The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial.

BACKGROUND: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. METHODS: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. RESULTS: Patients were randomly assigned at a median of 4.4 [3.0-5.8] days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74-0.99], P=0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. CONCLUSIONS: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Associations Between Prognostic Awareness, Acceptance of Illness, and Psychological and Spiritual Well-being Among Patients With Heart Failure.

BACKGROUND: This study aimed to (1) investigate the association of prognostic awareness with psychological (distress level and emotional well-being) and spiritual well-being among patients with heart failure, and (2) assess the main and moderating effects of illness acceptance on the relationship between prognostic awareness and psychological and spiritual well-being. METHODS AND RESULTS: This study used baseline data of a Singapore cohort of patients with heart failure (N = 245) who had New York Heart Association class 3 or 4 symptoms. Patients reported their awareness of prognosis and extent of illness acceptance. Multivariable linear regressions were used to investigate the associations. Prognostic awareness was not significantly associated with psychological and spiritual well-being. Illness acceptance was associated with lower levels of distress (ß [SE] = -0.9 [0.2], P < .001), higher emotional well-being (ß [SE] = 2.2 [0.4], P < .001), and higher spiritual well-being (ß [SE] = 5.4 [0.7], P < .001). Illness acceptance did not moderate the associations of prognostic awareness with psychological and spiritual well-being. CONCLUSIONS: This study suggests that illness acceptance could be a key factor in improving patient well-being. Illness acceptance should be regularly assessed and interventions to enhance illness acceptance should be considered for those with poor acceptance.

Safety and Tolerability of Sacubitril/Valsartan Initiation in Inpatient Versus Outpatient Setting: A Retrospective Real World Study.

BACKGROUND: The Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION) and PIONEER-HF trialsa have shown that sacubitril/valsartan can be initiated early and safely in patients with heart failure with reduced ejection fraction (HFrEF) shortly after an acute heart failure episode during hospitalisation. However, it is unclear whether the results can be translated to Asian populations. Hence, this real-world study was designed with the aim of comparing the safety and tolerability of sacubitril/valsartan initiation in an inpatient versus outpatient setting. METHODS: A retrospective review for all patients initiated with sacubitril/valsartan from 1 November 2015 to 30 September 2018 was conducted in a tertiary health care institution in Singapore. Patients with HFrEF and aged ≥21 years were included. Incidence of adverse drug reactions (ADRs) and discontinuation rate of sacubitril/valsartan were compared between initiation of sacubitril/valsartan in inpatient and outpatient settings. Reasons for discontinuation were investigated. Subgroup analysis was performed. Cox regression was used to analyse the primary outcomes. RESULTS: Of the 1,022 patients who were screened, 840 (289 inpatient group; 551 outpatient group) were included. The inpatient group experienced significantly higher ADRs (34.6% vs 22.7%; adjusted hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.68-3.10; p<0.01) and discontinuation rate (18.0% vs 10.3%; adjusted HR, 2.11; 95% CI, 1.37-3.26; p<0.01) than the outpatient group. The safety outcomes were consistent across all the subgroups. CONCLUSIONS: Initiation of sacubitril/valsartan in an inpatient group was associated with higher ADRs and discontinuation rate as compared with an outpatient group in an Asian population. However, given that the majority of patients in the inpatient cohort could tolerate sacubitril/valsartan, it would still be feasible to initiate this drug with close monitoring. Further randomised clinical trials in Asian populations are required to confirm this finding.

Relationship between self-care adherence, time perspective, readiness to change and executive function in patients with heart failure.

This study examined the relationship between self-care adherence, time perspective (TP), readiness to change (RTC) and executive function in heart failure (HF) self-care. 147 heart failure patients completed questionnaires on self-care, TP, RTC; and cognitive tasks that reflect working memory and inhibition. Positive correlation was found between self-care, future-oriented TP (r = 0.362, P = 0.01), RTC (r = 0.184, P = 0.05) and working memory (r = 0.174, P = 0.01). Mediation analysis elucidated the indirect effect of RTC on self-care through TP (B = 1.205, bias-corrected bootstrapped at 95% confidence interval 0.532, 2.145) explaining 62.0% of the total effect. Working memory did not moderate this relationship and inhibition did not predict self-care. Self-care scores were lower than cut-off of 70 (mean = 51.2, standard deviation = 17.2). Age (r = - 0.220), staying alone (r = - 0.270) income < 1000 (r = - 0.270) and not having formal education (r = - 0.165) were correlated with TP. Healthcare professionals could motivate HF patients to perform regular self-care behaviours by tailoring interventions according to their TP and RTC.

Motivation, Challenges and Self-Regulation in Heart Failure Self-Care: a Theory-Driven Qualitative Study.

BACKGROUND: Self-care behaviours are crucial in reducing chronic heart failure (HF) morbidity and mortality but performance remains poor worldwide. This study draws on Temporal Self-regulation Theory (TST) to explore participants' motivations, challenges and personalised self-regulation strategies to enhance self-care. METHOD: Seventeen HF patients were purposively sampled and recruited from outpatient and inpatient settings at a Singaporean tertiary hospital from December 2017 to March 2018. Unstructured face-to-face interviews were conducted. Data were analysed using thematic analysis with constant comparison. RESULTS: Five themes emerged. Self-care motivations were (1) consideration of family's future and (2) consideration of own past, while demotivation was (3) fatalistic consideration of own future. Barriers of behaviour change were (4) difficulty adopting physical activity and (5) difficulty deviating from personal dietary habits and sociocultural dietary norms. Personalised strategies to overcome these challenges were described in the 12 subthemes that emerged. Themes were well-fitted into the TST-(1-3) corresponded to time perspective, (4-5) corresponds to behaviour prepotency and the subthemes corresponded to self-regulatory capacity. Motivation could be enhanced by stimulating considerations of one's past regrets, family's future well-being and real-life success stories to instil hope. Clinicians and case managers could enhance self-regulation by empowering patients with tactical and situational skills to develop personalised plans to improve lifestyle habits and strategies to resist temptations. CONCLUSION: Future person-centred self-care interventions could be tailored according to the study findings. Better self-care could improve patient outcomes, reduce rehospitalisation and alleviate global healthcare burden. Findings could be generalised to healthy populations as primary prevention.

Percutaneous Decommissioning of Left Ventricular Assist Device.

BACKGROUND: The left ventricular assist device (LVAD) has revolutionised our treatment of advanced stage heart failure, giving debilitated patients a new lease on life. A small proportion of these LVAD patients can be bridged-to-recovery. The identification of these patients and decision to wean, however, can be challenging. METHODS: The need to fully explant the device upon recovery has evolved to a minimalist approach aiming to avoid injury to the 'recovered' heart. A review of the evolution of explant strategies was performed to guide our decision to wean the LVAD in our early experience. RESULTS: Between 2009 and 2014, two patients in our series of 69 LVAD implants (2.9%) were successfully weaned off their LVADs. The second patient had a minimal access implantation of his HeartWare Ventricular Assist Device (HVAD, Medtronic Inc, Framingham, MA, USA). His clinical variables and minimalist weaning strategy are described. CONCLUSIONS: A case of LVAD decommissioning by thrombosis of the outflow graft, using percutaneous Amplatzer Vascular Plug II (St. Jude Medical, St. Paul, MN, USA) without surgery is reported.

Multifactorial risk factors for hospital readmissions among patients with symptoms of advanced heart failure.

AIMS: Economic burden of heart failure is attributed to hospital readmissions. Previous studies assessing risk factors for readmissions have focused on single group of risk factors, were limited to 30-day readmissions, or did not account for competing risk of mortality. This study investigates the biological, socio-economic, and behavioural risk factors predicting hospital readmissions while accounting for the competing risk of mortality. METHODS AND RESULTS: In this prospective cohort study, we recruited 250 patients hospitalized with symptoms of advanced heart failure [New York Heart Association (NYHA) Class III and IV] between July 2017 and April 2019. We analysed their baseline survey data and their hospitalization records over the next 4.5 years (July 2017 to January 2022). We used a joint-frailty model to determine the multifactorial risk factors for all-cause and unplanned hospital readmissions and mortality. At the time of recruitment, patients' mean (SD) age was 66 (12) years, majority being male (72%) and NYHA class IV (68%) with reduced ejection fraction (72%). 87% of the patients had poor self-care behaviours, 51% had diabetes and 56% had weak grip strength. Within 2 years of a hospital admission, 74% of the patients had at least one readmission. Among all readmissions during follow-up, 68% were unplanned. Results from the multivariable regression analysis shows that the independent risk factors for hospital readmissions were biologic-weak grip strength [hazard ratio (95% CI): 1.59 (1.06, 2.13)], poor functional status [1.79 (0.98, 2.61)], diabetes [1.42 (0.97, 1.86)]; behavioural-poor self-care [1.66 (0.84, 2.49)], and socio-economic-preference for maximal life extension at high cost for those with high education [1.98 (1.17, 2.80)]. Risk factors for unplanned hospital readmissions were similar. A higher hospital readmission rate increased the risk of mortality [1.86 (1.23, 2.50)]. Other risk factors for mortality were biologic-weak grip strength [3.65 (0.57, 6.73)], diabetes [2.52 (0.62, 4.42)], socio-economic-lower education [2.45 (0.37, 4.53)], and being married [2.53 (0.37, 4.69)]. Having a private health insurance [0.40 (0.08, 0.73)] lowered the risk for mortality. CONCLUSIONS: Risk factors for hospital readmissions and mortality are multifactorial. Many of these factors, such as weak grip strength, diabetes, poor self-care behaviours, are potentially modifiable and should be routinely assessed and managed in cardiac clinics and hospital admissions.

A Prospective Cohort Study of Medical Decision-Making Roles and Their Associations with Patient Characteristics and Patient-Reported Outcomes among Patients with Heart Failure.

OBJECTIVE: Among patients with heart failure (HF), we examined 1) the evolution of patient involvement in decision making over 2 y, 2) the association of patient characteristics with decision-making roles, and 3) the association of decision-making roles with distress, spiritual well-being, and quality of physician communication. METHODS: We administered the survey every 4 mo over 24 mo to patients with New York Heart Association class 3/4 symptoms recruited from inpatient clinics. The decision-making roles were categorized as no patient involvement, physician/family-led, joint (with family and/or physicians), patient-led, or patient-alone decision making. The associations between patient characteristics and decision-making roles were assessed using a mixed-effects ordered logistic regression, whereas those between patient outcomes and decision-making roles were investigated using mixed-effects linear regressions. RESULTS: Of the 557 patients invited, 251 participated in the study. The most common roles in decision making at baseline assessment were "no involvement" (27.53%) and "patient-alone decision making" (25.10%). The proportions of different decision-making roles did not change over 2 y (P = 0.37). Older age (odds ratio [OR] = 0.97; P = 0.003) and being married (OR = 0.63; P = 0.035) were associated with lower involvement in decision making. Chinese ethnicity (OR = 1.91; P = 0.003), higher education (OR = 1.87; P = 0.003), awareness of terminal condition (OR = 2.00; P < 0.001), and adequate self-care confidence (OR = 1.74; P < 0.001) were associated with greater involvement. Compared with no patient involvement, joint (ß = -0.58; P = 0.026) and patient-led (ß = -0.59; P = 0.014) decision making were associated with lower distress, while family/physician-led (ß = 4.37; P = 0.001), joint (ß = 3.86; P < 0.001), patient-led (ß = 3.46; P < 0.001), and patient-alone (ß = 3.99; P < 0.001) decision making were associated with better spiritual well-being. CONCLUSION: A substantial proportion of patients was not involved in decision making. Patients should be encouraged to participate in decision making since it is associated with lower distress and better spiritual well-being. HIGHLIGHTS: The level of involvement in medical decision making did not change over time among patients with heart failure. A substantial proportion of patients were not involved in decision making throughout the 24-mo study period.Patients' involvement in decision making varied by age, ethnicity, education level, marital status, awareness of the terminal condition, and confidence in self-care.Compared with no patient involvement in decision making, joint and patient-led decision making were associated with lower distress, and any level of patient involvement in decision making was associated with better spiritual well-being.

The impact of the COVID-19 pandemic on heart failure management: Global experience of the OPTIMIZE Heart Failure Care network.

During the COVID-19 pandemic, reductions in heart failure (HF) hospitalizations have been widely reported, and there is an urgent need to understand how HF care has been reorganized in countries with different infection levels, vaccination rates and healthcare services. The OPTIMIZE Heart Failure Care program has a global network of investigators in 42 countries, with first-hand experience of the impact of the pandemic on HF management in different care settings. The national coordinators were surveyed to assess: 1) the challenges of the COVID-19 pandemic for continuity of HF care, from both a hospital and patient perspective; 2) the organizational changes enacted to ensure continued HF care; and 3) lessons learned for the future of HF care. Contributions were obtained from 37 national coordinators in 29 countries. We summarize their input, highlighting the issues raised and using the example of three very different settings (Italy, Brazil, and Taiwan) to illustrate the similarities and differences across the OPTIMIZE program.

Effectiveness of a nurse-led temporal self-regulation theory-based program on heart failure self-care: A randomized controlled trial.

BACKGROUND: Heart failure self-care is crucial for sustainable heart failure management but its adherence remains poor worldwide. Despite having an intention to change, individuals often face difficulties in modifying existing lifestyle habits and sustaining change motivations. OBJECTIVES: To examine the effectiveness of a novel theory-driven nurse-led self-regulation program on improving heart failure self-care behaviours, future-thinking and behavioural automaticity. DESIGN: A two-arm randomized controlled trial. SETTINGS & PARTICIPANTS: 144 patients with heart failure were recruited from September 2018 to July 2019 at a tertiary hospital in Singapore. METHODS: Participants were randomly assigned to a self-regulation intervention (n = 72) or usual care group (n = 72). The three-month intervention was developed based on the temporal self-regulation theory and consisted of one face-to-face session, a print booklet and three reinforcement telephone follow-ups at week 3, 6 and 9. Outcomes were measured at baseline (T0), immediate after a three-month intervention (T1) and a further three-month follow-up (T2). heart failure self-care was measured using the Self-Care of Heart Failure Index (SCHFI) maintenance subscale, future-thinking was measured using the Consideration of Future Consequences Scale (CFCS) and behaviour automaticity was measured using the Self-Reported Behavioural Automaticity Index (SRBAI). The outcomes were compared between groups by using generalized estimating equations (GEE) based on intention-to-treat principle. RESULTS: No significant differences were found between the groups at baseline except for age. Participants were on average 61 years old, men (79.2%), had mild heart failure symptoms (50.7%) and had three comorbidities (66.0% dyslipidaemia; 65.3% hypertension; 61.8% history of myocardial infarction). Baseline scores indicated poor heart failure self-care (52.9±17.2, cut off ≥70). GEE results showed significantly higher heart failure self-care improvements in intervention group than control group at both T1 (regression coefficient, B = 13.9, 95% CI: 8.02 to 19.9, p < 0.001) and T2 (B = 8.34, 95% CI: 1.68 to 15.0, p = 0.014) after adjusting for gender, living alone, education level, comorbidity and age. Results also showed significantly higher increase in future-thinking (B[95% CI]=0.694[.123, 1.26], p = 0.017) and behaviour automaticity (B[95% CI]=0.656[.085, 1.23], p = 0.024) at T1 and only increase in behaviour automaticity (B[95% CI]=0.674[.099, 1.25], p = 0.022) at T2. However, only the differences in self-care scores at T1 remained significant after Bonferroni correction. No significant differences were found for intention, quality of life and clinical biomarkers. CONCLUSIONS: The program was effective in improving heart failure self-care and has potential for clinical implementation and generalisation to other chronic illnesses. Longer follow-up study is needed to uncover its long-term benefits on clinical outcomes.

Role in decision making among congestive heart failure patients and its association with patient outcomes: a baseline analysis of the SCOPAH study.

OBJECTIVE: We investigated the predictors of patient-experienced and preferred roles for decision making, and the association between patient-experienced role in decision making and patient outcomes among congestive heart failure (HF) patients in a multi-ethnic Asian population. METHODS: We surveyed 246 HF patients classified as New York Heart Association class 3/4. Multivariable regressions were used to analyse the associations between patient-experienced roles and patient outcomes. RESULTS: Patients who were male, attained higher education, and had a higher cognitive score were more likely to experience and prefer active roles in decision making. Younger patients and patients with lower symptom burden were more likely, while married patients were less likely to prefer leading decision making. Patients with collaborative (family and/or physician) decision making reported higher emotional well-being and sense of meaning/peace. Collaborative and patient-led decision making were associated with higher perceived control over illness. Those who were led by others or made decisions alone reported lower quality of physician communication. CONCLUSION: Collaborative decision making was associated with higher emotional well-being, sense of meaning/peace, and higher perceived control over illness among HF patients. PRACTICE IMPLICATIONS: Physicians should explain the benefits of shared decision making and encourage patients to participate in treatment decisions.

Using a hospital admission survey to estimate the burden of influenza-associated severe acute respiratory infection in one province of Cambodia-methods used and lessons learned.

BACKGROUND: Understanding the burden of influenza-associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza-associated SARI rates requires hospital-based surveillance data and a population-based denominator, which can be challenging to determine. OBJECTIVES: We present an application of the World Health Organization's recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza-associated SARI, with lessons learned to help others calculate similar estimates. METHODS: Using an existing SARI surveillance platform in Cambodia, we counted influenza-associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual-derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case-patients resided. We used HAS methods to adjust the district-level population denominator for the sentinel site and calculated the incidence rate of influenza-associated SARI by dividing the number of influenza-positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned. RESULTS: We estimated an adjusted influenza-associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza-associated SARI cases in Svay Rieng Province after extrapolation. CONCLUSIONS: Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza-associated SARI.

National burden of influenza-associated hospitalizations in Cambodia, 2015 and 2016.

INTRODUCTION: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia. METHODS: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population. RESULTS: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years. DISCUSSION: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity.

Ultrafiltration in patients with decompensated heart failure and diuretic resistance: an Asian centre's experience.

INTRODUCTION: Diuretics are the mainstay of therapy for restoring the euvolaemic state in patients with decompensated heart failure. However, diuretic resistance remains a challenge. METHODS: We conducted a retrospective cohort study to examine the efficacy and safety of ultrafiltration (UF) in 44 hospitalised patients who had decompensated heart failure and diuretic resistance between October 2011 and July 2013. RESULTS: Among the 44 patients, 18 received UF (i.e. UF group), while 26 received diuretics (i.e. standard care group). After 48 hours, the UF group achieved lower urine output (1,355 mL vs. 3,815 mL, p = 0.0003), greater fluid loss (5,058 mL vs. 1,915 mL, p < 0.0001) and greater weight loss (5.0 kg vs. 1.0 kg, p < 0.0001) than the standard care group. The UF group also had a shorter duration of hospitalisation (5.0 days vs. 9.5 days, p = 0.0010). There were no differences in the incidence of 30-day emergency department visits and rehospitalisations for heart failure between the two groups. At 90 days, the UF group had fewer emergency department visits (0.2 vs. 0.8, p = 0.0500) and fewer rehospitalisations for heart failure (0.3 vs. 1.0, p = 0.0442). Reduction in EQ-5D™ scores was greater in the UF group, both at discharge (2.7 vs. 1.4, p = 0.0283) and 30 days (2.5 vs. 0.3, p = 0.0033). No adverse events were reported with UF. CONCLUSION: UF is an effective and safe treatment that can improve the health outcomes of Asian patients with decompensated heart failure and diuretic resistance.