Heart Failure Patients With Preserved Ejection Fraction Patients Research Articles

Chronopharmacokinetic and Metabolites Investigations of the Cardiovascular Drugs Perindopril

The heart and vascular systems are well-coordinated. There is a noticeable uneven distribution of regulatory mechanisms and pathogenic events over the course of a day. In addition, the physiological circadian clock of the cardiovascular system might be disrupted by several disorders. In terms of global mortality and morbidity, heart failure (HF) ranks high. The angiotensin receptor-neprilysin inhibitor perindopril is now a valid option for treating heart failure. There is a lack of comprehensive evaluations of perindopril’s safety and effectiveness in HF at the present time. First, we provided an overview of perindopril’s pharmacological actions, which include inhibiting the renin-angiotensin system and decreasing natriuretic peptide breakdown in the natriuretic peptide system. After that, we summed up the benefits of perindopril for heart failure patients with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), such as lowering the risk of death and hospitalization, reversing cardiac remodeling, regulating biomarkers of heart failure, improving quality of life, providing antiarrhythmic effects, enhancing renal dysfunction, and regulating metabolism. Our discussion of perindopril’s safety and tolerability in treating HFrEF or HFpEF came to a close. Although there is a considerable risk of hypotension, perindopril demonstrated superior safety and tolerability when compared with placebo. For HFrEF patients, perindopril is a safe and effective therapy option, however, for HFpEF patients, it shows little benefit, according to the majority of studies. Soon, perindopril will likely be one of the most effective drugs available to treat heart failure.

Prognostic implications of left ventricular ejection fraction trajectory changes in heart failure.

The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.

Left atrial mechanics and functional capacity in HFpEF patients with paroxysmal atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Exercise capacity and ventilatory efficiency are often impaired in heart failure patients with preserved ejection fraction (HFpEF). Since left atrial (LA) pressure, particularly during exercise plays a major role in the exercise intolerance observed in these patients, we aimed to characterize the contribution of resting LA mechanical properties, assessed by two-dimensional speckle tracking echocardiography upon exercise capacity. Objective To evaluate relationship between LA mechanics, measured by LA strain (LAS) and parameters of exercise capacity, assessed by cardiopulmonary exercise testing (CPET) in HFpEF patients with dyspnea and paroxysmal atrial fibrillation (AF). Methods The study included 23 consecutive patients (63 ± 8 years, 83 % males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), referred for elective pulmonary vein ablation. The probability of HFpEF was estimated using H2FPEF score. During sinus rhythm, all patients underwent speckle tracking echocardiography and cardiopulmonary exercise testing by treadmill. Peak oxygen uptake (VO2max) served as measure of functional capacity and ventilation/carbon dioxide output (VE/VCO2) slope as surrogate of ventilation/perfusion mismatch. Results Out of all the echocardiographic indices, only LA contractile strain and strain rate showed significant correlation with peak VO2 (both p < 0.05). All three strain components of LA phasic function, i.e. reservoir, conduit and contractile LAS, had significant relationship with VE/VCO2 slope (all p<0.050). Patients with LA strain rate above the median had significantly higher VE/VCO2 slope (p=0.025) and lower peak VO2 (p=0.010). In contrast, no correlations were observed between exercise parameters and LA volumes or LA emptying fraction or any other echocardiographic indices. Conclusions In HFpEF patients, VO2 max and VE/VCO2 slope are closely related to LA contractile strain, suggesting that abnormalities in LA mechanics may contribute to the blunted exercise capacity observed. Therefore, these markers can be used as an echocardiographic surrogate of functional capacity in HFpEF patients with paroxysmal AF.

Association Between Visceral Fat, Blood Pressure and Arterial Stiffness in Patients with HFpEF: A Mediation Analysis.

To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP). This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP. About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62-4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51-4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI -0.41-2.14). The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.

A retrospective study on the clinical significance of cardiac computed tomography in heart failure patients with preserved ejection fraction.

This study investigated the correlation between cardiac function parameters by cardiac computed tomography (CT) and the clinical outcomes of heart failure patients with preserved ejection fraction (HFpEF) to provide experimental data for the diagnosis of HFpEF. A total of 157 HFpEF patients admitted to our hospital from January 2017 to January 2019 were retrospectively analyzed. The patients were divided into event and non-event groups according to the occurrence or absence of adverse events. Cardiac function parameters, such as the left ventricular (LV) end-diastolic volume (LVEDV) and LV end-diastolic volume index (LVEDVI), were obtained via CT scan. Also, the N-terminal-pro hormone b-type natriuretic peptide (NT-proBNP) levels in patients' serum were measured using an enzyme linked immunosorbent assay (ELISA) kit, and echocardiographic parameters such as LV posterior wall thickness (LVPWT) were also recorded. Further, Cox regression was employed to analyze factors associated with the clinical outcomes. Compared with patients in the non-event group, the left ventricular end-diastolic mass (LVM), LVEDVI, left ventricular end-systolic volume index (LVESVI), left atrial end-diastolic volume index (LAEDVI), and left atrial end-systolic volume index (LAESVI) were significantly increased, and the left ventricular total emptying fraction (LVTEF) and left atrial total emptying fraction (LATEF) were markedly decreased in the event group patients. Also, the E/e' and LAEDVI were related factors affecting the clinical outcomes of HFpEF patients. The above indicators displayed a significant predictive for the clinical outcomes of HFpEF patients. Several cardiac function measures, including LAEDVI, are factors associated with the clinical outcomes of HFpEF patients.

Heart failure with preserved ejection fraction: Calculating the risk of future heart failure events and death.

We sought to develop a clinical model to identify heart failure patients with preserved ejection fraction (HFpEF) at highest risk for acute HF events or death. Between 2010 and 2019, 422 patients with HFpEF were followed. Acute HF events occurred in 190 patients (45%), including 110 (58%) with recurrent hospitalizations. Those with recurrent events had worse 6-min walk test (p < 0.001), higher brain N-terminal prohormone natriuretic peptide (NT-proBNP, p < 0.001), and higher New York Heart Association functional class (NYHA, p < 0.001). Overall survival rates in patients with 1 HF event vs > 1 HF events were: at 1-year 91.6 vs. 91.8%, at 3-years 84.7 vs. 68.3% and at 5-years 67.4 vs. 42.7%, respectively (p < 0.04). The Hfpef survivAL hOspitalization (HALO) score revealed best predictive capability for all-cause mortality combining the variables age (p = 0.08), BMI (p = 0.124), NYHA class (p = 0.004), need for diuretic therapy (p = 0.06), left atrial volume index (p = 0.048), systolic pulmonary artery pressure (p = 0.013), NT-proBNP (p = 0.076), and number of prior hospitalizations (p = 0.006). HALO score predicted future HF hospitalizations in an ordinal logistic regression model (OR 3.24, 95% CI: 2.45-4.37, p < 0.001). The score performance was externally validated in 75 HFpEF patients, confirming a strong survival prediction (HR 2.13, 95% CI: 1.30-3.47, p = 0.002). We developed a model to identify HFpEF patients at increased risk of death and HF hospitalization. NYHA class and recurrent HF hospitalizations were the strongest drivers of outcome.

Spironolactone Utilization among Patients with Reduced and Preserved Ejection Fraction Heart Failure

Background: Spironolactone is a mineralocorticoid receptor antagonist indicated for the management of heart failure with reduced ejection fraction (HFrEF). In a previous clinical trial, spironolactone significantly lowered the incidence of heart failure (HF) hospitalizations among HF patients with preserved ejection fraction (HFpEF). Real world utilization of spironolactone in HFrEF and HFpEF is unknown. Methods: We conducted a retrospective cohort study using data from FDA’s Sentinel System. We identified patients with HFrEF or HFpEF using diagnosis and procedure codes from a previously validated algorithm. We required patients to be continuously enrolled in the 183 days prior to HF diagnosis. Follow-up started on the day of HF diagnosis and ended at the earliest occurrence of a spironolactone dispensing, disenrollment, death, or end of data. We calculated the proportion of spironolactone utilization, and for those initiating treatment, we estimated the dose and duration of the first continuous treatment episode. Results: Among 2,009,529 HFrEF patients, 57.8% were male, and mean age was 73.8 ± 12.1 years. Among 9,257,514 HFpEF patients, 42.7% were male, and mean age was 73.0 ± 12.1 years. The proportion of spironolactone utilization following HFrEF diagnosis was 20.7% versus 7.6% after HFpEF. The median time (days) to initiation of spironolactone after HFrEF diagnosis was 90 (IQR: 19–385) versus 286 (IQR: 57–851) after HFpEF diagnosis. The median duration (days) of first treatment episode in HFrEF patients was 120 (IQR: 44–321) and 114 (IQR: 32–301) for HFpEF patients. The median dose was similar (25 mg/day) for both HF cohorts. Conclusion: Findings of low real-world utilization of spironolactone from our large, geographically, and demographically diverse multi-site study in the US are consistent with reports from smaller studies in the literature. Similar spironolactone dosing and duration were observed in both the HFpEF and HFrEF cohorts. Future research characterizing spironolactone treated and untreated HFpEF cohorts will be needed to identify treatment gaps.

Power Of Breathing In Heart Failure With Preserved Ejection Fraction During Exercise

Heart failure patients with preserved ejection fraction (HFpEF) exhibit impaired exercise tolerance, while the underlying mechanisms are unclear. HFpEF patients exhibit alterations to the pulmonary system at rest; however, it is unknown if these alterations translate to a higher power of breathing (POB) during exercise, which may contribute to exercise intolerance. PURPOSE: To compare the total POB and its components (inspiratory elastic and resistive and expiratory resistive POB) in HFpEF and healthy controls at matched ventilations (VE). We hypothesized that HFpEF compared to healthy controls (CTL) would exhibit greater total POB as a result of greater inspiratory elastic and resistive POB and expiratory resistive POB. METHODS: HFpEF (n = 10; age: 73 ± 7 yrs; BMI: 32 ± 4 kg/m2; EF: 62 ± 4%) and CTL (n = 10; age: 71 ± 8 yrs; BMI: 28 ± 3 kg/m2) were recruited for this study. All performed an incremental cycling test to volitional fatigue. Esophageal pressure and ventilatory variables were measured at matched VE (i.e. 30 and 50 L/min) during exercise. Inspiratory elastic and resistive as well as expiratory resistive POB were quantified using the Otis method. RESULTS: At VE of 30 and 50 L/min, HFpEF exhibited smaller tidal volumes and greater breathing frequencies compared to CTL (all, p < 0.05). HFpEF compared to CTL had greater total POB at VE of 30 (37 ± 13 vs. 20 ± 9 J/min) and 50 L/min (71 ± 13 vs. 45 ± 13 J/min, p < 0.05 for both). At VE of 30 and 50 L/min, HFpEF compared to CTL had greater inspiratory resistive POB (30 L/min: 13 ± 5 vs. 7 ± 4 J/min; 50 L/min: 27 ± 4 vs.15 ± 4 J/min) and expiratory resistive POB (30 L/min:15 ± 10 vs. 2 ± 2 J/min; 50 L/min: 26 ± 11 vs. 8 ± 12 J/min, all, p < 0.05). Inspiratory elastic POB was not different between groups at VE of 30 and 50 L/min (both, p > 0.05). CONCLUSIONS: These data demonstrate that the HFpEF syndrome is associated with pulmonary alterations eliciting a greater POB during exercise due to greater inspiratory and expiratory resistive POB. These findings suggest that the respiratory muscles may necessitate an increased blood flow demand in HFpEF compared to healthy controls for a given VE during exercise.

Abstract 10528: Exaggerated Inspiratory Muscle Metaboreflex in Heart Failure with Preserved Ejection Fraction

Introduction: Heart failure patients with preserved ejection fraction (HFpEF) may exhibit inspiratory muscle dysfunction potentially contributing to exercise intolerance. Activation of neural afferents in response to inspiratory muscle contraction (metaboreflex) elicits increases in mean arterial pressure (MAP) and leg vascular resistance (LVR) through enhanced sympathetic outflow leading to decreases in leg blood flow (LBF) in healthy humans. It is unknown if HFpEF patients exhibit exaggerated cardiovascular responses to inspiratory muscle metaboreflex activation. Hypothesis: We hypothesize that patients with HFpEF will exhibit a greater increase in MAP and LVR with a decrease in LBF during inspiratory muscle metaboreflex activation than controls. Methods: HFpEF patients (n=15, 10M/5W, 69±10 yrs; 33±4 kg/m2) and controls (n=14; 10M/4W; 70±8 yrs; 28±4 kg/m2) performed inspiratory resistive breathing tasks (IRBT) at 2% and 60% of their maximal inspiratory pressure. During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured by photoplethysmography, venous norepinephrine was measured, LBF was measured by near-infrared spectroscopy and indocyanine green dye injections, and LVR was calculated. Results: During the 2% IRBT, there were no differences between groups in the changes from rest in MAP (HFpEF: 2±4 vs. CTL: 3±4 mmHg) or LBF (HFpEF: 1±14 vs. CTL: 1±12%) (both, p&gt;0.05). During the 60% IRBT, venous norepinephrine increased from rest in HFpEF and controls (p&lt;0.05), while no differences existed between groups (p&gt;0.05). During the 60% IRBT, HFpEF patients, compared to controls, exhibited a greater increase from rest in MAP (HFpEF: 16±7 vs. CTL: 10±6 mmHg) and LVR (HFpEF: 76±45 vs. CTL: 32±19%) coupled with a greater decrease in LBF (HFpEF: -32±14 vs. CTL: -17±9%) (all, p&lt;0.05). Conclusions: These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared to healthy individuals. These findings have important implications for the integrative physiology of exercise in HFpEF patients.

Impact of iron deficiency on prognosis of heart failure patients with preserved ejection fraction

Objective: To investigate the impact of iron deficiency (ID) on prognosis in heart failure patients with preserved ejection fraction (HFpEF). Methods: A total of 215 consecutive patients with HFpEF, who visited the cardiovascular outpatient department of Beijing Anzhen Hospital, were enrolled in this prospective study. The plasma ferritin level and transferin saturation were measured. Patients were divided into two groups: ID group and non-ID group. ID patients were further divided into absolute ID subgroup and functional ID subgroup. Patients were followed up to 1 year. The endpoints of the study were all-cause mortality and rehospitalization for heart failure (HF). The independent predictors of outcome were determined by Cox regression model. The quality of life of patients was evaluated at the end of the follow-up. Results: The age of this patient cohort was (67±8) years, 39.1% patients were male. The prevalence of ID was 54.4%. Within one year of follow-up, 37 patients (17.2%) died and 70 patients (32.6%) were rehospitalized for HF. Compared to non-ID group, patients in ID group were older, had higher heart rate, lower plasma hemoglobin level and estimated glomerular filtration rate (eGFR) value, had a higher prevalence of anemia and chronic kidney disease (P all<0.05). Kaplan-Meier curves showed that all-cause mortality and rehospitalization for HF in HFpEF patients with ID were higher than patients without ID, and prognosis was similar between patients with absolute ID and functional ID. Multivariable regression analysis showed that ID was an independent predictor for all-cause mortality and rehospitalization for HF in HFpEF patients. The of 6 minutes walking distance was shorter ((356.0±98.3)m vs. (389.2±94.3)m, P=0.023), and the value in Kansas city cardiomyopathy questionnaire was lower ((58.06±10.43) m vs. (61.51±11.64) m, P = 0.039) in patients with ID than patients without ID. Conclusion: In patients with chronic HFpEF, ID is an independent predictor for all-cause mortality and rehospitalization for HF at one year of follow-up, independent of the types of ID.

Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy.

AimsAs evidenced by scintigraphy imaging, the prevalence of transthyretin (TTR) cardiac amyloidosis in heart failure patients with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH) ranges between 13% and 19%. The natural evolution of cardiac amyloidosis begins with the deposition of amyloid material in the myocardium, with LVH ensuing at later stages. With current imaging modalities, it is possible to detect TTR cardiac amyloidosis before the hypertrophic stage. The aim of this study was to determine the prevalence of TTR cardiac amyloidosis in HFpEF patients without LVH.Methods and resultsThe study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99‐Tc‐DPD scintigraphy in the absence of monoclonal protein expansion in blood. Transthyretin gene sequencing was performed in positive patients. From July 2017 to January 2020, 329 patients with HFpEF and LV thickness <12 mm were identified. After exclusions, 58 patients completed the study with cardiac scintigraphy (79 years, 54% men; median LVEF 60% and LV wall thickness 10.5 mm). Three patients (5.2%) were positive for TTR cardiac amyloidosis; genetic analysis excluded the presence of hereditary TTR amyloidosis. Positive patients baseline characteristics (84 years, 67% men, LVEF 60%, and LV wall thickness 11 mm) were similar to patients without TTR, except for troponin levels (0.05 vs. 0.02 ng/mL, P = 0.03) and glomerular filtration rate (82 vs. 60 mL/min, P = 0.032), which were higher in TTR patients.ConclusionsIn a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Early diagnosis of cardiac involvement in TTR amyloidosis (before manifest LVH) would seem recommendable because newly approved specific treatments can prevent additional deposition of amyloid material.

Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing.

Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3-6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88-0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs). A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.

Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial)

Despite improvements in the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), established therapy for heart failure patients with preserved ejection fraction (HFpEF) is lacking. Additionally, ischemic heart disease adversely impacts the clinical course of HFrEF patients; however, its role in HFpEF is not fully understood. We conducted a post hoc analysis of propensity score matched patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial to compare HFpEF patients with versus without myocardial ischemia in terms of major adverse renal and/or cardiac events (MARCE). Of 3,445 participants, the prevalence of ischemia was 59%. For this analysis, we included 1,747 ischemic patients and 1,207 propensity matched nonischemic patients. Ischemia was associated with a 20% increased risk (HR = 1.20, 95% confidence interval [CI] = 1.042 to 1.382, p value = 0.0112) of major adverse renal and/or cardiac events (MARCE) in adjusted analyses. Other important predictors of MARCE were diabetes (hazard ratio [HR] = 1.60, 95% CI = 1.38 to 1.87, p <0.0001), dyslipidemia (HR = 1.30, 95% CI = 1.10 to 1.52, p = 0.001) and smoking (HR = 1.33, 95% CI = 1.04 to 1.69, p = 0.0197). Revascularization was not significantly associated with MARCE in the subgroup of ischemic HFpEF patients. Future work is warranted to develop tailored interventions for patients with both HFpEF and ischemic heart disease to mitigate the risk of MARCE .

Evaluating diastolic and systolic reserve by strain imaging during resistance exercise training in heart failure with preserved ejection fraction

Abstract Background Exercise intolerance is the cardinal manifestation of heart failure (HF), yet its underlying mechanism(s) remain poorly understood. Measures of ventricular function such as ejection fraction often have no relationship with exercise capacity in HF. 2D-STE has proved to be more reliable method to evaluate myocardial mechanical function. Our hypothesis is Resistance exercise training (Resist-HFpEF) will improve exercise tolerance and exertional symptoms in patients with HFpEF. Purpose The study aims to evaluate myocardial mechanical function by strain imaging during resistance exercise training in Heart Failure patients with Preserved Ejection Fraction (HFpEF) Methods This is a single centre prospective pilot study. 24 HFpEF patients were enrolled and their baseline comorbidities were recorded. Baseline 2D-STE imaging was performed at rest and during exercise (Visit 1). Patients were then randomized to either a novel resistance exercise training program for 36 sessions (3 sessions per week for 12 weeks) or a standard of care control group. 2D STE imaging was then repeated at follow-up (Visit 2). Peak Global Longitudinal strain (GLS), systolic strain rate (SSR), early diastolic strain rate (SRe) were measured offline. Results Mean age of the Rehab cohort was 68.57±10.52 years and the control cohort was 68.1±6.47 years. 23 study subjects were male (96%). 17% of the study subjects were hypertensive, 63% were diabetic, 42% had NYHA I, 46% had NYHA II and 13% had NYHA III of heart failure. The mean LV ejection fraction in the control and Rehab group after the training program at rest was 61.88±2.26% &amp; 54.74±2.07% (p-value 0.04) and during exercise was 59.90±2.05% and 53.13±2.05% (p-value 0.04). The peak GLS was −18.80±4.29% and −17.7±2.21% in controls during rest and exercise at Visit 1 (p-value 0.27) while the rehab cohort had −18.71±4.7% and −20.82±2.4% respectively (p-value 0.0268). The peak GLS was −17.40±3.05% and −17.96±2.65% in controls during rest and exercise at Visit 2 (p-value 0.3430) while rehab cohort had −17.97±6.21% and −16.57±3.82% respectively (p-value 0.67). (Figure 1a and 1b shows GLS, SRS, SRe at Baseline and after exercise program respectively) Conclusion This pilot study suggest systolic and diastolic reserve can be measured reliably during low grade exercise. These results could reflect improvement in clinical status and exercise tolerance. Figure 1. Comparison of peak GLS, SSR, SRe amongst HFpEF patients at rest and during exercise before and after the rehab training program. Funding Acknowledgement Type of funding source: None

Association of physical activity and risk of atrial fibrillation in heart failure with preserved ejection fraction

Background and aimsPhysical activity (PA) could modify the risk of atrial fibrillation (AF) in the general population and mortality in heart failure patients with preserved ejection fraction (HFpEF). HFpEF patients are frequently concomitant with AF, but whether PA could modify the risk of AF in HFpEF patients remains undiscovered. Method and resultsWe performed a post hoc analysis of the TOPCAT trial. Patients without AF at baseline and with data on PA (n = 652) were included. The association between PA and risk of AF occurrence was explored using the Cox proportional hazard model. During a median follow-up of 2.84 years, 9.4% of the studied patients (n = 60) had an occurrence of AF. When PA was analyzed as a continuous variable, every ten-fold increase of PA was associated with a 42.8% risk reduction of AF occurrence (hazard ratio [HR] 0.572, 95% CI 0.357–0.916, p = 0.020). When HFpEF patients were divided into three tertile groups according to PA levels, patients in the second tertile (HR 0.507, 95% CI 0.272–0.946, p = 0.033) and the third tertile (HR 0.487, 95% CI 0.261–0.908, p = 0.024) had significantly lower risks of AF occurrence when compared to those in the first tertile. ConclusionsOur current results suggest that a higher PA level associates with a lower risk of AF in HFpEF patients. Clinical trial registrationURL: https://clinicaltrials.gov. Unique identifier: NCT00094302.

Does Chronic Kidney Disease Facilitate Malignant Myocardial Fibrosis in Heart Failure with Preserved Ejection Fraction of Hypertensive Origin?

In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes. As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination. A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019). The E:e’ ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e’ ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients.

The clinical characteristics of acute heart failure patients with mid-range ejection fraction in Turkey: A subgroup analysis from journey HF-TR study

Background: Heart failure (HF) is a clinical syndrome characterized with a wide spectrum of left ventricular (LV) structural and functional abnormalities. LV ejection fraction (EF) is considered important with respect to classifying HF patients because of differing patient demographics and prognosis; as well as the response to HF therapies. We aimed to investigate the clinical characteristics, demographics, in-hospital management and in-hospital outcome of HF patients with mid-range EF (HFmrEF) in comparison with those with HF patients with reduced EF (HFrEF) or HF patients with preserved EF (HFpEF) in a large acute HF (AHF) cohort. Materials-Methods and Results: The Journey HF-TR study is a multicenter, and observational registry. One thousand six hundred and six patients who were diagnosed with AHF were enrolled in this study. The mean age was 67.8 ± 13.0 years and 57.2% of the study population was male. Patients were classified as HFrEF (n = 1028, 64%), HFmrEF (n = 305, 19%), and HFpEF (n = 273, 17%) according to LVEF. HFmrEF patients were elder than HFrEF patients but younger than HFpEF patients and the female proportion was the highest in HFpEF group followed by HFmrEF and HFrEF groups (P < 0.001 and P = 0.03, respectively). The prevalence of coronary artery disease was 56.7% in HFmrEF patients. It was lower than HFrEF patients (65.2%) and higher than HFpEF patients (41.4%) (P < 0.001). The prescription of evidence-based HF drugs (Renin-Angiotensin-System blocker, beta-blocker, mineralocorticoid receptor antagonist) was similar in HFrEF and HFmrEF patients and higher than HFpEF patients. The in-hospital mortality rate was the lowest in patients with HFmrEF (1.8%, 7.3%, and 7.5%, respectively for HFmrEF, HFrEF, and HFpEF patients) (P < 0.001). Conclusion: Patients with HFmrEF has unique clinical, echocardiographic, hemodynamic, and biomarker features compared with HFrEF and HFpEF. However, patients with HFmrEF seem to be more similar to HFrEF, in terms of etiology and use of guideline recommended medical therapy.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

Backgroundβ-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF.MethodsFrom the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations.ResultsBB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34–0.82).ConclusionIn the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

A new algorithm for optimization of rate-adaptive pacing improves exercise tolerance in patients with HFpEF.

To develop an algorithm for optimization of rate-adaptive pacing settings in heart failure patients with preserved ejection fraction (HFpEF) and permanent cardiac pacing. This is a prospective randomized controlled study. A total of 54 patients with HFpEF, permanent atrial fibrillation (AF), and VVIR pacing were randomized to an intervention group with optimization of rate-adaptation parameters by using cardiopulmonary exercise testing (CPET) and pacemaker stress echocardiography (PASE), and to a control group with conventional programming. CPET, 6-min walk test (6-mwt), echocardiography (echo), Duke Activity Status Index (DASI), and Minnesota questionnaire (MLHFQ) were performed at baseline and after 3 months. PASE was used to exclude exercise-induced ischemia and to determine safe upper sensor rate. Pacing parameters were corrected to achieve optimal heart rate increments of 3-6bpm for 1mL/min/kg of VO2 (oxygen uptake). After 3 months, the intervention group demonstrated significant improvement of VO2 peak by 1.64±1.6mL/min/kg, anaerobic threshold by 1.33±1.3mL/min/kg, exercise time by 170±98s, 6-mwt distance by 75±63m (P<.0001 for all), DASI by 5.23 points (P=.009), MLHFQ-score (reduction by 9 points, P<.0001), and echo parameters (decrease in LA volume from 108 (84; 132) to 95 (85; 130) mL, P=.026; E/e' from 11.7±3.2 to 10.4±2.9, P=.025; systolic pulmonary artery pressure (SPAP) from 44±14 to 39±12mm Hg, P= .001) compared to the control group. An algorithm incorporating CPET and PASE for optimal programming of rate-adaptation parameters is a valuable tool to improve exercise capacity in HFpEF patients with permanent AF and VVIR pacing who remain exercise intolerant after conventional programming.

Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction

Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients.