HFrEF Patients Research Articles

Utility of PREDICT-HF score in high-risk Asian heart failure patients receiving sacubitril/valsartan.

ObjectiveThe aim of this study was to investigate the application of sacubitril/valsartan in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles.MethodsThe TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with sacubitril/valsartan were enrolled and categorized by: (1) high-risk group with ≥1 of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100 mmHg), and renal impairment (eGFR <30 ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model.ResultsA total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70–0.76) and 0.71 (95% CI 0.65–0.76), respectively. The permanent discontinuation rate among the high-risk patients was significantly higher than that among the standard-risk patients (8.3 vs. 2.5 per 100 patient-years, p < 0.001).ConclusionsReal-world outcomes of the TAROT-HF study demonstrated that the PREDICT-HF model performed well in Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating sacubitril/valsartan.

Levosimendan as a "Bridge to Optimization" in Patients with Advanced Heart Failure with Reduced Ejection-A Single-Center Study.

Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of β-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients.

Uric Acid Predicts Recovery of Left Ventricular Function and Adverse Events in Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses.

Background and AimsHeart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF.MethodsHFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016–2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF.ResultsAfter adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172–1.328); P < 0.001] of NIS dataset. In Xianyang prospective cohort study, hyperuricemia is a significant and independent risk factor for all-cause death (adjusted HR 2.387, 95% CI 1.141–4.993; P = 0.021), heart failure readmission (adjusted HR 1.848, 95% CI 1.048–3.259; P = 0.034), and composite events (adjusted HR 1.706, 95% CI 1.001–2.906; P = 0.049) in HFrEF patients. UA value at baseline was negatively correlated to LVEF of follow-ups (r = −0.19; P = 0.046). Cutoff UA value of 312.5 μmmol/L at baseline can work as a predictor of LVEF recovery during follow-up, with the sensitivity of 66.7%, the specificity of 35.1%, and the accuracy of 0.668 (95% CI, 0.561–0.775; P = 0.006). Moreover, gene overlap analysis and network proximity analysis demonstrated a strong correlation between HFrEF and Hyperuricemia.ConclusionLower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF.

Guideline-directed medical therapy in heart failure patients with reduced ejection fraction in Oman: utilization, reasons behind non-prescribing, and dose optimization

Background: Objective:To determine the reasons behind guideline-directed medical therapy (GDMT) non-prescribing, drug utilization before and after excluding those intolerable to GDMT, as well as dose optimization in heart failure (HF) patients with reduced ejection fraction (<40%) (HFrEF) in Oman.Methods:The study included HF patients seen at the medical outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January 2016 and December 2019 and followed up until the end of June 2021. The use of renin-angiotensin-system (RAS) blockers (angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs)), beta blockers and mineralocorticoid receptor antagonists (MRAs) were evaluated as per the European, American, and Canadian HF guidelines. Analyses were performed using univariate statistics.Results:A total of 171 HFrEF patients were enrolled for this study, the overall mean age of the cohort was 63 ± 15 years old and 59% were male. Over 65% of the patients had chronic kidney disease. Almost 55% of the patients were intolerable to GDMT. The proportion of patients on beta blockers, RAS blockers/ hydralazine-isosorbide dinitrate combination, and MRAs, before and after excluding those intolerable to GDMT, were 89%, 97%, and 77%, and, 94%, 47% and 85%, respectively, while the proportion of patients on the GDMT combination concomitantly was 41% and 83%, respectively. A total of 61%, 44% and 100% of the patients were prescribed ≥50% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively, while 19%, 8.2% and 94% of the patients attained 100% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively.Conclusions:Reasons behind GDMT non-prescribing were frequent and not clearly obvious in patients’ medical notes. The majority of the patients were prescribed GDMT. However, dose optimization, specifically for beta blockers and RAS blockers/ HYD-ISDN combination, was still suboptimal. The findings should be interpreted in the context of low study power and that future studies, with larger sample sizes, are warranted to minimize this limitation.

Prognostic value of 6-min walk test compared to cardiopulmonary exercise test in patients with severe heart failure.

The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are both predictive in heart failure (HFrEF). Although 6MWT substitutes for CPET in HFrEF patients, as submaximal testing may be preferable, its prognostic superiority still needs to be verified, particularly in regard to beta blockers (BBs). We aimed to compare the prognostic role of CPET and 6MWT and investigate whether BB therapy influences the predictive value. This is a single-center, retrospective study. Advanced HFrEF patients were followed up for 3 years: events were cardiovascular death or urgent heart transplantation. We analyzed the predictive capacity of CPET and 6MWT in patients, and subdivided according to use of BBs. In a group of 251 HFrEF patients, we found a correlation between meters and peak VO2 (r2 = 0.94). Over the 3-year follow-up, 74 events were recorded. Both CPET and 6MWT variables were correlated with outcome at univariate analysis (meter and VE/VCO2 slope, peak VO2, VO2 at ventilatory anaerobic threshold, percentage predicted of peak VO2), but only percentage predicted of peak VO2 (pppVO2) was an independent predictor. In 103 HFrEF patients on BBs (23 nonsurvivors), neither pppVO2 nor meter were predictive, while in 148 patients not treated with BB (51 with events) pppVO2 was selected as an independent prognostic parameter (P = 0.001). 6MWT is a valid alternative to CPET, although the percentage of predicted of peak VO2 emerged as the strongest predictor. Nonetheless, our results suggest that both functional derived parameters are not predictive among those patients treated with BBs. Further studies are necessary to confirm these findings.

EFFORT PERCEPTION AND HEMODYNAMIC RESPONSES TO THE 3/7 VS. 3X9 METHODS IN HEART FAILURE AND IN CORONARY ARTERY DISEASE PATIENTS: A RANDOMIZED-CROSS-OVER STUDY

Objective: Patient adherence to cardiac rehabilitation (CR) centers may be improved by shorter exercise time. The new ‘3/7-method’, which consists of 5 successive sets of exercise with an increasing number of repetitions (3 to 7) separated by brief inter-set rest intervals (15 s), has been proven to achieve a greater and faster strength gain in healthy subjects. Further characterization (i.e., Borg scale, blood pressure (BP) and heart rate (HR)) of the 3/7-method safety is needed before using it in CR in patients with reduced ejection fraction (HFrEF) and coronary artery disease (CAD). Design and method: Using a randomized and cross-over study design, we compared the variation of Borg scale, BP and HR in the ‘3/7-method’ vs ‘3X9 method’ (gold standard - .3 to 9 repetitions with a longer inter-set rest interval (1 min)) in 23 HFrEF (58 ± 9y-13% female) and 22 CAD patients (64 ± 10y-14% female). The strength training consisted in leg extension against a load of ~ 70% of 1 repetition maximal. Perceived exertion was assessed at the end of the last set by using the modified Borg Scale (0–10). HR and BP were assessed noninvasively beat by beat. Results: Baseline BP, HR and Borg scale at the end of exercise were similar within the two methods. HR was higher with the 3/7 method compared to the 3X9 method in the HFrEF (85 ± 11 vs. 83 ± 12 bpm,-p = 0.014) and CAD (90 ± 13 vs. 87 ± 14 bpm,-p = 0.03) patients. In the CAD patients, systolic BP increased more with the 3/7 method compared to the 3X9 method (143 ± 22 vs. 133 ± 20 mm Hg-(p &lt; 0.001)). Conclusions: The 3/7 and 3X9 strength training protocols elicit similar effort perception in our patients. The 3/7 method increases slightly HR in both groups and induces minimal rise in systolic BP in CAD patients. Taken together, our study suggests that, compared to the 3x9 method, the new 3/7-method is well tolerated and time-saving, at the price of small and likely irrelevant HR and BP variations. These encouraging results warrants further investigation of the advantages (i.e, adherence, improve strength and exercise capacity) of the 3/7 method in CR.

Head-to-head comparison between recommendations by the ESC and ACC/AHA/HFSA heart failure guidelines.

Recommendations represent the core messages of guidelines, and are particularly important when the body of scientific evidence is rapidly growing, as in the case of heart failure (HF). The main messages from two latest major HF guidelines, endorsed by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA), are partially overlapping, starting from the four pillars of treatment for HF with reduced ejection fraction. Some notable differences exist, in part related to the timing of recent publications (most notably, the Universal Definition of HF paper and the EMPEROR-Preserved trial), and in part reflecting differing views of the natural history of HF (with a clear differentiation between stages A and B HF in the ACC/AHA/HFSA guidelines). Different approaches are proposed to specific issues such as risk stratification and implantable cardioverter defibrillator use for primary prevention in HFrEF patients with non-ischaemic aetiology. The ACC/AHA/HFSA guidelines put a greater emphasis on some issues that are particularly relevant to the US setting, such as the cost-effectiveness of therapies and the impact of health disparities on HF care. A comparison between guideline recommendations may give readers a deeper understanding of the ESC and ACC/AHA/HFSA guidelines, and help them apply sensible approaches to their own practice, wherever that may be in the world. A comparison may possibly also help further harmonization of recommendations between future guidelines, by identifying why some areas have led to conflicting recommendation, even when ostensibly reviewing the same published evidence.

Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker.

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.

C23 HOW TO IMPROVE ADHERENCE TO ESC HF GUIDELINES THE PONTE (PDTA FOR INTEGRATED FOLLOW–UP TERRITORY HOSPITAL OF THE PATIENT WITH CARDIAC HEART FAILURE) PROJECT

Abstract Background A careful and integrated follow up after hospitalization for heart failure (HF) may represent a feasible strategy to optimize the adherence to ESC guidelines and reduce the occurrence of adverse events (mortality, re–hospitalizations). Methods A strict integration between hospital and local health district proximity office cardiologist through an integrated clinical data sharing software has been implemented in Apulia region, Italy, in order to optimize the management of the HF patient after an hospitalization: the PONTE (PDTA FOR INTEGRATED FOLLOW–UP TERRITORY HOSPITAL OF THE PATIENT WITH CARDIAC HEART FAILURE) (bridge) project. As until December 2021, 1200 patients with HF have been enrolled in the project, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). Adherence to ESC HF guidelines in HFrEF patients before vs after December 2020 was compared. Results In the HFrEF population (56%) the mean age was 63 years, 38% were hypertensive, 15% diabetic, 40% had ischemic heart disease, 42% were previously treated with coronary angioplasty, 56% had an ICD/CRT, 22% had atrial fibrillation. Mean NYHA class was 2.2, mean LVEF 30%, mean NT–proBNP values 4027 pg/mL, mean serum creatinine 1 mg/dL, 91% were taking beta–blockers (BB), 86% mineral corticoid receptor antagonists (MRA), 98% ACE–inhibitors/angiotensin–receptor–antagonists/neprilysin and angiotensin receptor antagonists (ACE/ARB/ARNI), and 13% ARNI. Compared to patients enrolled before 2020, ARNI prescription increased in 2021 (60% vs 13%, p &amp;lt; 0.001); in 30% ARNI were prescribed in hospital before discharge. Furthermore, in 10% of the population (most diabetics), sodium glucose cotransporter type 2 inhibitors (SGLT2i) have been prescribed as indicated by the latest ESC 2021 guidelines. Conclusions The implementation the PONTE project shows an improved adherence to ESC HF guidelines.

P239 TOLERABILITY OF SACUBITRIL/VALSARTAN TREATMENT IN OLDER PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION: PRELIMINARY DATA FROM THE REAL–WORLD AGING–HF REGISTRY

Abstract Background Although older patients with heart failure (HF) with reduced ejection fraction enrolled in PARADIGM–HF showed a good tolerance to sacubitril/valsartan (Sa/Va), more real–word data are needed to define their tolerability in this population. Aim: To describe the Sa/Va tolerability and titration in older HFrEF patients followed by our HF outpatient. Methods HFrEF patients aged ≥65 years and treated with Sa/Va from November 2016 to June 2021 were enrolled, assessing Sa/Va tolerability at six months and its clinical and hemodynamic effects. Results We enrolled 101 patients with a mean age of 78 years (⁓20% female). The aetiology was ischemic in 59% of cases while the mean ejection fraction was 31%. Sa/Va was prescribed at the starting dose (24/26mg) and intermediate dose (49/51mg) in 91% and 9% of cases, respectively. After six months, 9 of the 100 patients still alive had discontinued treatment with Sa/Va (4 for symptomatic hypotension, 3 for suspected allergic reaction and 2 for worsening renal function). Of the 91 patients still on therapy, only 17 had reached the target dose (97/103mg) while 28 were at the intermediate dose (Figure 1). Symptomatic hypotension (62%), hyperkalaemia (15%) and worsening of renal function (4%) were the main causes of maintaining Sa/Va therapy at the starting dose; note, in 15% of cases a specific cause of non–titration was not identified. Comparing HF treatment between starting dose vs higher–dose patients, after six months in low–dose patients there was a slight improvement in mineralcorticosteroid receptor antagonist (MRA) prescription and in combination therapy (Sa/Va, beta–blocker and MRA) while in patients at higher–doses there was a significant decrease (Figure 2). In patients still receiving Sa/Va, significant clinical improvement was observed while renal function, K+ levels and systolic blood pressure remained stable (Figure 3). Conclusions After six months of treatment, Sa/Va was well tolerated in most of our older patients and used in combination with a beta–blocker and an MRA in a high percentage of cases, although a reduction in MRA prescription is observed in patients taking higher dosages of Sa/Va. In addition, there was a marked improvement in the clinical variables.

Prediabetes and insulin resistance in a population of patients with heart failure and reduced or preserved ejection fraction but without diabetes, overweight or hypertension

BackgroundThe relationships between glucose abnormalities, insulin resistance (IR) and heart failure (HF) are unclear, especially regarding to the HF type, i.e., HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Overweight, diabetes and hypertension are potential contributors to IR in persons with HF. This study aimed to evaluate the prevalence of prediabetes and IR in a population of Vietnamese patients with HFrEF or HFpEF but no overweight, diabetes or hypertension, in comparison with healthy controls, and the relation between prediabetes or IR and HF severity.MethodsWe conducted a prospective cross-sectional observational study in 190 non-overweight normotensive HF patients (114 with HFrEF and 76 with HFpEF, 92.6% were ischemic HF, mean age was 70.1 years, mean BMI 19.7 kg/m2) without diabetes (neither known diabetes nor newly diagnosed by OGTT) and 95 healthy individuals (controls). Prediabetes was defined using 2006 WHO criteria. Glucose and insulin levels were measured fasting and 2 h after glucose challenge. IR was assessed using HOMA-IR and several other indexes.ResultsCompared to controls, HF patients had a higher prevalence of prediabetes (63.2% vs 22.1%) and IR (according to HOMA-IR, 55.3% vs 26.3%), higher HOMA-IR, insulin/glucose ratio after glucose and FIRI, and lower ISIT0 and ISIT120 (< 0.0001 for all comparisons), with no difference for body weight, waist circumference, blood pressure and lipid parameters. Prediabetes was more prevalent (69.3% vs 53.9%, p = 0.03) and HOMA-IR was higher (p < 0.0001) in patients with HFrEF than with HFpEF. Among both HFrEF and HFpEF patients, those with prediabetes or IR had a more severe HF (higher NYHA functional class and NT-proBNP levels, lower ejection fraction; p = 0.04–< 0.0001) than their normoglycemic or non-insulinresistant counterparts, with no difference for blood pressure and lipid parameters.ConclusionIn non-diabetic non-overweight normotensive patients with HF, the prevalence of prediabetes is higher with some trend to more severe IR in those with HFrEF than in those with HFpEF. Both prediabetes and IR are associated with a more severe HF. The present data support HF as a culprit for IR. Intervention strategies should be proposed to HF patients with prediabetes aiming to reduce the risk of incident diabetes. Studies should be designed to test whether such strategies may translate into an improvement of further HF-related outcomes.

Benefits of cardiac rehabilitation in cardio-renal patients: a retrospective study of heart failure 578 patients with reduced ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Chronic kidney disease (CKD) is common during the course of heart failure (HF). It is often associated with worse prognosis and complicates the management of these patients. Moreover CKD is accompanied by sarcopenia, which may limit the benefits of cardiac rehabilitation (CR) in the cardio-renal syndrome (CRS). The aim of this study was to evaluate the effect of CR on the physical capacities according to the stage of CKD assessed by a cardiorespiratory exercise test (CPET) at the beginning and end of the program in patients with reduced ejection fraction (HFrEF). Methods This is a retrospective study, conducted from January 2004 to December 2019 on 573 consecutive HFrEF patients, who benefited from a 4-week CR. Patients were divided into 4 groups according to their GFR (group (G) 1 &amp;gt;= 60; G2: 45-59; G3: 30-44; G4 &amp;lt; 30 ml/min/1.73m². We compared these groups (ANOVA test) and looked with multivariate analysis for factors associated with an improvement in peak VO2 (VO2p). Results Of the general population, 38% of patients had a GFR&amp;lt;60ml/min. After CR, there was an improvement in VO2p (15.4 vs 17.8, p=0.00009), SV1 (10.5 vs12.4, p=0.0001), watts (77 vs 93.6, p&amp;lt;0.000), and BNP (688 vs 488, p=0.00002). With decreasing stages of CKD, there was a deterioration in VO2p (16.2, 14.3, 13.6, 13.3), SV1 (10.9, 10.1, 9.3, 9.1), watts (83.4, 69.2, 66.3, 55.2), and an increase BNP levels (570, 885, 771, 1235 pg/ml). The improvement in VO2p, SV1, watts, BNP was statistically significant for all stages of CKD except in group 4 for VO2p (13.3 vs 14.4, p=0.1). In multivariate analysis factors predicting improvement in VO2p were baseline VO2p and maximal systolic blood pressure. Conclusion CR is beneficial in HFrEF patients with CKD. CRS should not be a barrier to prescribing CR.

Effort perception and hemodynamic responses to the 3/7 vs. 3X9 methods in heart failure and in coronary artery disease patients: a randomized-cross-over study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fonds Erasme pour la recherche médicale Background/Introduction The hemodynamic response to strength training depends on the intensity, the time of rest between exercise sets and the duration of the exercise (1-3). A new method (the ‘3/7 method’), which consist of 5 successive sets of exercise with an increasing number of repetitions (3 to 7) separated by brief inter-set rest intervals (15 s), achieved a greater and faster strength gain after 12 weeks of training in young healthy subjects (4-5) (Fig 1). Further characterization of the tolerability of 3/7 method, as well as rise in blood pressure (BP) and heart rate (HR) it may induce, is needed in a patient population before this methodology can be applied in cardiac rehabilitation centers (6). These parameters were compared to those induced by 3 series of 9 repetitions (‘3X9 method’) with a longer inter-set rest interval (1min), using a randomized and cross-over study design. Purpose This study investigated the Borg scale and hemodynamic response of the 3/7 vs. 3X9 strength training methods in heart failure patients with reduced ejection fraction (HFrEF, Left ventricular ejection fraction (LVEF) &amp;lt; 40%) and patients with coronary artery disease (LVEF&amp;gt; 40%, CAD). Method 23 HFrEF (58±9 y, 13% female) and 22 CAD (64±10 y, 14% female) participated in the study. CAD underwent revascularization between 1 and 6 months prior to the study. Patients with decompensated heart failure, atrial fibrillation, major orthopedics disabilities were not included in the study. The strength training consisted in leg extension against a load of ~ 70% of 1 repetition maximal (1RM). Perceived exertion was also assessed at the end of the last set by using the modified Borg Scale (0-10). HR and BP were assessed noninvasively beat by beat (Task Force Monitor). We compared baseline and peak exercise values in each group. All participants signed an agreement form approved by the local Ethic Review Board. Result Baseline BP and HR and effort perception at the end of exercise did not differ between the 3/7 and 3X9 groups (Borg scale: HFrEF 3/7 method: 5,4±2,6 vs. 3X9 method: 5,8±2,5; CAD 3/7 method: 6,2±1,3 vs. 3X9 method: 6,1±1,5; p= NS) (Fig 2). HR became faster with the 3/7 method as compared to the 3X9 method in the HFrEF (85±11 vs. 83±12 bpm, p=0.014, respectively) and CAD (90±13 vs. 87±14 bpm, p=0.03, respectively) patients. In the CAD group, systolic BP increased more with the 3/7 method than with the 3X9 method (143±22 vs. 133±20 mm Hg, p&amp;lt;0.001). Other parameters did not differ. Conclusion The 3/7 and 3X9 strength training protocols elicit comparable effort perception and similar hemodynamic responses in HFrEF and CAD. The 3/7 method increases transiently HR by a few more beats in both groups and raises systolic BP by 10 additional mmHg in CAD patients. Taken together, this study suggests the 3/7 method is safe in patients with HFrEF and CAD, and warrants further investigation of the usefulness of the 3/7 method in cardiac rehabilitation units.

20 Years of Real-World Data to Estimate the Prevalence of Heart Failure and Its Subtypes in an Unselected Population of Integrated Care Units.

Introduction: Heart failure (HF) is a clinical syndrome caused by structural and functional cardiac abnormalities resulting in the impairment of cardiac function, entailing significant mortality. The prevalence of HF has reached epidemic proportions in the last few decades, mainly in the elderly, but recent evidence suggests that its epidemiology may be changing. Objective: Our objective was to estimate the prevalence of HF and its subtypes, and to characterize HF in a population of integrated care users. Material and Methods: A non-interventional cross-sectional study was performed in a healthcare center that provides primary, secondary and tertiary health cares. Echocardiographic parameters (left ventricle ejection fraction (LVEF) and evidence of structural heart disease) and elevated levels of natriuretic peptides were used to define two HF phenotypes: (i) HF with a reduced ejection fraction (HFrEF, LVEF ≤ 40% and either NT-proBNP ≥ 400 pg/mL (≥600 pg/mL if atrial fibrillation (AF)/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter)) and (ii) HF with a non-reduced ejection fraction (HFnrEF), which encompasses both HFpEF (LVEF ≥ 50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality) and HF with a mildly reduced fraction (HFmrEF, LVEF within 40–50% and either NT-proBNP ≥ 200 pg/mL (≥600 pg/mL if AF/flutter) or BNP ≥ 100 pg/mL (≥125 pg/mL if AF/flutter) in the presence of at least one structural cardiac abnormality). The significance threshold was set at p ≤ 0.001. Results: We analyzed 126,636 patients with a mean age of 52.2 (SD = 18.3) years, with 57% (n = 72,290) being female. The prevalence of HF was 2.1% (n = 2700). The HF patients’ mean age was 74.0 (SD = 12.1) years, and 51.6% (n = 1394) were female. Regarding HF subtypes, HFpEF accounted for 65.4% (n = 1765); 16.1% (n = 434) had HFmrEF and 16.3% (n = 439) had HFrEF. The patients with HFrEF were younger (p < 0.001) and had a history of myocardial infarction more frequently (p < 0.001) compared to HFnrEF, with no other significant differences between the HF groups. The HFrEF patients were more frequently prescribed CV medications than HFnrEF patients. Type 2 Diabetes Mellitus (T2D) was present in 44.7% (n = 1207) of the HF patients. CKD was more frequently present in T2D vs. non-T2D HF patients at every stage (p < 0.001), as well as stroke, peripheral artery disease, and microvascular disease (p < 0.001). Conclusions: In this cohort, considering a contemporary definition, the prevalence of HF was 2.1%. HFrEF accounted for 16.3% of the cases, with a similar clinical–epidemiological profile having been previously reported in the literature. Our study revealed a high prevalence of patients with HFpEF (65.4%), raising awareness for the increasing prevalence of this entity in cardiology practice. These results may guide local and national health policies and strategies for HF diagnosis and management.

Effects of diabetes mellitus on left ventricular function and remodeling in hypertensive patients with heart failure with reduced ejection fraction: assessment with 3.0T MRI feature tracking.

BackgroundHeart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear.MethodsA total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM−]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses.ResultsDespite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM−) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM−) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [β = − 0.189; p = 0.011], GCPS [β = 0.217; p = 0.005], GLPS [β = 0.237; p = 0.002]). HTN was associated with impaired GLPS (β = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05).ConclusionsDM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.

Patient characteristics, short-term and long-term outcomes after incident heart failure admissions in a regional Australian setting

AimsThis study aims to (1) define the characteristics of patients with a first admission for heart failure (HF), stratified by type (reduced (HFrEF) vs preserved (HFpEF) ejection fraction) in a...

Ventricular longitudinal function by cardiovascular magnetic resonance predicts cardiovascular morbidity in HFrEF patients.

AimsVentricular longitudinal function measured as basal‐apical atrioventricular plane displacement (AVPD) or global longitudinal strain (GLS) is a potent predictor of mortality and could potentially be a predictor of heart failure‐associated morbidity. We hypothesized that low AVPD and GLS are associated with the combined endpoint of cardiovascular mortality and heart failure‐associated morbidity.Methods and resultsTwo hundred eighty‐seven patients (age 62 ± 12 years, 78% male) with heart failure with reduced (≤40%) ejection fraction (HFrEF) referred to a cardiovascular magnetic resonance exam were included. Ventricular longitudinal function, ventricular volume, and myocardial fibrosis or infarction were analysed from cine and late gadolinium enhancement images. National registries provided data on causes of cardiovascular hospitalizations and cardiovascular mortality for the combined endpoint. Time‐to‐event analysis capable of including reoccurring events was employed with a 5‐year follow‐up. HFrEF patients had EF 26.5 ± 8.0%, AVPD 7.8 ± 2.4 mm, and GLS −7.5 ± 3.0%. In contrast, ventricular longitudinal function was approximately twice as large in an age‐matched control group (AVPD 15.3 ± 1.6 mm; GLS −20.6 ± 2.0%; P < 0.001 for both). There were 578 events in total, and the majority were HF hospitalizations (n = 418). Other major events were revascularizations (n = 64), cardiovascular deaths (n = 40), and myocardial infarctions (n = 21). One hundred fifty‐five (54%) patients experienced at least one event (mean 2.0, range 0–64). Of these patients, 119 (71%) had three events or fewer, and the first three events comprised 51% of all events (295 events). Patients in the bottom AVPD or GLS tertile (<6.8 mm or >−6.1%) overall experienced more than 3 times as many events as the top tertile (>8.8 mm or <−8.4%; P < 0.001). Patients in this tertile also faced more cardiovascular deaths (P < 0.05), HF hospitalizations (P = 0.001), myocardial infarctions (only GLS: P = 0.032), and accumulated longer in‐hospital length‐of‐stay overall (AVPD 20.9 vs. 9.1 days; GLS 22.4 vs. 6.5 days; P = 0.001 for both), and from HF hospitalizations (AVPD 19.3 vs. 8.3 days; GLS 19.3 vs. 5.4 days; P = 0.001 for both). In multivariate analysis adjusted for significant covariates, AVPD and GLS remained independent predictors of events (hazard ratio 1.12 per‐mm‐decrease and 1.13 per‐%‐increase) alongside hyponatremia (<135 mmol/L), aetiology of HF, and LV end‐diastolic volume index.ConclusionsLow ventricular longitudinal function is associated with an increase in number of events as well as longer in‐hospital stay from cardiovascular causes. In addition, AVPD and GLS have independent prognostic value for cardiovascular mortality and morbidity in HFrEF patients.

A Retrospective Cohort Evaluation of a Pharmacist-Led Approach for Transitioning Patients to an Angiotensin Receptor—Neprilysin Inhibitor

Background: Heart failure guidelines recommend replacing an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) with an angiotensin receptor neprilysin inhibitor (ARNI) to reduce morbidity and mortality in NYHA Class II–III patients with reduced ejection fraction (HFrEF). Objective: This study aims to determine if a pharmacist-led outpatient ARNI replacement and titration program led to more patients achieving target doses of ARNI compared to usual care. Methods: A single health system, retrospective electronic medical record review identified 791 patients with active ARNI prescriptions and at least two outpatient cardiology visits with a pharmacist or usual care provider between January 2015 through September 2018. The primary outcome was the percentage of patients who achieved a target ARNI dose of 97/103 mg twice daily. The secondary outcomes were the median dose achieved, number of visits required to achieve target dose, hospitalizations, and all-cause death. Results: ARNI was initiated and continued by a pharmacist in 64 patients and 727 by usual care. More patients in the pharmacist group, 60.9% (n = 39), achieved target dose vs. 18.0% (n = 131) of patients managed by usual care (95% CI, 0.31–0.55, p < 0.0001). The pharmacist group also had higher median total daily dose of ARNI (200 mg (IQR = 300) vs 100 mg (IQR = 100), p < 0.0001) and more likely to achieve a higher total daily dose in fewer visits. Conclusions: An advanced practice provider pharmacist-led outpatient ARNI replacement and titration program was more effective in achieving target doses of ARNI in HFrEF patients as compared to usual care.

Effects of Sacubitril-Valsartan on Clinical, Echocardiographic, and Polygraphic Parameters in Patients Affected by Heart Failure With Reduced Ejection Fraction and Sleep Apnea.

BackgroundHeart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.MethodsWe recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 h before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.ResultsAfter 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine, and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p < 0.0001), central AHI (p < 0.0001), obstructive AHI (p < 0.0001), oxygen desaturation index (ODI) (p < 0.0001), and percentage time of saturation below 90% (TC90) (p < 0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP, and tricuspid annular plane excursion (TAPSE) contributed to 23.6, 7.6, 7.3, and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.ConclusionsOur results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.

Cardiovascular Outcomes Of Patients With Heart Failure Referred To Home Based Cardiac Rehabilitation

Introduction Heart Failure (HF) patients have significant morbidity, mortality and re-hospitalizations. Home-Based cardiac rehabilitation (HBCR) can provide ideal opportunity for patients with HF to reduce hospitalizations and death. Cardiovascular outcomes in HF patients who was referred to HBCR is not known. Methods Retrospective study of 188 patients with HF (heart failure with reduced ejection fraction [HFrEF] & heart failure with preserved ejection fraction [HFpEF]) referred to HBCR at Providence VA Medical Center after IRB approval. We compared outcomes of HF patients who attended HBCR vs patients did not attend HBCR (Non-HBCR) from 3 to 12 months. HBCR consisted of face-to-face entry & exit exam, weekly phone calls and exercise prescription adjustment for 12-weeks. Primary outcome was composite of all-cause mortality and cardiovascular hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: age, smoking, PCI and CABG status. In subgroup analysis, we compared HFrEF and HFpEF patients who have completed HBCR and compared outcome differences (weight, blood pressure, cholesterol, LDL, HDL, triglycerides, HbA1C, 6 Minutes walking test [6MWT], duke score and PHQ-9) pre and post-HBCR. Results From November 2017 to March 2020, 188 patients (mean age: 73, 98% Male) were referred to HBCR and 11 patients were excluded for the main analysis as their outcomes occurred in less than 90 days. 105/177 (59%) patients attended HBCR while 72/177 (41%) patients did not attend HBCR and 93/105 (89%) patients have completed HBCR. The primary outcome occurred in 14 patients (13.3%) in HBCR group and 19 patients (26.4%) in Non-HBCR group (adjusted HR=0.32, CI 0.15-0.68). There was no difference in cardiovascular hospitalization among two groups, however patients in HBCR group have lower all-cause hospitalizations and all-cause death, separately, between the two groups at 12 months. After HBCR completion, all outcomes (weight, blood pressure, cholesterol, LDL, HDL, triglycerides, HbA1C, 6MWT, duke score and PHQ-9) have improved in HFrEF and HFpEF group. Conclusion Completion of HBCR among HF patients was associated with a lower risk of long-term cardiovascular outcomes. HFrEF and HFpEF patients have same degree of improvement after HBCR when compared with each other. Heart Failure (HF) patients have significant morbidity, mortality and re-hospitalizations. Home-Based cardiac rehabilitation (HBCR) can provide ideal opportunity for patients with HF to reduce hospitalizations and death. Cardiovascular outcomes in HF patients who was referred to HBCR is not known. Retrospective study of 188 patients with HF (heart failure with reduced ejection fraction [HFrEF] & heart failure with preserved ejection fraction [HFpEF]) referred to HBCR at Providence VA Medical Center after IRB approval. We compared outcomes of HF patients who attended HBCR vs patients did not attend HBCR (Non-HBCR) from 3 to 12 months. HBCR consisted of face-to-face entry & exit exam, weekly phone calls and exercise prescription adjustment for 12-weeks. Primary outcome was composite of all-cause mortality and cardiovascular hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: age, smoking, PCI and CABG status. In subgroup analysis, we compared HFrEF and HFpEF patients who have completed HBCR and compared outcome differences (weight, blood pressure, cholesterol, LDL, HDL, triglycerides, HbA1C, 6 Minutes walking test [6MWT], duke score and PHQ-9) pre and post-HBCR. From November 2017 to March 2020, 188 patients (mean age: 73, 98% Male) were referred to HBCR and 11 patients were excluded for the main analysis as their outcomes occurred in less than 90 days. 105/177 (59%) patients attended HBCR while 72/177 (41%) patients did not attend HBCR and 93/105 (89%) patients have completed HBCR. The primary outcome occurred in 14 patients (13.3%) in HBCR group and 19 patients (26.4%) in Non-HBCR group (adjusted HR=0.32, CI 0.15-0.68). There was no difference in cardiovascular hospitalization among two groups, however patients in HBCR group have lower all-cause hospitalizations and all-cause death, separately, between the two groups at 12 months. After HBCR completion, all outcomes (weight, blood pressure, cholesterol, LDL, HDL, triglycerides, HbA1C, 6MWT, duke score and PHQ-9) have improved in HFrEF and HFpEF group. Completion of HBCR among HF patients was associated with a lower risk of long-term cardiovascular outcomes. HFrEF and HFpEF patients have same degree of improvement after HBCR when compared with each other.