scholarly journals Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure with Reduced Ejection Fraction

Author(s):  
Sean P. Murphy ◽  
Margaret F. Prescott ◽  
Alan S. Maisel ◽  
Javed Butler ◽  
Ileana L. Piña ◽  
...  

Background : Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and soluble suppressor of tumorigenicity-2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF) treated with S/V is uncertain. Methods : In a prospective study of S/V in patients with HFrEF, this pre-specified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate Latent Growth Curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction (LVEF) and left atrial volume index (LAVi). Results : 715 out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline LVEF and LAVi were 29% and 40 ml/m 2 , respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/ml, hs-cTnT of 15.9 ng/L and sST2 of 24.7 ng/ml. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI: -35.1% to -20.7%; p<.001) for NT-proBNP; -6.7% (95% CI: -8.8% to -4.7%; p<.001) for hs-cTnT; and -1.6% (95% CI: -2.9% to -0.4%; p<.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in LVEF and LAVi. There was no association between changes in sST2 and changes in other measures. Conclusions : Following initiation of S/V, NT-proBNP, hs-cTnT and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with LA and LV reverse remodeling. Registration : URL: ClinicalTrials.gov; Unique Identifier: NCT02887183

2012 ◽  
Vol 9 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Otto A Smiseth ◽  
Anders Opdahl ◽  
Espen Boe ◽  
Helge Skulstad

Heart failure with preserved left ventricular ejection fraction (HF-PEF), sometimes named diastolic heart failure, is a common condition most frequently seen in the elderly and is associated with arterial hypertension and left ventricular (LV) hypertrophy. Symptoms are attributed to a stiff left ventricle with compensatory elevation of filling pressure and reduced ability to increase stroke volume by the Frank-Starling mechanism. LV interaction with stiff arteries aggravates these problems. Prognosis is almost as severe as for heart failure with reduced ejection fraction (HF-REF), in part reflecting co-morbidities. Before the diagnosis of HF-PEF is made, non-cardiac etiologies must be excluded. Due to the non-specific nature of heart failure symptoms, it is essential to search for objective evidence of diastolic dysfunction which, in the absence of invasive data, is done by echocardiography and demonstration of signs of elevated LV filling pressure, impaired LV relaxation, or increased LV diastolic stiffness. Antihypertensive treatment can effectively prevent HF-PEF. Treatment of HF-PEF is symptomatic, with similar drugs as in HF-REF.


Angiology ◽  
2021 ◽  
pp. 000331972110473
Author(s):  
Umut Karabulut ◽  
Kudret Keskin ◽  
Dilay Karabulut ◽  
Ece Yiğit ◽  
Zerrin Yiğit

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.


2021 ◽  
Vol 26 (1) ◽  
pp. 4200
Author(s):  
I. V. Zhirov ◽  
N. V. Safronova ◽  
Yu. F. Osmolovskaya ◽  
S. N. Тereschenko

Heart failure (HF) and atrial fibrillation (AF) are the most common cardiovascular conditions in clinical practice and frequently coexist. The number of patients with HF and AF is increasing every year.Aim. To analyze the effect of clinical course and management of HF and AF on the outcomes.Material and methods. The data of 1,003 patients from the first Russian register of patients with HF and AF (RIF-CHF) were analyzed. The endpoints included hospitalization due to decompensated HF, cardiovascular mortality, thromboembolic events, and major bleeding. Predictors of unfavorable outcomes were analyzed separately for patients with HF with preserved ejection fraction (AF+HFpEF), mid-range ejection fraction (AF+HFmrEF), and reduced ejection fraction (AF+HFrEF).Results. Among all patients with HF, 39% had HFpEF, 15% — HFmrEF, and 46% — HFrEF. A total of 57,2% of patients were rehospitalized due to decompensated HF within one year. Hospitalization risk was the highest for HFmrEF patients (66%, p=0,017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15,5% vs 5,4% in other groups, p<0,001) but not ischemic stroke (2,4% vs 3%, p=0,776). Patients with HFpEF had lower risk to achieve the composite endpoint (stroke+MI+cardiovascular death) as compared to patients with HFmrEF and HFrEF (12,7% vs 22% and 25,5%, p<0,001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and selected therapy had different effects on the risk of unfavorable outcomes depending on ejection fraction group.Conclusion. Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with unfavorable outcomes. The demographic and clinical characteristics of patients with mid-range ejection fraction demonstrate that these patients need to be studied as a separate cohort.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
V Artola ◽  
B Santema ◽  
R De With ◽  
B Nguyen ◽  
D Linz ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie. Grant support from the Dutch Heart Foundation [NHS2010B233] Background. Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are two cardiovascular conditions that often coexist. Overlapping symptoms, biomarker profile, and echocardiographic changes hinder the diagnosis of underlying HFpEF in patients with AF and suggest that both conditions might reflect similar remodelling processes in the heart. Purpose. To assess cardiac remodelling in AF patients with versus without concomitant HFpEF by transthoracic echocardiography, focusing on atrial dimension and strain. Methods. We selected 120 patients included in AF-RISK, a prospective, observational, multicentre study aiming to identify a risk profile to guide atrial fibrillation therapy study. Patients had paroxysmal AF diagnosed within three years before inclusion, had a left ventricular ejection fraction (LVEF) ≥50% and were in sinus rhythm at the moment of performing echocardiography and blood sampling. Patients were matched by nearest neighbour by age and sex with a 1:1 ratio and were classified into two groups: 1) AF with HFpEF (n = 60) and 2) AF without HFpEF (n = 60). The diagnosis of HFpEF was based on the 2016 ESC heart failure guidelines, including symptoms and signs of heart failure, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥125pg/ml, and one of the following echocardiographic measures: left atrium volume index (LAVI) &gt;34ml/m2, left ventricular mass index ≥115g/m2 for men and ≥95g/m2 for women, average E/e’ ≥13cm/s and average e’ &lt;9cm/s. Measurements of reservoir, conduit and contraction strain of both atria were performed in apical four-chamber by echocardiography (GE, EchoPac BT12). Associations of clinical and echocardiographic characteristics were tested for collinearity by multivariable logistic regression analyses. LAVI, LV mass index and NT-proBNP were excluded from multivariable analysis since these markers were part of the HFpEF diagnostic criteria. Results. Patients with paroxysmal AF and concomitant HFpEF had more often hypertension (72% vs. 45%, P = 0.005), had more impaired strain phases of both the left and right atria (figure 1), had comparable LVEF and global longitudinal strain (GLS) (P = 0.168 and P = 0.212, respectively). In a model adjusted for the number of comorbidities and sex, LA contraction decrease was associated with presence of HFpEF (odds ratio per 1% LA contraction-percent was 0.94, 95% confidence interval 0.87–0.99, P = 0.042). LA contraction was not explained by LAVI in patients with concomitant HFpEF (Spearman’s rho= -0.07, P = 0.08). Conclusion. Our results show that atrial function may differentiate paroxysmal AF patients with HFpEF from those without HFpEF. In patients with paroxysmal AF, more impaired strain phases of the left and right atria were associated with concomitant HFpEF, whereas ventricular function, reflected by LVEF and GLS, did not differ. Abstract Figure. Strain distribution of both atria


2021 ◽  
Author(s):  
Mohammad Abumayyaleh ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Christina Pilsinger ◽  
Katherine Sattler ◽  
...  

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).


2020 ◽  
Vol 9 (6) ◽  
pp. 1897 ◽  
Author(s):  
Francesco Giallauria ◽  
Giuseppe Vitale ◽  
Mario Pacileo ◽  
Anna Di Lorenzo ◽  
Alessandro Oliviero ◽  
...  

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.


Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001305
Author(s):  
Sashiananthan Ganesananthan ◽  
Nisar Shah ◽  
Parin Shah ◽  
Hossam Elsayed ◽  
Julie Phillips ◽  
...  

BackgroundSacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables.Methods and resultsFrom June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin–angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, p<0.001; diastolic blood pressure 72 vs 68 mm Hg, p=0.004), New York Heart Association functional classification score (2.3 vs 1.9, p<0.001), Minnesota Living with Heart Failure Questionnaire score (46 vs 38, p=0.016), left ventricular ejection fraction (26% vs 33%, p<0.001) and left ventricular end systolic diameter (5.2 vs 4.9 cm, p=0.013) compared with baseline. There were no significant changes in renal function or serum potassium.ConclusionThis study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.


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