause of hospital readmissions. There is great interest in approaches to efficiently predict emerging HF-readmissions in the community setting. We investigate the possibility of leveraging streaming telemonitored vital signs data alongside readily accessible patient profile information for predicting evolving 30-day HF-related readmission risk. We acquired data within a non-randomized controlled study that enrolled 150 HF patients over a 1-year post-discharge telemonitoring and telesupport programme. Using the sequential data and associated ground truth readmission outcomes, we developed a recurrent neural network model for dynamic risk prediction. The model detects emerging readmissions with sensitivity > 71%, specificity > 75%, AUROC ~80%. We characterize model performance in relation to telesupport based nurse assessments, and demonstrate strong sensitivity improvements. Our approach enables early stratification of high-risk patients and could enable adaptive targeting of care resources for managing patients with the most urgent needs at any given time.

Nitrates in combination with hydralazine in cardiorenal syndrome: a randomized controlled proof-of-concept study.

AIMS: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine-isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. METHODS AND RESULTS: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 ]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481-2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2 ) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, -12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. CONCLUSIONS: Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.

Effectiveness of telemonitoring-enhanced support over structured telephone support in reducing heart failure-related healthcare utilization in a multi-ethnic Asian setting.

AIMS: Our study aimed to compare the effectiveness of telemonitoring over structured telephone support in reducing heart failure-related healthcare utilization. METHODS: This was a non-randomised controlled study comparing 150 recently discharged heart failure patients enrolled into telemonitoring and 55 patients who only received structured telephone support after rejecting telemonitoring. Patient activation, knowledge and self-management levels were measured at baseline and the one year upon programme completion using the Patient Activation Measure, the Dutch Heart Failure Knowledge Scale and the Self-Care of Heart Failure Index respectively. Differences in heart failure-related and all-cause hospitalization rates, total bed days and mortality rates at 180 days and at one year, knowledge and self-management scores and total cost of care between groups at one year were analysed. RESULTS: Average age of telemonitoring was 57.9 years and 63.9 years for structured telephone support. Significant difference in adjusted 180-day all-cause bed days (telemonitoring: five days versus structured telephone support: 9.8 days), heart failure-related bed days (telemonitoring: 1.2 days versus structured telephone support: six days) and adjusted one-year heart failure-related bed days (telemonitoring: 2.2 days versus structured telephone support: 6.6 days) were observed. Telemonitoring was associated with reduced all-cause one-year mortality (hazard ratio 0.32, p = 0.02). Estimated mean maintenance and confidence scores were significantly higher in the telemonitoring group at one year. No differences in all-cause and HF-related readmission rates and knowledge levels were observed. The one-year total cost of care was predicted to be Singapore dollars (SG$) 2774.4 lower (p = 0.07) in telemonitoring. CONCLUSION: In conclusion, telemonitoring was associated with lower all-cause and heart failure-related total bed days at 180 days, lower heart failure-related total bed days and total cost of care at one year as compared with structured telephone support.

Accuracy and clinical outcomes of coronary CT angiography for patients with suspected coronary artery disease: a single-centre study in Singapore.

INTRODUCTION: This study aimed to assess the accuracy and outcomes of coronary computed tomography angiography (CCTA) performed in a regional hospital in Singapore. METHODS: The Changi General Hospital CCTA database was retrospectively analysed over a 24-month period. Electronic hospital records, catheter coronary angiography (CCA) and CCTA electronic databases were used to gather data on major adverse cardiovascular events (MACE) and CCA results. CCTA findings were deemed positive if coronary artery stenosis ≥ 50% was reported or if the stenosis was classified as moderate or severe. CCA findings were considered positive if coronary artery stenosis ≥ 50% was reported. RESULTS: The database query returned 679 patients who had undergone CCTA for the evaluation of suspected coronary artery disease. Of the 101 patients in the per-patient accuracy analysis group, there were six true negatives, one false negative, 81 true positives and 13 false positives, resulting in a negative predictive value of 85.7% and positive predictive value of 86.2%. The mean age of the study sample was 53 ± 13 years and 255 (37.6%) patients were female. Mean duration of patient follow-up was 360 days. Of the 513 negative CCTA patients, none developed MACE during the follow-up period, and of the 164 positive CCTA patients, 19 (11.6%) developed MACE (p < 0.001). CONCLUSION: Analysis of CCTA studies suggested accuracy and outcomes that were consistent with published clinical data. There was a one-year MACE-free warranty period following negative CCTA findings.

Effects of carbon dioxide on juveniles of the freshwater mussel (Lampsilis siliquoidea [Unionidae]).

Carbon dioxide (CO2 ) has shown promise as a tool to control movements of invasive Asian carp, but its effects on native freshwater biota have not been well studied. The authors evaluated lethal and sublethal responses of juvenile fatmucket (Lampsilis siliquoidea) mussels to CO2 at levels (43-269 mg/L, mean concentration) that bracket concentrations effective for deterring carp movement. The 28-d lethal concentration to 50% of the mussels was 87.0 mg/L (95% confidence interval [CI] 78.4-95.9) and at 16-d postexposure, 76.0 mg/L (95% CI 62.9-90.3). A proportional hazards regression model predicted that juveniles could not survive CO2 concentrations >160 mg/L for more than 2 wk or >100 mg/L CO2 for more than 30 d. Mean shell growth was significantly lower for mussels that survived CO2 treatments. Growth during the postexposure period did not differ among treatments, indicating recovery of the mussels. Also, CO2 caused shell pitting and erosion. Behavioral effects of CO2 included movement of mussels to the substrate surface and narcotization at the highest concentrations. Mussels in the 110 mg/L mean CO2 treatment had the most movements in the first 3 d of exposure. If CO2 is infused continuously as a fish deterrent, concentrations <76 mg/L are recommended to prevent juvenile mussel mortality and shell damage. Mussels may survive and recover from brief exposure to higher concentrations. Environ Toxicol Chem 2017;36:671-681. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Risk Stratification Model for 30-Day Heart Failure Readmission in a Multiethnic South East Asian Community.

There are limited accurate 30-day heart failure (HF) readmission risk scores using readily available clinical patient information on a well-defined HF cohort. We analyzed 1,475 admissions discharged from our hospital with a primary diagnosis of HF between 2010 and 2012. HF diagnostic criteria included satisfying clinical Framingham criteria, elevated serum N-terminal pro-natriuretic peptide, and evidence of cardiac dysfunction on transthoracic echocardiography. The patients were randomly divided into 2 groups; 60% were used as the derivation cohort and 40% as the validation cohort. Bivariate analysis and logistic regression were used to develop the model. Weighted risk scores were derived from the odds ratio of the logistic regression model. Total risk scores were computed by simple summation for each patient. The 7 significant independent predictors of 30-day HF readmission used to derive the risk scoring tool were the number of previous HF-related admission in the preceding 1 year, index admission length of stay, serum creatinine level, electrocardiograph QRS duration, serum N-terminal pro-natriuretic peptide level, number of Medical Social Service needs, and ß blocker prescription on discharge. The area under the curve was 0.76. Sensitivity and specificity were 78.3% and 60.7%, respectively. The positive predictive value and negative predictive value were 18.9% and 96%, respectively. The actual observed and predicted 30-day heart failure readmission rates matched. In conclusion, we have developed the first 30-day HF readmission risk score, with good discriminatory ability, for an urban multiethnic Asian heart failure cohort with stringent diagnostic criteria. It consists of 7 easily obtained variables.

Non-fluoroscopic navigation systems for radiofrequency catheter ablation for supraventricular tachycardia reduce ionising radiation exposure.

INTRODUCTION: The use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time. METHODS: We prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO® mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported. RESULTS: A total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 ± 11.1 minutes vs. 32.0 ± 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 ± 5,768 mGy*cm2 vs. CF: 21,070 ± 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups. CONCLUSION: The use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time.

Comparison of Characteristics and Outcomes of Heart Failure Patients With Preserved Versus Reduced Ejection Fraction in a Multiethnic Southeast Asian Cohort.

There are few data comparing the patient characteristics and outcomes of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) in Asian cohorts. We aimed to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian HFpEF cohort in comparison to an HFrEF cohort. We conducted a retrospective observational study of 1,978 patients discharged from Changi General Hospital, Singapore with a primary diagnosis of HF from 2009 to 2013. About 29% of discharges had HFpEF. Patients with HFpEF were more likely to be women, older age, and have a higher prevalence of hypertension. There were no significant differences in the absolute rates of 30-day outcomes between the 2 groups. The absolute rate of death at 1 year was similar in HFrEF and HFpEF at 17% and 15%, respectively (p = 0.3). After multivariate adjustment, there was no difference in the outcomes of the 2 groups. Atrial fibrillation at baseline was a predictor of death or HF hospitalization in HFpEF but not HFrEF (interaction p = 0.003). In conclusion, in this study of a Southeast Asian population with well-defined HF, we found that the clinical profile of patients with HF was similar to that in the West and 30-day and 1-year mortality and morbidity were not significantly different between cohorts.