Heart Failure And Preserved Ejection Fraction Research Articles

Hospitalization after hydroxychloroquine initiation in patients with heart failure with preserved ejection fraction and autoimmune disease.

Hydroxychloroquine (HCQ) reduces cardiovascular events among patients with autoimmune disorders and is being evaluated as a therapeutic option for populations with high-risk cardiovascular disease. However, recent studies have raised concerns about HCQ use and cardiovascular events. To assess the association of HCQ initiation with heart failure-related and all-cause hospitalizations among patients with heart failure and preserved ejection fraction (HFpEF). We conducted a cohort study of patients aged ≥18 years with diagnosed HFpEF and autoimmune disease using MarketScan Commercial and Medicare Supplemental databases (2007-2019). Patients were required to initiate HCQ after their first HFpEF diagnosis (HCQ users) or not (HCQ nonusers). For the patients in the HCQ users group, the first HCQ prescription date was assigned as the index date. Index date for the HCQ nonuser group was assigned by prescription-time distribution matching HCQ users, by utilizing the number of days from HFpEF diagnosis to the first HCQ prescription. After 1:≥3 propensity score (PS) matching, Cox proportional hazards regression models were used to compare HF-related and all-cause hospitalizations between users and nonusers. After PS matching, 2229 patients (592 HCQ users and 1637 HCQ nonusers) were included. After controlling for covariates, patients who received HCQ had lower risks of HF-related hospitalization (adjusted hazard ratio, 0.44; 95% CI, 0.24-0.82) and all-cause hospitalization (adjusted hazard ratio, 0.69; 95% CI, 0.57-0.83) compared with patients not using HCQ. Among patients with HFpEF and autoimmune disease, initiation of HCQ use was associated with a decreased risk of HF-related and all-cause hospitalizations.

Clinical correlates and prognostic impact of cognitive decline in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF

Abstract Background Cognitive decline is common in patients with heart failure (HF), but its clinical correlates and prognostic impact are not well understood in this population. Purpose To examine the baseline variables associated with cognitive decline and the associations between cognitive decline and HF outcomes in patients with heart failure and preserved ejection fraction (HFpEF). Methods We analyzed cognitive function, as measured by the Mini-Mental State Examination (MMSE), in 2895 patients with HFpEF enrolled in a pre-specified sub-study of PARAGON-HF. Logistic regression analysis was performed to determine the factors associated with cognitive decline i.e., a decrease in MMSE score of ≥3 points by 48 weeks. Time-updated Cox proportional hazards regressions and semiparametric proportional rates models were used to examine the subsequent risk of clinical outcomes after a decline in MMSE scores of ≥1-, 2- and 3-points during follow-up respectively, adjusted for known prognostic variables including NT-proBNP and baseline MMSE. Results A total of 450 (15.5% of the population) patients experienced a decrease in MMSE score of ≥3 points from baseline, at any follow-up visit. The corresponding number for a decrease in MMSE score of ≥2 points and ≥1 point was 755 (26.1%) and 1231 (42.5%), respectively. Independent predictors of cognitive decline at 48 weeks included older age, living in Latin America or the Asia/Pacific region, ischemic etiology, prior HF hospitalization, history of stroke/TIA, and lower serum albumin level (Figure 1). There was a graded relationship between the size of the decrease in MMSE score from baseline and the subsequent risk of mortality. Notably, a decrease of ≥3 points was associated with a 50% increase in the subsequent risk of death from any cause (adjusted HR 1.53, 95% CI 1.10-2.11) and a 90% elevation in risk of death from cardiovascular causes (1.89, 1.25-2.86), respectively, after extensive adjustment for known prognostic variables and baseline MMSE score. By contrast, cognitive decline during follow-up was not associated with a higher risk of HF hospitalization or the composite of HF hospitalization or CV death (Figure 2). Conclusions In patients with HFpEF, a decline in MMSE score during follow-up is independently associated with a graded increase in the risk for mortality, but not of HF hospitalization.The predictors for cognitive declineRisk of outcomes after a decline in MMSE

Diversity of heart failure phenotypes in transthyretin amyloid cardiomyopathy. More than just heart failure with preserved ejection fraction

Introduction Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography. Methods This multicentre, retrospective observational study included patients diagnosed with ATTR-CM between 2015–2023. The diagnosis was based on a positive cardiac biopsy or positive bone scintigraphy without monoclonal gammopathy. Echocardiographic measurements were categorized according to LV ejection fraction (LVEF) into HFpEF (LVEF ≥50%), HF with mildly reduced EF (HFmrEF, LVEF 40–49%), and HF with reduced EF (HFrEF, LVEF <40%). LV cavity size was categorized by LV end-diastolic diameter (LVEDD) and volume index (LVEDVi) as normal, moderately increased and severe dilatation. Results The study included 135 patients with ATTR-CM (mean age, 78 years; 89% male; 89% wild-type ATTR-CM). Most patients were screened for ATTR-CM because of unexplained HF and increased LV wall thickness (57%). Echocardiography showed LVEF <50% in 60% of the patients, with a significant portion presenting with HFrEF. Patients with LVEF <50% had higher NYHA class and elevated N-terminal pro-B-type natriuretic peptide levels than HFpEF patients. LV dilatation was observed in 43% of the patients, with 10% presenting with both LVEF <50% and severe LV dilatation. Conclusion This study revealed significant variability in HF phenotypes among patients with ATTR-CM, from HFpEF without LV dilatation to HFrEF with severe LV dilatation. Relying solely on HFpEF for screening may lead to under-diagnosis. These findings suggest the need for more comprehensive diagnostic criteria beyond echocardiographic measures to improve ATTR-CM detection and management.

Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction

Human cardiomyocytes from very obese patients with heart failure and preserved ejection fraction (HFpEF) have markedly depressed calcium-activated tension and increased resting stiffness. To test if either are recapitulated by obese-HFpEF animal models, tension‑calcium and tension-sarcomere length relations were measured in myocytes from mice on a high fat diet (HFD) with L-NAME, ZSF1 rats, and Göttingen minipigs on HFD + DOCA (MP). Only MP myocytes displayed reduced Ca2+-activated tension, and none exhibited increased resting stiffness versus respective controls. Consistent with prior myofibrillar data, crossbridge attachment and detachment rates at matched tension were slower in rodent models, and detachment slower in MP.

Assessing Static Balance, Balance Confidence, and Fall Rate in Patients with Heart Failure and Preserved Ejection Fraction: A Comprehensive Analysis.

Chronic heart failure (CHF) is a complex clinical syndrome, associated with frailty, higher fall rates, and frequent hospitalizations. Heart Failure (HF) and preserved ejection fraction (HFpEF) is defined as a condition where a patient with HF have a diagnosis of left ventricular ejection fraction (LVEF) of ≥ 50%. The risk of HFpEF increases with age and is related to higher non-cardiovascular mortality. The aim of this study was to evaluate static balance and examine the effect of task difficulty on the discriminating power of balance control between patients with HFpEF (Patients with HFpEF) and their healthy controls. Moreover, the associations between static balance parameters, balance confidence, falls, lean muscle mass, and strength were assessed. Seventy two patients with HFpEF (mean age: 66.0 ± 11.6 years) and seventy two age- and gender-matched healthy individuals (mean age: 65.3 ± 9.5 years) participated in this study. Participants underwent a 30 s bilateral stance (BS) test and a 20 s Tandem-Romberg stance (TRS) on a force platform, evaluating the Range and Standard Deviation of Center of Pressure (COP) displacement parameters in both axes. Balance confidence was evaluated by the Activities-Specific Balance Confidence (ABC) Scale, and the number of falls during the last year was recorded. Lower limb strength was measured using an isokinetic dynamometer, isometric leg strength, and a Sit-to-Stand test. Bioelectrical impedance analysis was conducted to assess lean fat mass, lean fat mass index, and lean%. Patients with HFpEF presented with lower static balance in BS and TRS compared to healthy controls (p < 0.05), lower balance confidence by 21.5% (p < 0.05), and a higher incidence of falls by 72.9% (p < 0.05). BS was a better descriptor of the between-group difference. Furthermore, static balance, assessed in controlled lab conditions, was found to have little if no relationship to falls, strength, lean muscle mass, and balance confidence. Although no correlation was noted between the static balance parameters and falls, the fall rate was related to balance confidence, age, muscle strength, and lean fat.

Endovascular Ablation of the Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction

Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF). To explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM). This was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024. SAVM vs sham control procedure. The primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP. A total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, -0.03 mm Hg; 95% CI, -2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, -6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, -9.2% to 18.8%; P = .48). Results show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF. ClinicalTrials.gov Identifier: NCT04592445.

Varying effect of atrial fibrillation ablation in patients with heart failure with preserved ejection fraction according to CHA2DS2-VASc score

BackgroundThe impact of comorbidity burden on outcomes of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in patients with heart failure and preserved ejection fraction (HFpEF) remains unclear. ObjectiveThe purpose of this study was to evaluate how comorbidity burden influences the association between RFCA and cardiovascular outcomes in AF patients with HFpEF. MethodsAF patients with HFpEF from the prospective China-AF cohort, recruited between August 2011 and December 2020, were categorized into 2 groups based CHA2DS2-VASc score: low comorbidity burden (score ≤4) and high comorbidity burden (score >4). The associations between RFCA and cardiovascular outcomes and interaction effects of comorbidity burden on these associations were assessed. ResultsAmong 1700 patients with median follow-up of 65.9 months, those in the low comorbidity burden group who received RFCA had a lower risk of composite events (cardiovascular death and ischemic stroke/transient ischemic attack [TIA]) (adjusted hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.21–0.59] and all-cause death (adjusted HR 0.31, 95% CI 0.17–0.54) compared to those without RFCA. However, significant associations were not observed in the high comorbidity burden group. The differences between low and high comorbidity burden groups were significant, with interaction effects noted between comorbidity burden and RFCA for cardiovascular death (Pinteraction = 0.045) and ischemic stroke/TIA (Pinteraction = 0.010). RFCA was associated with a reduced risk of AF recurrence in both comorbidity burden groups. ConclusionRFCA for AF is associated with reduced AF recurrence and improved cardiovascular outcomes in patients with HFpEF. However, these benefits may be limited for patients with a CHA2DS2-VASc score >4 (high comorbidity burden).

Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis

Mineralocorticoid receptor antagonists (MRAs) reduce hospitalisations and death in patients with heart failure and reduced ejection fraction (HFrEF), but the benefit in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF) is unclear. We evaluated the effect of MRAs in four trials that enrolled patients with heart failure across the range of ejection fraction. This is a prespecified, individual patient level meta-analysis of the RALES (spironolactone) and EMPHASIS-HF (eplerenone) trials, which enrolled patients with HFrEF, and of the TOPCAT (spironolactone) and FINEARTS-HF (finerenone) trials, which enrolled patients with HFmrEF or HFpEF. The primary outcome of this meta-analysis was a composite of time to first hospitalisation for heart failure or cardiovascular death. We also estimated the effect of MRAs on components of this composite, total (first or repeat) heart failure hospitalisations (with and without cardiovascular deaths), and all-cause death. Safety outcomes were also assessed, including serum creatinine, estimated glomerular filtration rate, serum potassium, and systolic blood pressure. An interaction between trials and treatment was tested to examine the heterogeneity of effect in these populations. This study is registered with PROSPERO, CRD42024541487. 13 846 patients were included in the four trials. MRAs reduced the risk of cardiovascular death or heart failure hospitalisation (hazard ratio 0·77 [95% CI 0·72-0·83]). There was a statistically significant interaction by trials and treatment (p for interaction=0·0012) due to the greater efficacy in HFrEF (0·66 [0·59-0·73]) compared with HFmrEF or HFpEF (0·87 [0·79-0·95]). We observed significant reductions in heart failure hospitalisation in the HFrEF trials (0·63 [0·55-0·72]) and the HFmrEF or HFpEF trials (0·82 [0·74-0·91]). The same pattern was observed for total heart failure hospitalisations with or without cardiovascular death. Cardiovascular death was reduced in the HFrEF trials (0·72 [0·63-0·82]) but not in the HFmrEF or HFpEF trials (0·92 [0·80-1·05]). All-cause death was also reduced in the HFrEF trials (0·73 [0·65-0·83]) but not in the HFmrEF or HFpEF trials (0·94 [0·85-1·03]). With an MRA, the risk of hyperkalaemia was doubled compared with placebo (odds ratio 2·27 [95% CI 2·02-2·56]), but the incidence of serious hyperkalaemia (serum potassium >6·0 mmol/L) was low (2·9% vs 1·4%); the risk of hypokalaemia (potassium <3·5 mmol/L) was halved (0·51 [0·45-0·57]; 7% vs 14%). Steroidal MRAs reduce the risk of cardiovascular death or heart failure hospitalisation in patients with HFrEF and non-steroidal MRAs reduce this risk in patients with HFmrEF or HFpEF. None.

Why Have We Not Been Able to Demonstrate Reduced Mortality in Patients With HFmrEF/HFpEF?

No randomized controlled trial has yet demonstrated a statistically significant reduction in mortality in patients with heart failure and mildly reduced ejection (HFmrEF) or heart failure and preserved ejection fraction (HFpEF), in contrast to the benefits observed in heart failure with reduced ejection fraction (HFrEF). However, this probably reflects the statistical power of trials to date to show an effect on mortality rather than mechanistic differences between HFmEF/HFpEF and HFrEF or differences in treatment efficacy. Compared to patients with HFrEF, those with HFmrEF/HFpEF have lower mortality rates and a smaller proportion of potentially modifiable cardiovascular deaths (as opposed to unmodifiable noncardiovascular deaths). In addition, some causes of cardiovascular deaths may not be reduced by treatments for HF. Therefore, the low rate of potentially modifiable deaths in patients with HFmrEF/HFpEF, compared with HFrEF, has made it challenging to demonstrate a reduction in death (or cardiovascular death) in trials to date.

Effect of Sodium-Glucose Co-Transporter-2 Inhibitor on Estimated Plasma Volume in a Patient With Heart Failure With Reduced Ejection Fraction and a Patient With Heart Failure With Preserved Ejection Fraction.

The increased diuresis after sodium-glucose cotransporter 2 inhibitor (SGLT2i) was associated with a reduction of the estimated plasma volume (ePV) in type 2 diabetic patients. We hypothesized that the early effect of SGLT2i on ePV may be monitored by the change of biomarkers of hemoconcentration. We analyzed the early- and long-term effect of SGLT2i empagliflozin on the ePV as assessed by biomarkers of hemoconcentration in a nondiabetic patient with heart failure and reduced ejection fraction (HFrEF) and a nondiabetic patient with heart failure and preserved ejection fraction (HFpEF). The ePV was calculated from hemoglobin and hematocrit levels by Duarte formula and ePV change was calculated by Strauss formula. The ePV change was -22.56% between baseline and 1 month, and -37.60% between baseline and 12 months follow-up in a patient with HFrEF, and -6.18% and -16.40% in a patient with HFpEF, respectively. The early effect of SGLT2i on ePV in patients with heart failure may be monitored by biomarkers of hemoconcentration.

Acute clinical outcomes of patients with HFpEF undergoing atrial fibrillation ablation

Abstract Aim Robust data show that atrial fibrillation (AF) ablation can improve left ventricular function and prevent cardiovascular complications in patients with heart failure and reduced ejection fraction. The effectiveness and safety of AF ablation in patients with heart failure and preserved ejection fraction (HFpEF) is less well characterized. Methods We retrospectively analyzed 785 consecutive patients with normal left ventricular function undergoing AF ablation in a high-volume center including 251 with AF and HFpEF. We compared baseline parameters, procedural details and procedural complications by heart failure status. Results Patients with HFpEF (n=251/785) were older (median age 70 years vs. 64 years; p &amp;lt; 0.05) and more frequently female (48.2% vs. 32.2%; p &amp;lt; 0.05) compared to patients without HF. Symptom severity was comparable with a median European Heart Rhythm Association score of 2 in both groups (p &amp;gt; 0.05). Arterial (71.7% vs. 59.7%, p &amp;lt; 0.05), diabetes (16.7% vs. 9.4%, p &amp;lt; 0.05) and dyslipidemia (41.4% vs. 27.2%, p &amp;lt; 0.05) were more common in patients with AF and HFpEF. Acute pulmonary vein isolation (PVI) was achieved in all patients using cryoballoon or radiofrequency energy with similar frequency in both groups (cryoballoon ablation: 37.8% vs. 41.6%; p &amp;gt; 0.05). A subgroup of patients in both groups additionally underwent cavotricuspid isthmus ablation for coexistent atrial flutter (26% vs. 20.7%; p &amp;gt; 0.05). Procedure times (119.4 ± 47.7 min vs. 120.2 ± 48.3 min; p &amp;gt; 0.05) and fluoroscopy times (15.8 ± 10.4 min vs. 15.5 ± 7.1 min; p &amp;gt; 0.05) were comparable. Overall complication rates did not differ (12.7% vs. 10.3%; p &amp;gt; 0.05). While the incidence of pericardial tamponades was slightly higher (2% vs. 0%), other severe and minor complications showed no significant differences, including stroke/transient ischemic attack (TIA; 0.4% vs. 0.6%), major life-threatening bleeding (0% vs. 0.2%), vascular complications (1.6% vs. 2.1%), phrenic nerve palsy (0.8% vs. 1.5%), and pulmonary vein stenosis (0.4 vs. 0%). The mean in-hospital stay for the procedure was 2 days in both groups (p &amp;gt; 0.05). In-hospital recurrence rates were similar (12.4% vs. 17%; p &amp;gt; 0.05), as was the need for electrical cardioversion before discharge (5.6% vs. 6.6%; p &amp;gt; 0.05). Conclusion Patients with HFpEF undergoing AF ablation were older, more frequently female, and have more comorbidities than patients without heart failure. Acute procedural success and acute complication rates appear low. These data encourage randomized evaluations of the safety and efficacy of ablation-based rhythm control therapy in patients with AF and HFpEF.

Urocortin 2 Gene Transfer in Mice Improves Diastolic Function in Heart Failure with Preserved Ejection Fraction

Patients with heart failure and preserved ejection fraction (HFpEF) comprise about 50% of patients with heart failure in the US (&gt;3 million people). There are currently no treatments for HFpEF that prolong life, and few that reduce HF hospitalization rates. The Schlager BPH (Blood Pressure-High) mouse is a genetic model of hypertension, a major contributing factor in left ventricular (LV) diastolic dysfunction and HFpEF. This study test the hypothesis that intravenous (i.v.) delivery of a long-term expression vector encoding murine urocortin 2 (AAV8.m Ucn2) can improve LV diastolic function in mice with impaired LV diastolic function. Twelve male and 12 female BPH mice (21.3±0.5 g; 3.1±0.1 months-old) with an ejection fraction (EF) of 60±2% (echocardiography) were studied. Prior to Ucn2 gene transfer their unsedated systolic/diastolic blood pressures (tail cuff) were (183/146±2/7 mmHg, n=24), conforming the presence of severe hypertension. The BPH mice were separated into two groups (6M &amp; 6F in each group). One group (BPH + Ucn2) received AAV8.m Ucn2 (2x1013 gc/kg, i.v) and the other group (BPH) received saline, i.v. Seven weeks after randomization, LV EF showed a group difference (BPH: 54±2%, n=12; BPH+Ucn2: 74±2%, n=12; p&lt;.0001) that was same as with systolic/diastolic blood pressure (BPH: 183/154±4/4 mmHg, n=12; BPH +Ucn2: 142/117±4/4 mmHg; p&lt;0.0001). In addition, physiological studies conducted in vivo showed accelerated cardiac relaxation in the Ucn2-treated mice (see Tau in Table), indicating superior LV relaxation after Ucn2 gene transfer. Conclusion: Ucn2 gene transfer improves LV diastolic and systolic function in mice with HFpEF, indicating that such a strategy may be applicable in clinical settings. [Formula: see text] Merit grant from the Department of Veterans Affairs (I01 BX003774). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of sacubitril/valsartan according to polypharmacy status in PARAGON-HF.

Patients with heart failure (HF) and preserved ejection fraction (HFpEF) have a particularly high prevalence of comorbidities, often necessitating treatment with many medications. The aim of this study was to evaluate the association between polypharmacy status and outcomes in PARAGON-HF. In this post hoc analysis, baseline medication status was available in 4793 of 4796 patients included in the primary analysis of PARAGON-HF. The effects of sacubitril/valsartan, compared with valsartan, were assessed according to the number of medications at baseline: 683 non-polypharmacy (<5 medications); 2750 polypharmacy (5-9 medications), and 1360 hyper-polypharmacy (≥10 medications). The primary outcome was total HF hospitalizations and cardiovascular deaths. Patients with hyper-polypharmacy were older, had more severe limitations due to HF (worse New York Heart Association class and Kansas City Cardiomyopathy Questionnaire scores), and had greater comorbidity. The non-adjusted risk of the primary outcome was significantly higher in patients taking more medications, and similar trends were seen for HF hospitalization and cardiovascular and all-cause death. The effect of sacubitril/valsartan versus valsartan on the primary outcome from the lowest to highest polypharmacy category was (as a rate ratio): 1.19 (0.76-1.85), 0.94 (0.77-1.15), and 0.77 (0.61-0.96) (pinteraction = 0.16). Treatment-related adverse events were more common in patients in the higher polypharmacy categories but not more common with sacubitril/valsartan, versus valsartan, in any polypharmacy category. Polypharmacy is very common in patients with HFpEF, and those with polypharmacy have worse clinical status and a higher rate of non-fatal and fatal outcomes. The benefit of sacubitril/valsartan was not diminished in patients taking a larger number of medications at baseline.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction-a randomized trial: The NICE study.

There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.

Assessment of the cardiac output at rest and during exercise stress using real-time cardiovascular magnetic resonance imaging in HFpEF-patients

This methodological study aimed to validate the cardiac output (CO) measured by exercise-stress real-time phase-contrast cardiovascular magnetic resonance imaging (CMR) in patients with heart failure and preserved ejection fraction (HFpEF). 68 patients with dyspnea on exertion (NYHA ≥ II) and echocardiographic signs of diastolic dysfunction underwent rest and exercise stress right heart catheterization (RHC) and CMR within 24 h. Patients were diagnosed as overt HFpEF (pulmonary capillary wedge pressure (PCWP) ≥ 15mmHg at rest), masked HFpEF (PCWP ≥ 25mmHg during exercise stress but < 15mmHg at rest) and non-cardiac dyspnea. CO was calculated using RHC as the reference standard, and in CMR by the volumetric stroke volume, conventional phase-contrast and rest and stress real-time phase-contrast imaging. At rest, the CMR based CO showed good agreement with RHC with an ICC of 0.772 for conventional phase-contrast, and 0.872 for real-time phase-contrast measurements. During exercise stress, the agreement of real-time CMR and RHC was good with an ICC of 0.805. Real-time measurements underestimated the CO at rest (Bias:0.71 L/min) and during exercise stress (Bias:1.4 L/min). Patients with overt HFpEF had a significantly lower cardiac index compared to patients with masked HFpEF and with non-cardiac dyspnea during exercise stress, but not at rest. Real-time phase-contrast CO can be assessed with good agreement with the invasive reference standard at rest and during exercise stress. While moderate underestimation of the CO needs to be considered with non-invasive testing, the CO using real-time CMR provides useful clinical information and could help to avoid unnecessary invasive procedures in HFpEF patients.

Ablation for atrial fibrillation improves the outcomes in patients with heart failure with preserved ejection fraction: a single-center cohort study

Abstract Introduction Patients with heart failure and preserved ejection fraction (HFpEF) are frequently associated with atrial fibrillation (AF), and such clinical condition has worse clinical status than those with sinus rhythm. Whether the use of a strategy to maintain sinus rhythm in patients with HFpEF would affect outcomes remains uncertain. Purpose To investigate whether the strategy of AF ablation to maintain sinus rhythm compared to no ablation is associated with improvement of all-cause death and rehospitalization for worsening heart failure in patients with AF and HFpEF. Methods In this retrospective cohort study, a total of 1034 patients with HFpEF and AF (69 [63, 76] years, 478 [46.2%] female) were analyzed, 392 patients who received first-time AF ablation were assigned to the ablation group, and the remaining 642 patients with merely medical therapy were assigned to the no ablation group. The primary end point was a composite of all-cause mortality or rehospitalization for worsening heart failure and was assessed by the Kaplan-Meier method and Cox proportional hazard model. Baseline differences were adjusted by multivariable-adjustment analysis, propensity score-matched analysis, and inverse probability of treatment weighting analysis. Atrial tachycardia/AF recurrence was assessed in a multivariable-adjusted Fine &amp; Gray model, with death treated as a competing risk factor. Results After a median follow-up period of 39 months, the cumulative incidence of the primary end point was significantly lower in the ablation group compared to the no ablation group after multivariable adjustment in the overall cohort (adjusted hazard ratio [HR], 0.65 [95% CI, 0.45-0.94], P = 0.02; incidence rate difference [IRD], -0.39 [95% CI, -0.54 to -0.25]). Analyses for secondary outcomes revealed that clinical benefit produced by AF ablation was mainly driven by rehospitalization for worsening heart failure (adjusted HR, 0.65 [95% CI, 0.44-0.96], P = 0.03) with an estimated IRD of -0.31 (95% CI, -0.45 to -0.18). Results were consistent in the propensity score-matched analysis and inverse probability of treatment weighting analysis. In addition, patients in the ablation group had a 34% relative decrease in the atrial tachycardia/AF recurrence (adjusted HR, 0.66 [95% CI, 0.55-0.81], P &amp;lt; 0.001) relative to no ablation group in the multivariate-adjusted Fine &amp; Gray model. Patients who received AF ablation and maintained sinus rhythm during the follow-up period had a lower risk of the primary end point (P &amp;lt; 0.001 by log-rank test). Conclusion(s) Among HFpEF and AF patients, the strategy of AF ablation to maintain sinus rhythm led to a lower risk of the composite of death from any cause or hospitalization for worsening heart failure.Figure 1.Kaplan–Meier curvesTable 1.Incidence rate and hazard ratio

Right ventricular uncoupling in heart failure with preserved ejection fraction: a simple parameter to predict long-term mortality?

Abstract Introduction Several prognostic models have been developed for risk stratification of mortality in patients with acute heart failure (AHF). eRecent evidence suggests that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcomes in heart failure. Patients with heart failure and preserved ejection fraction (HFpEF) are a heterogeneous population with a wide range of clinical outcomes. However, the prognostic utility of RV-PA uncoupling for predicting long-term mortality in these patients remains elusive. Objective To assess the prognostic value of right ventricle-pulmonary artery coupling for long-term mortality in hospitalized patients with HFpEF. Methods Retrospective analysis of a consecutive, prospective, single-center cohort. Adult patients hospitalized between 2015 and 2020 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) &amp;gt;40% were included. The primary endpoint was long-term all-cause mortality. Ventricular uncoupling was assessed as the ratio of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) estimated from an echocardiogram performed within 3 months of the index hospitalization. Univariable Cox proportional hazards regression models were used to calculate hazard ratios (HR), and multivariable Cox regression was performed with previously analyzed covariates: age, sex, atrial fibrillation, renal dysfunction and E/e'. Results Of 465 patients with HFpEF, 361 (77%) PASP and TAPSE could be estimated simultaneously. During a mean follow-up of 20.9 months, the primary outcome event occurred in 100 patients (27.7%). The optimal cut-off for the primary endpoint was TAPSE/PASP=0.38. Univariable Cox regression showed that RV-PA uncoupling was associated with the primary endpoint of long-term mortality (hazard ratio [HR] 1.96 [95% CI, 1.32-2.92], P=0.001). Kaplan-Meier analysis showed that patients with a ratio &amp;lt;0.38 were at high risk of all-cause mortality (Figure 1). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with long term mortality independent of age, sex, atrial fibrillation, renal dysfunction and E/e' (HR 2.21 [95% CI, 1.26-3.81], P=0.005). Conclusions In patients hospitalized for AHF with preserved ejection fraction, RV-PA uncoupling as determined by the TAPSE/PASP ratio was independently associated with long-term all-cause mortality. TAPSE/PASP was associated with mortality independently of age, sex, renal function, atrial fibrillation and diastolic dysfunction. This simple echocardiographic parameter may identify a population at higher risk for events during follow-up.Kaplan-Meier for all-cause mortality

Abstract 16270: Pulse Pressure Amplification Contributes to the Exaggerated Peripheral Blood Pressure Response to Exercise in Patients With HFpEF

Background: Patients with suspected heart failure and preserved ejection fraction (HFpEF) undergo invasive (right heart catheterization) cardiopulmonary exercise testing (iCPET) to confirm diagnosis. During iCPET peripheral arterial blood pressure (BP) is measured using a brachial cuff or radial arterial catheter. Notably, peripheral BP is typically higher than central BP and this difference is assessed by measuring pulse pressure amplification (PPA; peripheral - central PP; PP = systolic BP [SBP] - diastolic BP). The effect of PPA on the assessment of (exaggerated) exercise BP in HFpEF is unknown. Methods: 20 patients with HFpEF (75% Female; age: 69±7 years, BMI: 38±7 kg/m 2 ) were studied at rest and during submaximal and maximal cycling exercise. We measured radial BP (arterial catheterization) and derived ascending aortic BP using a transfer function applied to radial arterial waveforms (SphygmoCor). Pulse pressure amplification was assessed as radial-aortic pulse pressure. Data were compared with one-way and two-way (Site*Exercise Stage) ANOVA. Results: The increase in radial PP with exercise was greater than aortic PP (Site*Stage P&lt;0.001; Figure A); thus, PPA increased with exercise (ANOVA, P =0.001; Figure B). The increase in PPA was due to a greater increase in radial compared to aortic SBP (Site*Stage P=0.002; Figure C). The change in diastolic pressure was not different between sites (Figure D). Increases in PPA accounted for ~30% of the increase in radial SBP. The incidence of exaggerated exercise SBP (Male: &gt;210 mmHg; Female: &gt;190 mmHg) was higher in the radial artery compared to aorta (95 vs 40 %, χ2&lt;0.001). Conclusion: Peak exercise SBP was ~50 mmHg greater in the radial artery compared to aorta. The marked overestimation of central BP during exercise when measuring peripheral BP leads to misguided interpretation of BP responses to exercise, the magnitude of afterload and has implications for the assessment of ventricular-arterial coupling.

Abstract 13242: Annual Body Weight Change and Subsequent Prognosis in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry

Introduction: Maintaining optimal body weight is important in heart failure management. Weight gain (WG) may signal excessive caloric intake and fluid retention, whereas weight loss (WL) would imply cachexia. Both conditions could affect the prognosis of heart failure with reduced ejection fraction. However, the significance of WG and WL in patients with heart failure and preserved ejection fraction (HFpEF) has not been well established. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. Of 1231 patients who enrolled in the registry, we enrolled 662 patients (age, 82±9 years; females, 54.1%; body mass index, 22.3±4.3kg/m 2 ; atrial fibrillation, 38.3%) whose weight at discharge and one year later were both available. WG and WL were defined as a gain or loss of ≥5% weight between baseline and 1 year, respectively. Other patients who did not demonstrate a significant change in weight were categorized as having a stable weight (SW). All-cause mortality was the primary endpoint. Results: During 1-year, the median body weight slightly increased from 52.1 (interquartile range [IQR]: 45.1-61.9) to 53.0 kg (IQR 45.0-63.0) kg (p &lt;0.001), with a median change of 0.6 kg (IQR: -1.8-2.8). A total of 182 (27%), 125 (19%), and 355 (54%) patients experienced WG, WL, and SW, respectively. During a follow-up of 603 days (IQR: 329-982), 149 patients died. The mortality rate was highest in patients experiencing WL, followed by those experiencing WG and SW (30.2% vs. 21.5% vs. 18.0%, respectively; log-rank p = 0.006). After adjusting for potential confounders, Cox regression analysis revealed that WL, not WG, was independently associated with higher mortality (hazard ratio 2.44 [95% CI 1.51-3.95], p &lt;0.001). Conclusions: Significant number of patients with HFpEF experienced WG and WL within a year. Patients who experienced WL had a higher risk of mortality compared to those who experienced WG and SW. These results highlight the importance of monitoring body weight changes in the management of HFpEF.