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.

Financial difficulties and patient-reported outcomes among patients with advanced heart failure.

PURPOSE: Management of congestive heart failure (CHF) is associated with high health care costs and financial difficulties for patients. We aimed to comprehensively assess the association between financial difficulties and patients' quality of life (QOL) (physical, emotional, social and spiritual), perceived health care quality, and perception of being a burden to the family among patients with CHF; and to assess whether perceived control over stress moderated these associations. METHODS: This was a cross-sectional study of 250 patients using the baseline data of the Singapore Cohort of Patients with Advanced Heart Failure (SCOPAH). Patients had class 3 or 4 CHF symptoms based on the New York Heart Association and were recruited between July 2017 and August 2019. We used a 3-item questionnaire to measure financial difficulties among patients. We used multivariable linear/ordered logistic regressions to test associations between financial difficulties and each dependent variable. RESULTS: 41% of participants reported financial difficulties. A higher financial difficulties score (range: 0-6, higher score indicating greater difficulty) was associated with lower QOL (emotional, social, and spiritual) and perceived health care coordination, and a higher likelihood of patients perceiving themselves to being a burden to family (all p < 0.05) CONCLUSION: Patients with financial difficulties are vulnerable to poor outcomes. Heart failure clinics should directly assess patients' financial difficulties to help guide treatment-related discussions and to identify patients vulnerable to poor QOL.

Instability in Preference for Place of Death Among Patients With Symptoms of Advanced Heart Failure.

OBJECTIVES: Patient preference for place of death is an important component of advance care planning (ACP). If patients' preference for place of death changes over time, this questions the value of their documented preference. We aimed to assess the extent and correlates of change in preference for place of death over time among patients with symptoms of advanced heart failure. DESIGN: We conducted a secondary analysis of data from a randomized controlled trial of a formal ACP program vs usual care. SETTING AND PARTICIPANTS: We interviewed 282 patients aged 21 years old and above with heart failure and New York Heart Association Classification III and IV symptoms in Singapore. Analytic sample included 200 patients interviewed at least twice. METHODS: We assessed factors associated with patients' preference for place of death (home/institution/no preference) and change in their preference for place of death from previous time point (change toward home death/toward an institutional death/toward no preference/no change). These included patient demographics, quality of life (Kansas City Cardiomyopathy Questionnaire), and prognostic understanding. RESULTS: In our study, 66% of patients with heart failure changed their preference for place of death at least once during the study period with no consistent pattern of change. Correct prognostic understanding at the time of survey reduced the relative risk of change in preference for place of death to home (relative risk ratio 0.49, 95% confidence interval 0.32, 0.76), whereas a higher quality of life score was associated with a lower relative risk of patients changing their preferred place of death to an institution (relative risk ratio 0.99, 95% confidence interval 0.97, 1.00) relative to no change in preference. CONCLUSIONS AND IMPLICATIONS: We provide evidence of instability in patients with heart failure preference for place of death, which suggests that ACP documents should be regularly re-evaluated.

Instability in End-of-Life Care Preference Among Heart Failure Patients: Secondary Analysis of a Randomized Controlled Trial in Singapore.

BACKGROUND: Efforts to improve quality of end-of-life (EOL) care are increasingly focused on eliciting patients' EOL preference through advance care planning (ACP). However, if patients' EOL preference changes over time and their ACP documents are not updated, these documents may no longer be valid at the time EOL decisions are made. OBJECTIVES: To assess extent and correlates of changes in stated preference for aggressive EOL care over time. DESIGN: Secondary analysis of data from a randomized controlled trial of a formal ACP program versus usual care in Singapore. PATIENTS: Two hundred eighty-two patients with heart failure (HF) and New York Heart Association Classification III and IV symptoms were recruited and interviewed every 4 months for up to 2 years to assess their preference for EOL care. Analytic sample included 200 patients interviewed at least twice. RESULTS: Nearly two thirds (64%) of patients changed their preferred type of EOL care at least once. Proportion of patients changing their stated preference for type of EOL care increased with time and the change was not unidirectional. Patients who understood their prognosis correctly were less likely to change their preference from non-aggressive to aggressive EOL care (OR 0.66, p value 0.07) or to prefer aggressive EOL care (OR 0.53; p value 0.001). On the other hand, patient-surrogate discussion of care preference was associated with a higher likelihood of change in patient preference from aggressive to non-aggressive EOL care (OR 1.83; p value 0.03). CONCLUSION: The study provides evidence of instability in HF patients' stated EOL care preference. This undermines the value of an ACP document recorded months before EOL decisions are made unless a strategy exists for easily updating this preference. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02299180.

Impact of a Formal Advance Care Planning Program on End-of-Life Care for Patients With Heart Failure: Results From a Randomized Controlled Trial.

BACKGROUND: There is no evidence on effectiveness of advance care planning (ACP) among patients with heart failure (HF). We examined the effect of an ACP program in facilitating end of life (EOL) care consistent with the preferences of patients with HF (primary aim), and on their decisional conflict, discussion with surrogates, illness understanding, anxiety, depression, and quality of life (secondary aims). METHODS: We randomized 282 patients with HF to receive ACP (n=93) or usual care (control arm, n=189). Primary outcomes were assessed among deceased (n=89) and secondary outcomes from baseline and 6 follow-ups conducted every 4 months. RESULTS: Deceased patients in the ACP arm were no more likely than those in control arm to have wishes followed for EOL treatments (ACP: 35%, Control: 44%; P= .47), or place of death (ACP: 52%, Control: 51%; P = .1.00). A higher proportion in the ACP arm had wishes followed for cardiopulmonary resuscitation (ACP: 83%, Control: 62%; P = .12). At first follow-up, patients with ACP had lower decisional conflict (ß = -10.8, P< .01) and were more likely to discuss preferences with surrogates (ß = 1.3, P = .04). ACP did not influence other outcomes. CONCLUSION: This trial did not confirm that our ACP program was effective in facilitating EOL care consistent with patient preferences. The program led to short-term improvements in the decision-making.

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.

More than meets the eye: Varicella zoster virus-related orbital apex syndrome.

A 67-year-old male patient with poorly controlled type-2 diabetes mellitus developed an orbital apex syndrome and anterior cavernous syndrome secondary to herpetic zoster ophthalmicus (HZO), despite being on oral acyclovir. Urgent treatment with intravenous acyclovir led to improvement of the orbital and ocular inflammation but had no effect on the complete ophthalmoplegia and profound visual loss. At the 9-month follow-up visit, the patient had complete unilateral ophthalmoplegia and monocular blindness due to optic atrophy.

Influenza-Associated Hospitalizations for Cardiovascular Diseases in the Tropics.

Influenza is a major cause of mortality and morbidity. We aimed to examine the influenza-associated hospitalization rates and proportions for cardiovascular disease (CVD) in tropical Singapore. Hospital admissions for ischemic heart disease (IHD), congestive heart failure (CHF), and overall CVD were obtained from the national inpatient database for the period of 2010-2014. We used, as the key indicator of influenza virus activity, the overall proportion of specimens from outpatients with influenza-like illness in the community that tested positive for influenza as part of the national influenza surveillance program. The annual influenza-associated hospitalization rates per 100,000 person-years ranged from 9.5 to 12.2 for IHD, 7.7 to 9.1 for CHF, and 15.8 to 19.2 for overall CVD. The influenza-associated hospitalization rates increased with increasing age. Influenza was significantly associated with excess hospitalizations in elderly persons aged ≥80 years, with an excess hospitalization rate per 100,000 person-years of 242.7 for IHD (P = 0.02), 271.8 for CHF (P = 0.01), and 497.2 for overall CVD (P < 0.001). In the tropics, influenza accounts for excess cardiovascular-related hospitalizations, especially in the elderly.

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.