Target Doses Of Beta-blockers Research Articles

ANTIHYPERTENSIVE DRUGS IN CHRONIC HEART FAILURE IN THE CZECH REPUBLIC, FOCUSING ON BETA-BLOCKERS

Objective: Hypertension is a very common comorbidity in patients with heart failure. Beta-blockers (BB) are the first choice drug together with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF), reducing morbidity and mortality. Design and method: Data were collected in the FARmacology and NeuroHumoral Activation Registry (FAR NHL). Patients with chronic heart failure with left ventricular ejection fraction (LVEF) < 50% for at least one month were included. Results: 1,100 patients with a mean age of 65 years, 80.8% male, were included. The mean systolic blood pressure was 128.0 mm Hg, mean diastolic blood pressure was 80.0 mm Hg. Of all patients, 20% received low dose of beta-blocker (LD), 57% medium dose (MD) and 17% high dose (HD), 6.2% did not receive BB. The higher the blood pressure (LD 124/ 77; MD 129/ 80; HD 132/ 82 mm Hg; p < 0.001), LV EF (LD 29.5; MD 30.5; HD 32.0%; p = 0.003), creatinine clearance (LD 78.7; MD 87.8; HD 91.1 ml/min; p = 0.001) or weight of the patients, the higher the BB dose they received (LD 83.2; MD 88.7; HD 93.5 kg; p < 0.001). The lower the NT-proBNP, the higher the BB dose patients received (LD 767; MD 456; HD 314 pg/ml; p < 0.001). The presence of atrial fibrillation (AF) did not affect the BB dose. Patients with AF were more likely to be treated with digoxin or a combination of digoxin and BB than patients without AF (p < 0.001). Conclusions: According to FAR NHL registry, almost 94% of patients with HFrEF receive BB. A total of 17% of patients take the target dose of BB. If a patient has BB, he/she is treated with the recommended preparation in more than 99% of cases. The more severe the disease, as reflected by lower BP, creatinine clearance, LV EF, weight or higher NT-proBNP, the lower the dose of beta-blockers the patient receives and tolerates.

Abstract 17715: Heart Rate Reduction Alone Produces Reverse Remodeling in Heart Failure Patients Refractory to Beta-Blockers: The PROBE-IT Trial

In a 2-center trial ( P ulse R eduction o n Be ta-Blocker and I vabradine T herapy (PROBE-IT)) we tested the hypothesis that failure to adequately reduce heart rate (HR) contributes to non-response to beta-blockers. Twenty-two dilated cardiomyopathy patients (DCM) with a sinus rhythm (SR) heart rate (HR) ≥70 bpm without reverse remodeling after target doses of beta-blockers were randomized 2:1 to 5±2.5 mg b.i.d of ivabradine (IVB) or matching placebo, and treated for 24 weeks with continuation of beta-blockers. Echocardiograms for LVEF measurements and endomyocardial biopsies for measurement of global gene expression by RNA-Sequencing were performed at baseline and end of study. The protocol design aimed for approximately equal numbers of patients with a HR reduction (HRι) and a control group with no change in HR (HRν), with the predefined statistical analysis plan comparing subjects above and below the median HR change. Characteristics and changes from baseline in the 17 patients who completed the trial were (*P <0.05, † P <0.01 vs. HRν):HRν patients had a longer duration of HF,, 112 months vs. 35 months in HRι (P = 0.005). In HRι vs. HRν, gene expression findings included 18 mRNAs at a P <0.0005 and 39 at a P of <0.001 with higher abundance, and 34 (P <0.0005) and 94 (P <0.001) lower abundance. The classification of these genes was distinct from molecular changes described for reverse remodeling from beta-blockers alone, with only a 2.1% overlap. Gene expression changes that could have contributed to reverse remodeling in HRι included: increases in NRG1 (neuregulin 1), PP1R3C (protein phosphatase 1), and multiple mitochondrial electron transport genes; and lower expression of genes encoding cardiotrophin-1 cytokines (CTF1 and CLCF1). Conclusions: In NDC patients meeting the PROBE-IT entry criteria, HR lowering produces a substantial increase in LVEF accompanied by gene expression changes that differ from those associated with beta-blocker therapy.

Use of heart failure medications in older individuals and associations with cognitive impairment

BackgroundTo achieve the best treatment of heart failure, it is important to use all recommended drugs at their target doses. Given that underuse of medications can occur in individuals with cognitive impairment, we investigated the filled prescriptions and target doses of heart failure medication for older individuals with and without cognitive impairment as well as associated factors.MethodsThe study was based on two separate datasets. The first dataset, which was based on data from questionnaires sent to nursing homes in Sweden, included 405 individuals with heart failure. The data were linked with the Swedish Prescribed Drug Register and the National Patient Register to obtain information regarding filled prescriptions of heart failure medications and heart failure diagnoses among the population. In the second dataset, medical records of individuals aged 75 years or older admitted to a hospital in northern Sweden were reviewed and individuals with heart failure were identified. Target doses of heart failure medications were evaluated in 66 individuals who lived at home.ResultsFilled prescriptions of mineralocorticoid receptor antagonists and loop diuretics were significantly more common in individuals without cognitive impairment (OR 1.087; 95% CI 1.026–1.152, p < 0.05) and (OR 1.057; 95% CI 1.017–1.098, p < 0.05), respectively. There were no significant differences between individuals with and without cognitive impairment in terms of achieving target doses for any of the drug classes. A higher age was associated with fewer filled prescriptions and less ability to reach the target doses of beta blockers (OR 0.950; 95% CI 0.918–0.984, p < 0.05) and (OR 0.781; 95% CI 0.645–0.946, p < 0.05), respectively.ConclusionsOur results suggest that individuals with cognitive impairment are partly undertreated for heart failure in that they had fewer filled prescriptions of important heart medications. Separately, the relatively low proportion of older individuals reaching target doses is an important observation and indicates that treatment of heart failure could be further optimised among older individuals.

Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study.

The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12months. Among the patients, 69.3% were male, with a median age of 49years. The baseline systolic blood pressure (SBP) was 117.6±18.3mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P<0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P<0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P<0.001] during 12month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P<0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up. Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Heart failure treatment in patients with and without obesity with an ejection fraction below 50.

The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

A novel algorithm for rapid sequence optimization of guideline directed medical therapy for heart failure with reduced ejection fraction

Abstract Introduction Current guidelines for management of Heart Failure with Reduced Ejection Fraction (HFrEF) recommend Beta-blockers, Angiotensin Receptor Neprilysin Inhibitors (ARNI), Mineralocorticoid Receptor Antagonists (MRA) and SGLT2 inhibitors. However, guideline-directed medical therapies (GDMT) remain underutilized. The 2018 CHAMP-HF registry of HFrEF patients demonstrated that only 1% of patients were treated with target doses of Beta-blockers, MRA and ACE-inhibitors (ACE-I) and Angiotensin Receptor Blocker (ARB) or ARNI. Historically, HFrEF therapies were initiated and up-titrated sequentially. Recent expert commentary has suggested a more aggressive approach of initiating all 4 classes of therapy at low doses after which patients should be up-titrated to target dose Purpose This study tested a novel, virtual HFrEF optimization program with the goal of achieving GDMT using a novel “rapid sequence” algorithm. Methods We conducted a single center study at a regional cardiovascular centre using a prospective pre-post design. NYHA class II/III HFrEF patients referred from both inpatient and outpatient settings were enrolled in a virtual 3-month HFrEF optimization program. All participants underwent an initial consult with a program nurse and cardiologist. After this, all patients were seen remotely by a nurse every two weeks for adjustment of HFrEF medications. At week 1, patients started on ARNI and SGLT2i. After week 3, Beta-Blocker was initiated. After week 5, MRA was initiated. Following this, medications were up-titrated every two weeks, based on clinical judgement of the overseeing cardiologist. Vital signs and bloodwork were obtained after all medication adjustments. In addition, all patients were seen once weekly by a kinesiologist for lifestyle optimization and counselling. Results From April 2020 to January 2021, 297 NYHA class II/III HFrEF patients enrolled in the virtual HFrEF optimization program. Mean age was 69 and 63% were male. Mean ejection fraction was 28% and 54% had ischemic cardiomyopathy. At intake, the proportion of patients prescribed maximally-tolerated dosage was 64% for Beta-Blockers, 7% for MRA, 1% for ARNI and 1% for SGLT2i. At 3-month follow-up, maximally-tolerated dose was prescribed in 84% of patients for beta-blockers (p&amp;lt;0.01), 58% for MRA (p&amp;lt;0.01), 77% for SGLT2i (p&amp;lt;0.01) and 96% for ARNI (p&amp;lt;0.01). 39% of patients achieved maximal doses of all 4 classes of medications at follow-up. No medication-related adverse events were reported and 18 patients were hospitalized for HF exacerbation during study follow-up. Conclusions This study demonstrates that a program using aggressive GDMT initiation can safely and effectively improve uptake of therapy in HFrEF patients. Future research should examine HFrEF “rapid sequence” optimization on patient outcomes in a randomized setting. Funding Acknowledgement Type of funding sources: None.

The Prevalence and Characteristic of Patients Achieve Target Doses of Medications Used to Treat Heart Failure with Reduced Ejection Fraction at Heart Failure Clinic

OBJECTIVES: To determine the prevalence and characteristics of patients who achieved target doses of angiotensin converting enzyme inhibitors (ACEIs)/ angiotensin II receptor blockers (ARBs), beta-blocker, and mineralocorticoid receptor antagonists (MRAs). MATERIALS AND METHODS: A retrospective chart review study of heart failure with reduced ejection fraction (HFrEF) patients who received ACEIs/ARBs, beta-blockers, or MRAs and follow-up more than four times at the heart failure outpatient clinic, Chonburi hospital from February 1st, 2017 to February 29th, 2020. Patient data were retrieved from electronic medical records. Two authors collected data into record form (CRF) independently. Achieving target doses was defined by recommended doses according to the ACC/AHA/HFSA Guideline, 2017. The comparison of continuous data was conducted with the Mann-Whitney U test. Pearson Chi-Square and Fisher’s exact test were used for the comparison of categorical data. RESULTS: Patients who achieved target doses of ACEIs/ARBs, beta-blockers and MRAs was 73.3%, 55.3%, and 7.1% respectively. Patients’ characteristics of achieved target doses of ACEIs/ARBs were higher baseline left ventricular ejection fractions (p = 0.026). Younger age (p = 0.016), body mass index (BMI) ≥ 23 kg/m2 (p = 0.037; OR 5.3) and serum creatinine ≤ 2 mg/dL (p = 0.004) were the characteristics of patients who achieved target doses of beta-blockers. CONCLUSION: Most patients in heart failure clinic achieved target doses of ACEIs/ARBs followed by beta-blockers but only a few patients for MRAs. Patient and medical characteristics were different in target doses achievable.

The Impact Of Race And Ethnicity On Clinical Outcomes In Patients With Heart Failure(On Behalf Of The Guide-IT Steering Committee)

Introduction Black and Hispanic patients (pts) with heart failure (HF) are under-represented in clinical trials. Thus, it has been challenging to understand the impact of race and/or ethnicity on clinical outcomes and responsiveness to treatment in pts with HF. Hypothesis The data in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial was used to explore racial and ethnic differences in clinical outcomes. Pts were included who were event-free at 90 days and had data on attainment of guideline-directed triple therapy (GDMT, defined as greater than 50% target dose of beta-blocker, ACEI or ARB, and any MRA dose) or target NT-proBNP ≤ 1000 pg/mL. We postulated that Black pts would have worse clinical outcomes than non-Black pts, and that Hispanic pts would have worse outcomes than non-Hispanic pts. Methods Cox proportional hazards models were used to estimate the impact of race and ethnicity on mortality and HF hospitalization. These models accounted for 3-month achievement of GDMT or target NT-proBNP, as well as previously identified prognostic characteristics. Results Of the 733 patients included, 35% were Black and 6% were Hispanic. Black pts were younger, had more co-morbidities, lower EF, and higher NYHA class vs. non-Black pts. After accounting for GDMT attainment, Black pts were at a higher risk than non-Black pts for HF hospitalization (HR=1.97, 95% CI = 1.41-2.77, p < 0.0001), but not mortality (HR = 0.70, 95% CI = 0.39-1.26, p = 0.23) (Figures 1A-1B). Hispanic pts trended towards a higher risk than non-Hispanic pts for HF hospitalization (HR=1.83, 95% CI = 0.82-4.08, p = 0.14), but not for death (HR = 0.61, 95% CI = 0.18-2.09, p = 0.43) (Figures 1C-1D). Similar patterns were observed when accounting for target NT-proBNP. Estimated effects on mortality were limited by the low mortality rate (14%). Conclusion After adjusting for GDMT or target NT-proBNP attainment, as well as prognostic characteristics, Black HF pts had a higher risk of HF hospitalization than non-Black pts. There was also a trend for higher HF hospitalization risk for Hispanic pts compared to non-Hispanic pts . Mortality results were indeterminate, but point estimates did not support an excess mortality risk for Black or Hispanic pts. Black and Hispanic patients (pts) with heart failure (HF) are under-represented in clinical trials. Thus, it has been challenging to understand the impact of race and/or ethnicity on clinical outcomes and responsiveness to treatment in pts with HF. The data in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial was used to explore racial and ethnic differences in clinical outcomes. Pts were included who were event-free at 90 days and had data on attainment of guideline-directed triple therapy (GDMT, defined as greater than 50% target dose of beta-blocker, ACEI or ARB, and any MRA dose) or target NT-proBNP ≤ 1000 pg/mL. We postulated that Black pts would have worse clinical outcomes than non-Black pts, and that Hispanic pts would have worse outcomes than non-Hispanic pts. Cox proportional hazards models were used to estimate the impact of race and ethnicity on mortality and HF hospitalization. These models accounted for 3-month achievement of GDMT or target NT-proBNP, as well as previously identified prognostic characteristics. Of the 733 patients included, 35% were Black and 6% were Hispanic. Black pts were younger, had more co-morbidities, lower EF, and higher NYHA class vs. non-Black pts. After accounting for GDMT attainment, Black pts were at a higher risk than non-Black pts for HF hospitalization (HR=1.97, 95% CI = 1.41-2.77, p < 0.0001), but not mortality (HR = 0.70, 95% CI = 0.39-1.26, p = 0.23) (Figures 1A-1B). Hispanic pts trended towards a higher risk than non-Hispanic pts for HF hospitalization (HR=1.83, 95% CI = 0.82-4.08, p = 0.14), but not for death (HR = 0.61, 95% CI = 0.18-2.09, p = 0.43) (Figures 1C-1D). Similar patterns were observed when accounting for target NT-proBNP. Estimated effects on mortality were limited by the low mortality rate (14%). After adjusting for GDMT or target NT-proBNP attainment, as well as prognostic characteristics, Black HF pts had a higher risk of HF hospitalization than non-Black pts. There was also a trend for higher HF hospitalization risk for Hispanic pts compared to non-Hispanic pts . Mortality results were indeterminate, but point estimates did not support an excess mortality risk for Black or Hispanic pts.

Diabetes and treatment of chronic heart failure in a large real-world heart failure population.

AimsAlthough diabetes mellitus (DM) is a common co‐morbidity in chronic heart failure (HF) patients, European data on concurrent HF and DM treatment are lacking. Therefore, we have studied the HF treatment of patients with and without DM. Additionally, with the recent breakthrough of sodium–glucose cotransporter 2 (SGLT2) inhibitors in the field of HF, we studied the potential impact of this new drug in a large cohort of HF patients.Methods and resultsA total of 7488 patients with chronic HF with a left ventricular ejection fraction <50% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on diabetic status and background HF therapy. Average age of the total population was 72.8 years (±11.7 years), and 64% of the patients were male. Diabetes was present in 29% of the patients (N = 2174). Diabetics had a worse renal function (mean estimated glomerular filtration rate 56 vs. 61 mL/min/1.73 m2, P < 0.001). Renin–angiotensin system inhibitors were less often prescribed in diabetics compared with non‐diabetics (79% vs. 82%, P = 0.001), while no significant differences regarding other guideline‐recommended HF drugs were found. Target doses of beta‐blockers (23% vs. 16%, P < 0.001), renin–angiotensin system inhibitors (47% vs. 43%, P = 0.009), and mineralocorticoid receptor antagonists (57% vs. 51%, P = 0.005) were more often prescribed in diabetics than non‐diabetics. Based on the latest trials on SGLT2 inhibitors, 31–64% of all HF patients would fulfil the eligibility or enrichment criteria (with vs. without N‐terminal prohormone BNP criterion).ConclusionsIn this large real‐world HF registry, a high prevalence of DM was observed and diabetics more often received guideline‐recommended target doses. Based on current evidence, the majority of patients would fulfil the enrichment criteria of SGLT2 trials in HF and the impact of this new drug class will be large.

Abstract 14276: Bridging The Gap To Optimal Dosing For Guideline-directed Medical Therapy For Patients With Heart Failure And Reduced Ejection Fraction

Introduction: The key to improving heart failure (HF) outcomes and its ultimate impact on reducing health care costs include the initiation, optimization, and maintenance of guideline-directed medical therapy (GDMT) in patients with Heart Failure and Reduced Ejection Fraction (HFrEF). The ACC/AHA/HFSA guidelines recommend maximum tolerated doses for these patients unless contraindicated. Despite widespread knowledge, there is underutilization of GDMT at recommended target doses in eligible patients. Hypothesis: Majority of eligible patients (&gt;50%) in our safety-net HF Clinic are on optimal doses of GDMT. Methods: We conducted a retrospective analysis of GDMT use in patients who were diagnosed with HFrEF between January 1 to March 31, 2019, and completed at least two HF clinic visits in 2019. The primary outcomes were the percent of patients on optimal doses of: (1) beta blockers, (2) renin-angiotensin-aldosterone system (RAAS) inhibitors, and (3) mineralocorticoid antagonists (MRAs). Optimal dose was defined &gt;/= 50% of target dose or maximum tolerated dose. Results: Our cohort of 227 patients was predominantly male (70%), African American (94%) with mean age of 59 +/- 11 years. Most patients were on beta blockers (96%) and RASS inhibitors (88%). Only 11% were on Angiotensin Receptor-Neprilysin Inhibitors(ARNI), and 30% on MRAs. Only 52%, 43%, and 20% of patients were prescribed target doses of beta blockers, ACEI/ARBs, and MRAs respectively. Conclusions: GDMT dosing in our safety-net HF Clinic was suboptimal. Based on these findings, we are implementing a quality improvement process to facilitate early initiation and up-titration of GDMT with the overall goal of reducing the morbidity and mortality in our patient population.

Abstract 11716: The Impact of a Virtual Multi-Disciplinary Heart Failure Optimization Program on Achievement of Guideline-Directed Therapy

Introduction: Current guidelines for management of Heart Failure with Reduced Ejection Fraction (HFrEF) recommend Beta-blockers, Angiotensin Receptor Neprilysin Inhibitors (ARNI), Mineralocorticoid Receptor Antagonists (MRA) and SGLT2 inhibitors. However, guideline-directed medical therapies (GDMT) remain underutilized. The 2018 CHAMP-HF registry of HFrEF patients demonstrated that only 1% of patients were treated with target doses of Beta-blockers, MRA and ACE-inhibitors (ACE-I) and Angiotensin Receptor Blocker (ARB) or ARNI. Methods: We conducted a single center study of a virtual, multidisciplinary HFrEF optimization program for achieving GDMT. Patients referred from both inpatient and outpatient settings were enrolled in this 3-month initiative. After an initial cardiology consult, patients were seen virtually once weekly by a kinesiologist for lifestyle optimization and virtually by a nurse once every two weeks for up-titration of guideline-based therapies, with cardiologist oversight. Vital signs, serum creatinine and electrolytes were obtained after medication adjustment. Results: Over 9 months, 297 patients were referred and all enrolled in the virtual HFrEF optimization program. Mean age was 69 and 63% were male. Mean ejection fraction was 28% and 54% had ischemic cardiomyopathy. At initial visit, the frequency of patients prescribed optimal dosage for Beta-Blockers was 64%, 7% for MRA and 1% for SGLT2 inhibitors. 88% were prescribed ACE-I or ARB while 1% of patients were on ARNI. At 3 month follow-up, the frequency of patients prescribed optimal dosage for Beta-Blockers was 84% (p&lt;0.01), 58% for MRA (p&lt;0.01), 77% for SGLT2 inhibitors (p&lt;0.01) and 96% for ARNI (p&lt;0.01). Overall, 39% of patients achieved maximal doses of all 4 classes of medications at 3 month follow-up. During the study period, there were no hospitalizations or medication adverse events among participants. The most common causes of failure to achieve GDMT was chronic kidney disease or drug cost or coverage. Conclusions: This study demonstrates that a virtual multidisciplinary program can safely and effectively improve usage of GDMT in HFrEF patients. Further studies should examine the effect of similar interventions on patient outcomes in a randomized format.

Role of Guideline Directed Medical Therapy Doses and Optimization in Patients Hospitalized With Decompensated Systolic Heart Failure

Despite significant advances in evidence-based treatments for heart failure with reduced ejection fraction (HFrEF), the use of guideline directed medical therapy (GDMT) at recommended doses remains suboptimal. We examine the usage and modification of inpatient GDMT and its effect on outcomes in patients hospitalized with a diagnosis of acute on chronic HFrEF between 2013 and 2018. Overall use and modification of GDMT, which included heart failure appropriate beta-blockers (BB), renin-angiotensin system inhibitors (RASi) and aldosterone blockers (MRA) during the hospitalization were collected. Target dosages were based on guideline recommendations. Primary endpoints included 30-day hospitalization-free survival and 1-year survival. Among 1,655 patients, discharge use of BB, RASi, and MRA was 73.4%, 55.9% and 13.8%, respectively. Upon discharge, ≥50% target dose of BB, RASi, and MRA was used in 25.3%, 15.6%, and 13.7%, respectively. In multivariable analyses, there was a statistically significant improvement in 1-year survival and 30-day hospitalization-free survival in patients discharged on increasing number of medication classes optimized at ≥50% target dose (per extra medication, HR 0.74, 0.64-0.86, p <0.001, and HR 0.73, 0.62-0.86, p = 0.0002), respectively. Initiation and/or uptitration of BB and RASi was associated with improved 30-day hospitalization-free survival and 1-year survival, (HR 0.73 (0.57-0.92), p = 0.0087; HR 0.62 (0.46-0.82), p <0.001) for BB and (HR 0.77 (0.62-0.95), p <0.001; HR 0.62 (0.48-0.80), p <0.001) for RASi, respectively. In conclusion, inpatient optimization of GDMT in acute HFrEF is feasible and associated with improved 30-day hospitalization-free survival and 1-year survival.

Impact of guideline-based medical therapy on malignant arrhythmias and mortality among heart failure patients implanted with a primary prevention ICD/CRTD

Abstract Funding Acknowledgements Type of funding sources: None. Background In contrast with the well-established impact of heart failure (HF) medical treatment reducing HF hospitalizations and improving survival, its impact on ventricular arrhythmia (VA) is based mainly on circumstantial evidence. Aim To evaluate prevalence of HF medical treatment and its impact on VA and overall survival among HF patients implanted with primary prevention ICD/CRTD. Methods Single center retrospective analysis of all HF patients implanted with ICD/CRTD as primary prevention. Patients" indication for implant according to guidelines was confirmed by a senior EP physician. Thereafter, the association of HF medications and dose (% guideline recommended target dose) of beta-blockers (BB), Angiotensin-antagonists (AgA), Mineralocorticoid-antagonsits (MRA), and Anti-Arrhythmic Drugs (AAD) with VA episodes and overall mortality was analyzed, based on patients" medical records and device clinic regular interrogations. Results 186 HF patients qualifying for primary prevention ICD/CRTD implant according to HF and device guidelines, were included. Their mean ± SD age 66.4 ± 12 years, 15.1% female, 79 (42.5%) implanted with an ICD and 107 (57.5%) with CRTD. During 3.8 [2.1;6.7] (median[IQR]) years; 52 (28%) had VA and 77 (41.4%) died. Treatment (medication, % of patients) included: BB (83%), AgA (87%), MRA (59%), and AAD (43.5%). Doses were 25[12.5;50]% of target for BB or AgA and 25[0;50]% of target for MRA. Treatment with &amp;gt;25% target dose of BB was associated with significantly reduced VA incidence. In a multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was significantly and independently associated with reduced VA (HR 0.443 95%CI 0.222-0.885; p = 0.021). Kapkan-Myer analysis for survival without VA according to each medication group dose, supported reduced VA among patients receiving &amp;gt; median dose of BB (Figure 1). Multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment; VA was associated with increased mortality (HR 2.672; 95% CI 1.429-4.999; p = 0.002) while AgA treatment was significantly and independently associated with reduced mortality (HR 0.515; 95% CI 0.285-0.929; p = 0.028). Conclusions In this cohort of real-life HF patients discharged after primary prevention ICD/CRTD implant, most of the patients were prescribed with guideline-based HF medications albeit with low doses. Higher BB dose was associated with reduced VA, while treatment with AgA was associated with improved survival. Abstract Figure. Survival without VA according to HF medi

Heart failure with improved ejection fraction in advanced heart failure clinic

Abstract Objectives The aims of the study were: (1) to determine the pattern of myocardial fibrosis assessed by delayed gadolinium enhancement cardiac MRI (DGE-CMRI) in patients with heart failure improved ejection fraction (HF-iEF) in an advanced heat failure clinic; and (2) to examine the dosage of beta-blocker and angiotensin converting enzyme inhibitor/ angiotensin receptor blockage/angiotensin neprilysin inhibitor (ACE-I/ARB/ARNI) in those patients. Methods HF-iEF was defined as patients with LVEF &amp;gt;40% with previously documented LVEF &amp;lt;35% at baseline. Results Among 312 consecutive patients with HF-rEF who were referred for an advanced HF clinic, 18% (56 patients) had HF-iEF within 12 months after referral. Of these, 84% (47 patients) had non-ischemic cardiomyopathy (CM); complete data on MRI for analysis were available for 25 of these patients (62%). Myocardial scar was found in 52% of patients with nonischemic CM (13 of 25). All patients with nonischemic CM had the myocardial scar of less than 10% of the total LV volume. Mid-wall DGE of the interventricular septum was the most common scar pattern. Among patients with HF-iEF, 36% (20 patients) were referred for heart transplant. Two patients with peripartum related and nonischemic etiologies were listed for heart transplant, and delisted 12 months after. No patient died during 1-year follow up. At 12 months, the mean LVEF change was +27±12%. Improvement of the LVEF to ≥50% occurred in 31 patients (55%). The percentage use of ACE-I/ARB/ARNI and beta-blocker was significantly increased, at 1-year-follow-up. Fourteen percent and 48% of patients achieved target dose of ACE-I/ARB/ARNI and beta-blocker, respectively. There was no significant association between myocardial scar pattern or extent and dosage of medical titration. Conclusions HF-iEF was present in 18% of patients with HF-rEF after 1-year follow-up in advanced heart failure clinic. Mid-wall DGE of the interventricular septum was the most common scar pattern in nonischemic HF-iEF. None of patients with nonischemic HF-iEF had myocardial scar &amp;gt;10% of the total LV volume. Improvement of LVEF to ≥50% occurred in approximately half of the study patients, and led to delisting patients from heart transplant waiting list. The majority of patients had recovery of the LVEF when the target dose of beta-blocker or ACE-I/ARB/ARNI had not been achieved during medical up-titration. Funding Acknowledgement Type of funding source: None

Utilization of Mineralocorticoid Receptor Antagonists in an Advanced Heart Failure and Transplant Program in The Middle East

Background Heart failure with reduced ejection fraction (HFrEF) outcomes are influenced by optimal guideline-directed medical therapy (GDMT). This includes target doses of mineralocorticoid receptor antagonists (MRA). The underuse and under-dosing of this particular class of GDMT have been reported before. Recent studies have also demonstrated that some of the perceived concerns, such as lowering systolic blood pressure (SBP) that might preclude utilization of MRA in HFrEF, may only be theoretical. This study aims to explore MRA utilization and associated factors in an advanced heart failure program at a quaternary care center in the Middle East- Gulf Region. Methods We conducted a retrospective electronic chart review of all HFrEF patients presenting to the outpatient clinic in our program and followed them for one year. The group of patients who achieved MRA target dose at the one-year visit were compared to those who did not reach this goal. Descriptive analysis was performed for patient characteristics and a logistic regression was specified to examine predictors of reaching MRA target dose. Results A total of 123 HFrEF patients were included in this study for a mean follow-up period of 363.8±31 days. Table 1 shows patient characteristics and GDMT use at baseline and at 1-year follow-up. While more patients were on target doses of beta blockers and ACE/ARB/ARNI at follow-up when compared to baseline (p-value <0.05), this finding did not extend to MRA therapy. Only baseline renal function and serum potassium but not SBP were associated with reaching the target dose of MRA at the 1-year follow-up (Table 2). A 14.9 % decrease in the odds of receiving a target dose of MRA was observed for each 0.1 mmol/L increase in baseline potassium. An eGFR of ≥60 mL/minute/per 1.73 m2 correlated with a 207% increase in odds of being on target dose MRA when compared to lower eGFR. Conclusion In our advanced heart failure and transplant program, renal function and serum potassium but not SBP are associated with the titration of MRA therapy. While such programs might have a better understanding of the correct utilization and associated outcomes with this class of medication, there still needs to be more adoption of this important therapy. Heart failure with reduced ejection fraction (HFrEF) outcomes are influenced by optimal guideline-directed medical therapy (GDMT). This includes target doses of mineralocorticoid receptor antagonists (MRA). The underuse and under-dosing of this particular class of GDMT have been reported before. Recent studies have also demonstrated that some of the perceived concerns, such as lowering systolic blood pressure (SBP) that might preclude utilization of MRA in HFrEF, may only be theoretical. This study aims to explore MRA utilization and associated factors in an advanced heart failure program at a quaternary care center in the Middle East- Gulf Region. We conducted a retrospective electronic chart review of all HFrEF patients presenting to the outpatient clinic in our program and followed them for one year. The group of patients who achieved MRA target dose at the one-year visit were compared to those who did not reach this goal. Descriptive analysis was performed for patient characteristics and a logistic regression was specified to examine predictors of reaching MRA target dose. A total of 123 HFrEF patients were included in this study for a mean follow-up period of 363.8±31 days. Table 1 shows patient characteristics and GDMT use at baseline and at 1-year follow-up. While more patients were on target doses of beta blockers and ACE/ARB/ARNI at follow-up when compared to baseline (p-value <0.05), this finding did not extend to MRA therapy. Only baseline renal function and serum potassium but not SBP were associated with reaching the target dose of MRA at the 1-year follow-up (Table 2). A 14.9 % decrease in the odds of receiving a target dose of MRA was observed for each 0.1 mmol/L increase in baseline potassium. An eGFR of ≥60 mL/minute/per 1.73 m2 correlated with a 207% increase in odds of being on target dose MRA when compared to lower eGFR. In our advanced heart failure and transplant program, renal function and serum potassium but not SBP are associated with the titration of MRA therapy. While such programs might have a better understanding of the correct utilization and associated outcomes with this class of medication, there still needs to be more adoption of this important therapy.

Guideline-Directed Therapy In An Elderly Homebound Population of Heart Failure Patients

Introduction Adherence to guideline-directed therapy in heart failure patients is an important goal. Traditionally, elderly patients have difficulties attaining target doses of these therapies and this may be exaggerated in a homebound population. Hypothesis We assessed the differences in use of Angiotensin-Converting Enzyme inhibitors (ACEis)/Angiotensin Receptor Blockers (ARBs) and Beta-Blockers (BBs) in homebound heart failure patients in 2 age groups (≥75 years old and Methods A total of 471 heart failure patients during January 2016-March 2020 were reviewed via electronic medical record (Refer to Table 1 for Characteristics). Homebound patients are characterized as those seen for medical visits at home or at a non-medical facility. Both groups were reviewed for the administration and dosage of ACEis/ARB and BBs. Due to the use of multiple ACEis and ARBs, daily doses were converted to a Lisinopril Equivalent Dose (LED) for a singular continuous variable for comparison. Similarly, beta-blocker daily dosages were converted to a Carvedilol Equivalent Dose (CED). Proportions of patients who reached target doses of Lisinopril (20-40 mg) and Carvedilol (25 mg BID) in both age groups were compared via t-test. Results Group 1 consisted of n=308 patients (65.4%). Group 2 consisted of n=163 patients (34.6%). Group 1 patients on ACEi/ARB and BB were 81.5% and 57.8%, respectively. Group 2 patients were on ACEi/ARB and BB at similar percentages (81.0% and 57.1%, respectively). Group 1 had a mean LED of 21.7±12.5 mg and a mean CED of 22.2±15.2 mg, with 49.0% reaching the target LED and 11.0% reaching the target CED. Group 2 had a mean LED of 23.2±12.5 mg and a mean CED of 24.5±17.6 mg, with 51.5% reaching the target LED and 12.9% reaching the target CED (Refer to Table 1). Both group means reached the target daily dose of Lisinopril (p=0.2440) but did not reach the minimum target daily dose of carvedilol (p=0.3087) (Refer to Figure 1). Conclusions Patients within both younger and older age demographics are able to reach similar daily doses of guideline-directed heart failure medication. Target doses of BBs were less frequently attained probably due to the frequent presence of numerous comorbidities.

Impact of Clinical Audit on Adherence to the Guidelines Directed Medical Therapy in Patients Admitted with Heart Failure.

The adoption of guideline recommendations of pharmacotherapy to improve the clinical course of Heart Failure (HF) remains below par. Our objective is to evaluate the impact of clinical audit on adherence to the Guideline-Directed Medical Therapy (GDMT) in patients admitted with acute heart failure with reduced ejection fraction (EF). A prospective interventional study was conducted over a period of 12 months from June 2018 to May 2019 in all patients admitted with acute heart failure with reduced ejection fraction. The discharge prescriptions of patients who met the inclusion criteria were audited for appropriateness in the usage of neurohormonal blockers and Ivabradine, by a clinical pharmacist on a monthly basis. Audit results were presented to the practicing physicians every month and feedback was given. Discharge prescriptions of 716 patients who presented with HF were audited for the reasonable or unreasonable omission of neurohormonal blocking drugs. The first-month audit revealed that the unreasonable omission of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers/ Angiotensin Receptor Neprilisin Inhibitors ( ACEI/ARB/ARNI), Betablockers and Mineralocorticoid Receptor Antagonists (MRA) were 24.5%, 13.1%, and 9.09% respectively, which reduced to nil at the end of the study period (p=0.00). Initiation of Ivabradine before prescribing or achieving the target dose of Betablocker was noted in 38.18% of patients in the first month, which was also reduced to nil (p=0.00) at the end of the study. This study reveals that periodic clinical audit improves adherence to GDMT in patients admitted with heart failure with reduced ejection fraction.

Management of Heart Failure with Reduced Ejection Fraction after ESC 2016 Heart Failure Guidelines: The Linx Registry.

AimsIn May 2016, a new version of the European Society of Cardiology (ESC) Guidelines for the management of heart failure (HF) was released. The aim of this study was to describe the management of HF with reduced ejection fraction after the publication of ESC Guidelines.Methods and resultsThe Linx registry is a multicentre, observational, cross‐sectional study from 14 Catalan hospitals that enrolled 1056 patients with HF and reduced left ventricular ejection fraction (≤40%) from 1 February to 30 April 2017 in outpatient cardiology clinics. Results were compared between hospitals according to their level of complexity in our own registry and compared with previously published registries similar to ours. Sacubitril/valsartan was prescribed to 23.9% of patients in our population, as a consequence, use of angiotensin‐converting enzyme inhibitor and angiotensin receptor blockers in monotherapy decreased to 48.1% and 16.9%, respectively, and prescription of beta‐blockers (91.8%), mineralocorticoid receptor antagonists (72.7%), and ivabradine (21.4%) remained similar to previous registries. Target doses of beta‐blockers (25.4%), angiotensin‐converting enzyme inhibitors (24.9%), angiotensin receptor blockers (7.7%), sacubitril/valsartan (8.1%), and mineralocorticoid receptor antagonists (19.7%) were accomplished in a low proportion of patients. Our results also suggest that prescription and up‐titration of class I HF drugs were greater in hospitals with higher level of complexity.ConclusionsThe Linx registry shows an appropriate adherence to pharmacological recommendations from ESC HF Guidelines despite a low proportion of patients reached target doses. Almost one‐quarter of patients were under treatment with sacubitril/valsartan a few months after ESC HF Guidelines recommendations.

Utilization of guideline-directed medical therapy in patients with de novo heart failure with reduced ejection fraction: A Veterans Affairs study.

Background:The utilization of guideline-directed medical therapy (GDMT) significantly reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Previous studies have documented the underutilization of GDMT in HFrEF. The present study aimed to determine reasons for underutilization and achievement of target doses of GDMT in patients with de novo diagnosis of HFrEF.Methods:Patients presenting with de novo HFrEF at the Veterans Affairs Medical Center were included. Baseline demographic, clinical, and echocardiographic data were collected. The utilization of target doses of GDMT was assessed at the time of discharge and 1-, 3-, 6-, and 12-month follow-up.Results:Of the 95 patients who met the criteria for de novo HFrEF, 48 were included in the final analysis. Dose titration of either beta-blocker or angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) was attempted in 20 patients (42%) at 1 month, 21 patients (44%) at 3 months, 13 patients (27%) at 6 months, and 14 patients (29%) at 12 months. Nine (19%) patients were on a target dose of beta-blockers and three (6%) patients were on a target dose of an ACEi/ARB at 12 months. The most common reasons for underutilization were patient-level factors, such as hypotension, acute kidney injury/hyperkalemia, and patient noncompliance.Conclusions:Utilization and achievement of target doses of GDMT were suboptimal among patients discharged with de novo HFrEF during a 1-year follow-up. Although patient factors may limit the up-titration of therapies, concerted efforts are needed to support primary care physicians in improving adherence to target doses of GDMT in patients with HFrEF.

Beta-blocker target dosing and tolerability in a dedicated heart failure clinic in Johannesburg.

Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.