Evidence-based Heart Failure Therapies Research Articles

Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.

Rhythm management in patients with heart failure

Arrhythmias manifest frequently in individuals with heart failure, posing a notable threat of mortality and morbidity. While the prevention of sudden cardiac death through ICD therapy remains pivotal, accurate risk stratification remains a challenging task even in 2024. Recent data underscore the early consideration of catheter ablation for ventricular tachycardias. Although antiarrhythmic drug therapy serves as an ancillary measure for symptomatic patients, it does not confer prognostic advantages. The holistic management of arrhythmias in heart failure necessitates a systematic, multidimensional approach that initiates with evidence-based medical therapy for heart failure and integrates device-based and interventional therapies. Noteworthy clinical studies have illustrated the positive prognostic impact of early rhythm control strategies, particularly catheter ablation, in individuals managing heart failure and atrial fibrillation.

Enhancing implementation of evidence-based heart failure therapies in clinical practice: vital to modern medicine

Enhancing implementation of evidence-based heart failure therapies in clinical practice: vital to modern medicine

Integrating Cost into Shared Decision-Making for Heart Failure with Reduced Ejection Fraction (POCKET-COST-HF): A Trial Providing Out-of-Pocket Costs for Heart Failure Medications during Clinical Encounters

Evidence-based medical therapy for heart failure with reduced ejection fraction (HFrEF) often entails substantial out-of-pocket costs that can vary appreciably between patients. This has raised concerns regarding financial toxicity, equity, and adherence to medical therapy. In spite of these concerns, cost discussions in the HFrEF population appear to be rare, partly because out-of-pocket costs are generally unavailable during clinical encounters. In this trial, out-of-pocket cost information is given to patients and clinicians during outpatient encounters with the aim to assess the impact of providing this information on medication discussions and decisions. Cost-informed decision-making will be facilitated by providing access to patient-specific out-of-pocket cost estimates at the time of clinical encounter. Integrating Cost into Shared Decision-Making for Heart Failure with Reduced Ejection Fraction (POCKET-COST-HF) is a multicenter trial based at Emory Healthcare and University of Colorado Health. Adapting an existing patient activation tool from the EPIC-HF trial, patients and clinicians are presented a checklist with medications approved for treatment of HFrEF with or without patient-specific out-of-pocket costs (obtained from a financial navigation firm). Clinical encounters are audio-recorded, and patients are surveyed about their experience. The trial utilizes a stepped-wedge cluster randomized design, allowing for each site to enroll control and intervention group patients while minimizing contamination of the control arm. This trial will elucidate the potential impact of robust cost disclosure efforts and key information regarding patient and clinician perspectives related to cost and cost communication. It also will reveal important challenges associated with providing out-of-pocket costs for medications during clinical encounters. Acquiring medication costs for this trial requires an involved process and outsourcing of work. In addition, costs may change throughout the year, raising questions regarding what specific information is most valuable. These data will represent an important step towards understanding the role of integrating cost discussions into heart failure care. NCT04793880.

Evidence-based heart failure therapies at discharge of patients with acute coronary syndromes and reduced ejection fraction: Data from the ACSIS survey

Abstract Background Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS), even in the absence of overt HF. Few real-world data are available regarding early implementation of HF therapies in patients with ACS and reduced LVEF. Methods Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). Utilization of HF therapies at discharge or 90-days following ACS was analyzed in relation to LVEF [reduced ≤40% (n=406) or mildly-reduced 41-49% (n=255)] and short-term adverse outcomes. Results History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p<0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and BBC were used by >85% of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF≤40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41-49%, respectively, and SGLT2I in a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p=0.084. No association was observed between the number of HF drug classes, or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.Drug therapies for heart failure

Physical Frailty and Use of Guideline-Recommended Drugs in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND Guideline-recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life-saving therapy. We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis. METHODS AND RESULTS The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty-Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self-Efficacy for Walking-7 score, and Performance Measures for Activities of Daily Living-8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%; P for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05-1.43] per 1 category increase) and β-blockers (OR, 1.32 [95% CI, 1.06-1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84-1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all-cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08-2.98]) and III and IV (HR, 1.53 [95% CI, 1.01-2.32]) in the multivariate Cox proportional hazard model. CONCLUSIONS Prescription of guideline-recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with physical frailty.

Nurse-Led Heart Failure Clinics: A Snapshot of Counties Manukau in 2021

Heart failure is a complex clinical syndrome associated with significant morbidity and mortality. Evidence-based heart failure therapies are essential for improving outcomes of heart failure patients and nurse-led clinics can facilitate timely initiation and up-titration of these therapies. First-time and follow-up attendances to the nurse-led heart failure clinics were recorded in a database between May and December 2021. Demographic and diagnosis information was recorded, as well as the medication titration that occurred, the limitations to up-titration, and the follow-up plan. A total of 257 first visits took place, with a cumulative total of 542 visits for these patients. Patients were seen an average of 2.1 times over this time frame; 28% of patients were NZ Māori and 34% Pacific Islander. The average age was 57.9 years. Most patients (60%) have severe left ventricular impairment. Evidence-based heart failure medications were started during 96 clinic visits, and the dose was increased in 312 clinic visits. There were 177 instances where medications were unable to be started or up-titrated, due to the COVID-19 lockdown, and the resultant telehealth mode of delivery was a particular limitation. Nurse-led heart failure clinics are essential for helping patients become established and up-titrated on evidence-based heart failure therapies in a timely manner. While the COVID-19 lockdown had a significant impact in escalating therapy for patients, the data show that significant numbers of new patients are being seen, with a large volume of up-titration activity occurring in the clinics.

Improving implementation of evidence‐based therapies for heart failure

Treatment options for patients with heart failure have improved rapidly over the last few decades. Data from large scale clinical trials demonstrate that medical and device therapies can improve quality of life, reduce hospitalizations for acute heart failure, and reduce mortality. However, the use of many of these therapies in routine practice is remarkably low. There are many reasons for suboptimal implementation of evidence‐based therapies for heart failure, and we believe addressing the large gap between what can be accomplished in clinical trials versus routine practice is a critical and urgent public health issue. In this review, we outline reasons for this implementation gap and review recent studies attempting to address this issue. We also provide recommendations for future interventions and areas of clinical investigation to improve implementation for patients with heart failure.

The Role of AI in Characterizing the DCM Phenotype.

Dilated Cardiomyopathy is conventionally defined by left ventricular dilatation and dysfunction in the absence of coronary disease. Emerging evidence suggests many patients remain vulnerable to major adverse outcomes despite clear therapeutic success of modern evidence-based heart failure therapy. In this era of personalized medical care, the conventional assessment of left ventricular ejection fraction falls short in fully predicting evolution and risk of outcomes in this heterogenous group of heart muscle disease, as such, a more refined means of phenotyping this disease appears essential. Cardiac MRI (CMR) is well-placed in this respect, not only for its diagnostic utility, but the wealth of information captured in global and regional function assessment with the addition of unique tissue characterization across different disease states and patient cohorts. Advanced tools are needed to leverage these sensitive metrics and integrate with clinical, genetic and biochemical information for personalized, and more clinically useful characterization of the dilated cardiomyopathy phenotype. Recent advances in artificial intelligence offers the unique opportunity to impact clinical decision making through enhanced precision image-analysis tasks, multi-source extraction of relevant features and seamless integration to enhance understanding, improve diagnosis, and subsequently clinical outcomes. Focusing particularly on deep learning, a subfield of artificial intelligence, that has garnered significant interest in the imaging community, this paper reviews the main developments that could offer more robust disease characterization and risk stratification in the Dilated Cardiomyopathy phenotype. Given its promising utility in the non-invasive assessment of cardiac diseases, we firstly highlight the key applications in CMR, set to enable comprehensive quantitative measures of function beyond the standard of care assessment. Concurrently, we revisit the added value of tissue characterization techniques for risk stratification, showcasing the deep learning platforms that overcome limitations in current clinical workflows and discuss how they could be utilized to better differentiate at-risk subgroups of this phenotype. The final section of this paper is dedicated to the allied clinical applications to imaging, that incorporate artificial intelligence and have harnessed the comprehensive abundance of data from genetics and relevant clinical variables to facilitate better classification and enable enhanced risk prediction for relevant outcomes.

190 SARS-CoV-2 associated myopericarditis in a patient with previous myocarditis

AimsSevere acute respiratory syndrome coronavirus (SARS-CoV-2) is well described as being responsible for multi-organ involvement and SARS-CoV-2 cardiac involvement was observed since the beginning of the spread of the infection. However, there are no descriptions of acute myopericarditis in patient with previous myocarditis.Methods and resultsCardiac involvement was assessed with electrocardiographic and echocardiographic changes and with increased levels of cardiac high-sensitivity troponin T (hs-cTnT). Diagnosis was confirmed with cardiac magnetic resonance imaging (CMR) and coronary artery disease (CAD) was excluded with coronary angiography. A 53-years-old woman with hypokinetic cardiomyopathy due to a previous myocarditis and recent COVID-19 pneumonia reached the Emergency Department with chest pain and tachycardia in December 2020. Twelve-lead ECG was not conclusive and after detection of significative increase of hs-cTnT she was admitted to the Cardiology Department. Transthoracic echocardiography showed reduction of left ventricle ejection fraction, subendocardial bright appearance and mild pericardial effusion. Coronary angiography excluded obstructive CAD and CMR confirmed diagnosis of recent myocarditis and worsening of left and right ventricular ejection fraction compared to a previous CMR. Patient was treated with evidence-based therapy for heart failure, prednisone, intravenous immunoglobulins, ibuprofen, and colchicine. Cardiac biomarkers reduced within the normal range, symptoms improved, and the patient was discharged asymptomatic and haemodynamically stable.ConclusionsSARS-CoV-2, as already described in literature, can be associated with inflammatory cardiac involvement. This is the first report of SARS-CoV-2 associated myopericarditis in a patient with previous history of myocarditis and recent SARS-CoV-2 pneumonia. In our experience the patient was successfully treated with evidence-based therapy for heart failure and immunomodulation therapy.

Prescription Filling Patterns of Evidence-Based Medical Therapies for Heart Failure During the COVID-19 Pandemic in the United States

BackgroundMaintaining a steady medication supply during a public health crisis is a major health priority. We leveraged a large U.S. pharmacy-claims database to understand the use of evidence-based therapies in heart failure (HF) care during the coronavirus disease-2019 (COVID-19) pandemic.MethodsWe analyzed 27,027,650 individual claims from an all-payer pharmacy-claims database across 56,155 chain, independent and mail-order pharmacies in 14,164 zip codes in 50 states. Prescriptions dispensed (in 2-week intervals) of evidence-based HF therapies in 2020 were indexed to comparable timeframes in 2019. We normalized these year-to-year changes in HF medical therapies relative to those observed with a stable basket of drugs.ResultsFills of losartan, lisinopril, carvedilol, and metoprolol all peaked in the weeks of March 2020 and demonstrated trajectories thereafter that were relatively consistent with the reference set of drugs. Fills of spironolactone (+4%) and eplerenone (+18%) showed modest trends toward increased relative use during 2020. Fills of empagliflozin (+75%), dapagliflozin (+65%) and sacubitril/valsartan (+61%) showed striking longitudinal increases throughout 2020 that deviated substantially from year-to-year trends of the overall basket of drugs. For all 3 therapies, fills of all quantity sizes increased relatively throughout 2020. For both generic and brand-name therapies, prescription fill patterns from mail-order pharmacies increased substantially over expected trends beginning in March 2020ConclusionPrescription fills of most established generic therapies used in HF care were maintained, whereas those of sacubitril/valsartan and the sodium-glucose cotransporter-2 inhibitors steeply increased during the COVID-19 pandemic. These nationwide pharmacy claims data provide reassurance about therapeutic access, during a public health crisis, to evidence-based medications used in HF care.

Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid.

Despite improvements in pharmacotherapy, morbidity and mortality rates in community-based populations with chronic heart failure still remain high. The increase in medical complexity among patients with heart failure may be reflected by an increase in concomitant non-cardiovascular comorbidities, which are recognized as independent prognostic factors in this population. Heart failure and chronic kidney disease share many risk factors, and often coexist. The presence of kidney failure is associated with incremented risk of cardiovascular and non-cardiovascular mortality in heart failure patients. Chronic kidney disease is also linked with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. More targeted therapies would be important to improve the prognosis of patients with these diseases. In recent years, serum uric acid as a determinant of cardiovascular risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia are at increased risk of cardiac, renal and vascular damage and cardiovascular events. Moreover, elevated serum uric acid predicts worse outcome in both acute and chronic heart failure. While studies have raised the possibility of preventing heart failure through the use of uric acid lowering agents, the literature is still inconclusive on whether the reduction in uric acid will result in a measurable clinical benefit. Available evidences suggest that chronic kidney disease and elevated uric acid could worsen heart failure patients’ prognosis. The aim of this review is to analyse a possible utilization of these comorbidities in risk stratification and as a therapeutic target to get a prognostic improvement in heart failure patients.

Left-sided heart disease and risk of death in patients with end-stage kidney disease receiving haemodialysis: an observational study

BackgroundCardiovascular disease is the most common cause of death in patients with end-stage kidney disease on haemodialysis. The potential clinical consequence of systematic echocardiographic assessment is however not clear. In an unselected, contemporary population of patients on maintenance haemodialysis we aimed to assess: the prevalence of structural and functional heart disease, the potential therapeutic consequences of echocardiographic screening and whether left-sided heart disease is associated with prognosis.MethodsAdult chronic haemodialysis patients in two large dialysis centres had transthoracic echocardiography performed prior to dialysis and were followed prospectively. Significant left-sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%.ResultsAmong the 247 included patients (mean 66 years of age [95%CI 64–67], 68% male), 54 (22%) had significant left-sided heart disease. An LVEF ≤40% was observed in 31 patients (13%) and severe or moderate valve disease in 27 (11%) patients. The findings were not previously recognized in more than half of the patients (56%) prior to the study. Diagnosis had a potential impact on management in 31 (13%) patients including for 18 (7%) who would benefit from initiation of evidence-based heart failure therapy. After 2.8 years of follow-up, all-cause mortality among patients with and without left-sided heart disease was 52 and 32% respectively (hazard ratio [HR] 1.95 (95%CI 1.25–3.06). A multivariable adjusted Cox proportional hazard analysis showed that left-sided heart disease was an independent predictor of mortality with a HR of 1.60 (95%CI 1.01–2.55) along with age (HR per year 1.05 [95%CI 1.03–1.07]).ConclusionLeft ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage kidney failure on haemodialysis and are associated with a higher risk of death. For more than 10% of the included patients, systematic echocardiographic assessment had a potential clinical consequence.

Clinical presentation and outcomes of peripartum cardiomyopathy in the Middle East: a cohort from seven Arab countries.

AimsPublished data on the clinical presentation of peripartum cardiomyopathy (PPCM) are very limited particularly from the Middle East. The aim of this study was to examine the clinical presentation, management, and outcomes of patients with PPCM using data from a large multicentre heart failure (HF) registry from the Middle East.Methods and resultsFrom February to November 2012, a total of 5005 consecutive patients with HF were enrolled from 47 hospitals in 7 Middle East countries. From this cohort, patients with PPCM were identified and included in this study. Clinical features, in‐hospital, and 12 months outcomes were examined. During the study period, 64 patients with PPCM were enrolled with a mean age of 32.5 ± 5.8 years. Family history was identified in 11 patients (17.2%) and hypertension in 7 patients (10.9%). The predominant presenting symptom was dyspnoea New York Heart Association class IV in 51.6%, class III in 31.3%, and class II in 17.2%. Basal lung crepitations and peripheral oedema were the predominant signs on clinical examination (98.2% and 84.4%, respectively). Most patients received evidence‐based HF therapies. Inotropic support and mechanical ventilation were required in 16% and 5% of patients, respectively. There was one in‐hospital death (1.6%), and after 1 year of follow‐up, nine patients were rehospitalized with HF (15%), and one patient died (1.6%).ConclusionsA high index of suspicion of PPCM is required to make the diagnosis especially in the presence of family history of HF or cardiomyopathy. Further studies are warranted on the genetic basis of PPCM.

Current and Emerging Issues in the Management of Heart Failure in Primary Care

Describe the epidemiology of heart failure in people with diabetes mellitus. Implement evidence-based nonpharmacologic and pharmacologic therapies for heart failure with preserved ejection fraction and heart failure with reduced ejection fraction as recommended in current guidelines. Characterize the role of glucose-lowering medications, focusing on the sodium glucose cotransporter-2 inhibitors, for the treatment of people with type 2 diabetes mellitus.

Effect of Dapagliflozin in Patients With HFrEF Treated With Sacubitril/Valsartan: The DAPA-HF Trial

ObjectivesThis study assessed the efficacy and safety of dapagliflozin in patients who were or were not taking sacubitril/valsartan at baseline in the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial. BackgroundBoth the angiotensin receptor neprilysin-inhibitor sacubitril/valsartan and the sodium glucose co-transporter 2 inhibitor dapagliflozin reduced cardiovascular death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Whether either of these classes of drugs influences the effectiveness or safety of the other remains unknown. MethodsDAPA-HF was a 4,744 patient trial that compared dapagliflozin with placebo in patients with HFrEF. Patients were analyzed according to whether they were taking sacubitril/valsartan at randomization. The efficacy of dapagliflozin on the primary composite outcome (CV death or episode of worsening heart failure), its components, and all-cause death was examined according to sacubitril/valsartan and the interaction tested. Predefined safety outcomes were examined by sacubitril/valsartan group. ResultsA total of 508 patients (10.7%) enrolled in DAPA-HF were treated with sacubitril/valsartan at baseline. Patients prescribed sacubitril/valsartan were more likely to be from North America or Europe, to have lower ejection fractions and systolic and diastolic blood pressures, but were similar with respect to age, New York Heart Association functional class, history of diabetes, and use of other evidence-based HF therapies. The benefit of dapagliflozin compared with placebo was similar in patients taking sacubitril/valsartan (hazard ratio: 0.75; 95% confidence interval 0.50 to 1.13) compared with those not taking sacubitril/valsartan (hazard ratio: 0.74; 95% confidence interval 0.65 to 0.86) for the primary endpoint of cardiovascular death or worsening HF; similar findings were observed for secondary endpoints. All measures of safety, including episodes related to hypovolemia, were similar among patients randomized to dapagliflozin or placebo, whether they received background sacubitril/valsartan. ConclusionsDapagliflozin was similarly efficacious and safe in patients who were and who were not taking sacubitril/valsartan in the DAPA-HF trial, which suggested that the use of both agents together could further lower morbidity and mortality in patients with HFrEF. (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure [DAPA-HF]; NCT03036124)

Clinical Presentation and Outcomes of Peri-Partum Cardiomyopathy in the Middle-East: A Report from Seven Arab Countries

Background: Published data on the clinical presentation of peripartum cardiomyopathy (PPCM) are very limited particularly from the Middle East. The aim of this study was to examine the clinical presentation, management and outcomes of patients with PPCM using data from a large multicentre heart failure (HF) registry from the Middle-East. Methods: From February to November, 2012, a total of 5005 consecutive patients with HF were enrolled from 47 hospitals in 7 Middle East countries. From this cohort, patients with PPCM were identified and included in this study. Clinical features, in-hospital and 12 months outcomes were examined. Findings: During the study period 64 patients with PPCM were enrolled with a mean age of 32.5 ±5.8 years. Family history was identified in 11 patients (17.2%) and hypertension in 7 patients (10.9%). The predominant presenting symptom was dyspnea with NYHA class VI in 51.6%, class III in 31.3% and class II in 17.2%. Basal lung crepitations and peripheral edema were the predominant signs on clinical examination (98.2% and 84.4%, respectively). Most patients received evidence-based HF therapies. Inotropic support and mechanical ventilation were required in 16% and 5% of patients, respectively. There was one in-hospital death (1.6%), and over one-year of follow-up 9 patients were re-hospitalized with HF (15%) and one patient died (1.6%). Interpretation: A high index of suspicion of PPCM is required to make the diagnosis especially in the presence of family history of HF or cardiomyopathy. Further studies are warranted on the genetic basis of PPCM. Trial Registration: The study was registered at clinicaltrials.gov with the number NCT01467973. Funding Statement: Gulf CARE was an investigator-initiated study conducted under the auspices of the Gulf Heart Association and funded by Servier, Paris, France; and (for centres in Saudi Arabia) by the Saudi Heart Association [The Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia (Research group number: RG -1436-013)]. The publication of this article was funded by the Qatar National Library. Declaration of Interests: The authors report no relationships that could be construed as a conflict of interest. Ethics Approval Statement: Study ethical approval was obtained from all concerned authorities in the recruiting centers. Informed consent was obtained from all patients.

The hospital frailty risk score in patients with heart failure is strongly associated with outcomes but less so with pharmacotherapy.

Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. To explore the relationships between frailty, pharmacotherapy and outcomes in heart failure (HF). Retrospective cohort study of all adults in Alberta, Canada hospitalized for the first time for HF between 2004 and 2016. Frailty was defined using the Hospital Frailty Risk Score (HFRS). In 26626 patients (mean age 77.4years), the 8887 (33.4%) defined as frail (HFRS≥5) were older, had higher Charlson scores and more prior emergency department visits or hospitalizations. The HFRS and the Charlson Score were only weakly correlated (r=0.35). Whilst more common in older patients (41.4% of patients 80 or older), frailty was present in 22.4% of patients younger than 65. Frail patients had longer lengths of stay and worse outcomes postdischarge, but adding the HFRS to age, sex and Charlson score did not improve prediction of events (c-statistics 0.69 for 30-day mortality after admission, and 0.54 for 30-day readmission/ED visit/or death after discharge). Frail patients younger than 65 were significantly more likely than nonfrail patients 80 or older to be prescribed high-dose evidence-based HF therapies (27.1% vs. 22.2%, P=0.003). Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.

P773Initiation of sacubitril/valsartan and optimisation of evidence-based heart failure therapies after hospitalisation for acute decompensated heart failure: An analysis of the TRANSITION study

Abstract Background Optimisation of chronic heart failure (HF) therapy remains the key strategy to improve outcomes after hospitalisation for acute decompensated HF (ADHF) with reduced ejection fraction (HFrEF). Initiation and uptitration of disease-modifying therapies is challenging in this vulnerable patient population. We aimed to describe the patterns of treatment optimisation including sacubitril/valsartan (S/V) in the TRANSITION study. Methods TRANSITION (NCT02661217) was a randomised, open-label study comparing S/V initiation pre- vs. post-discharge (1–14 days) in patients admitted for ADHF after haemodynamic stabilisation. The primary endpoint was the proportion of patients achieving 97/103 mg S/V twice daily (bid) at 10 weeks post-randomisation. Up-titration of S/V was as per label. Information on dose of S/V and on the use of concomitant HF medication was collected at each study visit up to week 26. Results A total of 493 patients received at least one dose of S/V in the pre-discharge arm and 489 patients in the post-discharge arm. One month after randomisation, 45% of patients in the pre-d/c arm vs. 44% in the post-discharge arm used 24/26 mg bid starting dose and 42% vs. 40% were on 49/51 mg S/V bid, respectively. At week 10, 47% of patients had achieved the target dose in the pre-discharge arm vs. 51% in the post-discharge arm. At the end of the follow-up at 26 weeks, the proportion of patients on S/V target dose further increased to 53% in the pre-discharge and 61% in the post-discharge arm (Figure 1). At week 10, the mean dose of S/V was 132 mg in the pre-discharge arm and 136 mg in the post-discharge arm, and at week 26, it was 140 mg and 147 mg, respectively. Before hospital admission, 52% and 54% of the patients received a beta-blocker (BB) in the pre-discharge and post-discharge group, respectively, and 42% in both arms received a mineralcorticoid receptor antagonist (MRA). At time of discharge, 68% and 71%% of the patients received a BB and 68% and 65% an MRA, in the pre-discharge and post-discharge groups, respectively. These proportions remained stable to week 10 and week 26. Uptitration of sacubitril/valsartan Conclusions In the vulnerable post-ADHF population, initiation of S/V and up-titration to target dose was feasible within 10 weeks in half of the patients alongside with a 20% increase in the use of other disease-modifying medications that remained stable through the end of the 6-month follow-up. Acknowledgement/Funding The TRANSITION study was funded by Novartis

Secondary mitral regurgitation: percutaneous edge-to-edge repair on the cutting edge?

Secondary mitral regurgitation commonly complicates heart failure. Although the evidence for its management is most robust for treating the underlying cardiomyopathy, treatment aimed at additionally reducing the severity of mitral regurgitation with a percutaneous edge-to-edge device, MitraClip, has recently emerged. Despite the use of contemporary evidence-based heart failure therapies, patients with secondary mitral regurgitation and heart failure continue to remain at high risk for adverse clinical events; in both the MITRA-FR and COAPT trials, an extremely high event rate was evident in the medically managed arms over the respective 12-24-month follow-up. Data supporting the use of MitraClip to mitigate adverse outcomes in secondary mitral regurgitation is, however, conflicting. In MITRA-FR no difference was noted between MitraClip compared with the medically managed arm for the composite of all-cause death or heart failure hospitalization at 12 months. However, in COAPT, a significant reduction in the rate of heart failure re-hospitalization over 2 years was evident with MitraClip compared with medical therapy alone. Recommendations exist for the use of MitraClip in patients with primary mitral regurgitation and prohibitive surgical risk. However, with the divergent results of two recent high-quality randomized trials, its role in patients with secondary mitral regurgitation remains controversial.