Abstract 16477: Sacubitril/valsartan as a Treatment for Resistant Hypertension in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Pardeep S Jhund ◽  
Alice M 1 ◽  
Marc A Pfeffer ◽  
Faiez ZANNAD ◽  
Martin P Lefkowitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Resistant Hypertension ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonist ◽  
Drug Classes ◽  
Neprilysin Inhibitor ◽  
Group 2 ◽  
Design And Methods ◽  
Group 1

Objective: Heart failure with preserved ejection fraction (HFpEF) is typically a hypertensive phenotype and many HFpEF patients have difficult to control hypertension. We examined the effect of neprilysin inhibition on resistant hypertension in HFpEF patients in the PARAGON-HF trial. Patients entered a 1 to 4-week valsartan run-in (target dose 80mg bd), followed by sacubitril/valsartan run-in, before randomization to valsartan or sacubitril/valsartan (target doses 160mg bd or 200mg bd respectively). Design and methods: Patients were examined according to different definitions of resistant hypertension using systolic blood pressure (SBP) at the end of valsartan run-in. Group 1: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a calcium channel blocker (CCB), diuretic and valsartan, Group 2: SBP≥130mmHg despite treatment with a CCB, diuretic and valsartan, or SBP<130mmHg despite treatment with a CCB, diuretic, mineralocorticoid receptor antagonist (MRA) and valsartan, and Group 3: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a CCB, diuretic, MRA and valsartan (≥4 classes of SBP-reducing therapy, including MRA). We examined reduction in SBP from end of valsartan run-in to weeks 4 and 16 after randomization and the proportion of patients with controlled SBP at week 16 on sacubitril/valsartan vs valsartan. Results: Of 4796 patients randomized, criteria for resistant hypertension were fulfilled in 726 (15%) using the Group 1 definition, 1146 (24%) using the Group 2 definition and 132 (3%) in the third group. The combination of neprilysin inhibitor, angiotensin receptor blocker, CCB and diuretic (+/-MRA) reduced SBP and significantly increased the proportion of patients with controlled SBP (Table). Conclusion: Sacubitril/valsartan may be useful in treating resistant hypertension in patients with HFpEF, even in those who continue to have an elevated SBP despite treatment with at least 4 antihypertensive drug classes, including an MRA.

scholarly journals Different Pathophysiology and Outcomes of Heart Failure With Preserved Ejection Fraction Stratified by K-Means Clustering

2020 ◽  
Vol 7 ◽  
Author(s):  
Daisuke Harada ◽  
Hidetsugu Asanoi ◽  
Takahisa Noto ◽  
Junya Takagawa
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Right Ventricle ◽  
Preserved Ejection Fraction ◽  
Stratified Medicine ◽  
Cardiac Events ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Stratified medicine may enable the development of effective treatments for particular groups of patients with heart failure with preserved ejection fraction (HFpEF); however, the heterogeneity of this syndrome makes it difficult to group patients together by common disease features. The aim of the present study was to find new subgroups of HFpEF using machine learning.Methods: K-means clustering was used to stratify patients with HFpEF. We retrospectively enrolled 350 outpatients with HFpEF. Their clinical characteristics, blood sample test results and hemodynamic parameters assessed by echocardiography, electrocardiography and jugular venous pulse, and clinical outcomes were applied to k-means clustering. The optimal k was detected using Hartigan's rule.Results: HFpEF was stratified into four groups. The characteristic feature in group 1 was left ventricular relaxation abnormality. Compared with group 1, patients in groups 2, 3, and 4 had a high mean mitral E/e′ ratio. The estimated glomerular filtration rate was lower in group 2 than in group 3 (median 51 ml/min/1.73 m2 vs. 63 ml/min/1.73 m2p &lt; 0.05). The prevalence of less-distensible right ventricle and atrial fibrillation was higher, and the deceleration time of mitral inflow was shorter in group 3 than in group 2 (93 vs. 22% p &lt; 0.05, 95 vs. 1% p &lt; 0.05, and median 167 vs. 223 ms p &lt; 0.05, respectively). Group 4 was characterized by older age (median 85 years) and had a high systolic pulmonary arterial pressure (median 37 mmHg), less-distensible right ventricle (89%) and renal dysfunction (median 54 ml/min/1.73 m2). Compared with group 1, group 4 exhibited the highest risk of the cardiac events (hazard ratio [HR]: 19; 95% confidence interval [CI] 8.9–41); group 2 and 3 demonstrated similar rates of cardiac events (group 2 HR: 5.1; 95% CI 2.2–12; group 3 HR: 3.7; 95%CI, 1.3–10). The event-free rates were the lowest in group 4 (p for trend &lt; 0.001).Conclusions: K-means clustering divided HFpEF into 4 groups. Older patients with HFpEF may suffer from complication of RV afterload mismatch and renal dysfunction. Our study may be useful for stratified medicine for HFpEF.

ID: 10: FRAGMENTED QRS DOES NOT PREDICT ONSET OF HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PATIENTS WITH DIASTOLIC DYSFUNCTION

2016 ◽  
Vol 64 (4) ◽  
pp. 922.1-922 ◽  
Author(s):  
I Karagodin ◽  
JL Strande ◽  
B Marong
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Adverse Outcomes ◽  
Preserved Ejection Fraction ◽  
Bundle Branch Block ◽  
Fragmented Qrs ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

BackgroundDepolarization and repolarization ECG abnormalities such as fragmented QRS and wide frontal QRS-T angles are associated with heart failure with preserved ejection fraction (HFpEF) and are associated with adverse outcomes. However, no studies have investigated whether these abnormalities are present in asymptomatic diastolic dysfunction and whether these abnormalities are predictive of the development of HFpEF in subjects with diastolic dysfunction. The goal of this study is to determine whether fQRS and widening of the QRS-T angle precedes the development of HFpEF in patients with diastolic dysfunction.MethodsThis retrospective cohort study included 100 subjects with diastolic dysfunction and an ejection fraction >50% as reported on transthoracic echocardiography (TTE) who were free of HF at baseline. We analyzed 12-lead ECGs to determine fQRS and frontal QRS-T angle. Patients with QRS>120 ms, bundle branch block pattern, or incomplete right bundle branch block were excluded. The subjects were divided into two groups: Group 1 (n=53) included subjects who were known to progress to HFpEF and Group 2 (n=47) included patients who remained asymptomatic.ResultsThere was no significant difference in the proportion of patients with fQRS in Group 1 compared to Group 2 (33/41 vs. 35/42, p=0.78). The difference was also not significant when comparing hypertensive patients in Group 1 versus Group 2 (28/35 vs. 24/30, p=1.0), as well as patients without hypertension in both groups (5/6 vs. 11/12, p=1.0). On average, the QRS-T angle was wider in Group 1 (64.6) compared to Group 2 (51.7).ConclusionIn patients with asymptomatic diastolic dysfunction, fragmented QRS is present in both patients who progress to HFpEF as well as patients who remain asymptomatic. This suggests that fragmented QRS is associated with diastolic dysfunction, but does not predict the development of heart failure symptoms. The frontal QRS-T angle may be a useful measurement in predicting which patients go on to develop HFpEF. However, larger prospective studies are needed to further investigate this relationship.

scholarly journals The E/e’ Ratio—Role in Risk Stratification of Acute Heart Failure with Preserved Ejection Fraction

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 375
Author(s):  
Marilena-Brîndușa Zamfirescu ◽  
Liviu-Nicolae Ghilencea ◽  
Mihaela-Roxana Popescu ◽  
Gabriel Cristian Bejan ◽  
Sean Martin Maher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Independent Predictor ◽  
Secondary Outcome ◽  
Study Cohort ◽  
Management Problem ◽  
Preserved Ejection Fraction ◽  
All Cause Mortality ◽  
Group 2 ◽  
Group 1

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio < 13.80 (n = 39) and group 2 with an E/e’ ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio.

Worsening Renal Function during Index Hospitalization Does Not Predict Prognosis in Heart Failure with Preserved Ejection Fraction Patients

Cardiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Ravi Rasalingam ◽  
Rachel Parker ◽  
Katherine E. Kurgansky ◽  
Luc Djousse ◽  
David Gagnon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Incidence Density ◽  
Preserved Ejection Fraction ◽  
Index Hospitalization ◽  
Risk Of Death ◽  
Worsening Renal Function ◽  
Group 1

<b><i>Introduction:</i></b> Worsening renal function (WRF) predicts poor prognosis in patients with left ventricular systolic dysfunction. The effect of WRF in heart failure with preserved ejection fraction (HFpEF) is unclear. <b><i>Objective:</i></b> The objective of this study was to determine whether WRF during index hospitalization for HFpEF is associated with increased death or readmission for heart failure. <b><i>Methods:</i></b> National Veterans Affairs electronic medical data recorded between January 1, 2002, and December 31, 2014, were screened to identify index hospitalizations for HFpEF using an iterative algorithm. Patients were divided into 3 groups based on changes in serum Cr (sCr) during this admission. WRF was defined as a rise in sCr ≥0.3 mg/dL. Group 1 had no evidence of WRF, group 2 had transient WRF, and group 3 had persistent WRF at the time of discharge. <b><i>Results:</i></b> A total of 10,902 patients with index hospitalizations for HFpEF were identified (mean age 72, 97% male). Twenty-nine percent had WRF during this hospital admission, with 48% showing recovery of sCr and 52% with no recovery at discharge. The mortality rate over a mean follow-up duration of 3.26 years was 72%. Compared to group 1, groups 2 and 3 showed no significant difference in risk of death from any cause (hazard ratio [HR] = 0.95 [95% confidence interval [CI]: 0.87, 1.03] and 1.02 [95% CI: 0.93, 1.11], respectively), days hospitalized for any cause (incidence density ratio [IDR] = 1.01 [95% CI: 0.92, 1.11] and 1.01 [95% CI: 0.93, 1.11], respectively), or days hospitalized for heart failure (IDR = 0.94 [95% CI: 0.80, 1.10] and 0.94 [95% CI: 0.81, 1.09], respectively) in analyses adjusted for covariates affecting renal function and outcomes. <b><i>Conclusions:</i></b> While there is a high incidence of WRF during index hospitalizations for HFpEF, WRF is not associated with an increased risk of death or hospitalization. This suggests that WRF alone should not influence decisions regarding heart failure management.

scholarly journals Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

2021 ◽  
Vol 24 (4) ◽  
pp. 304-314
Author(s):  
M. A. Manukyan ◽  
A. Y. Falkovskaya ◽  
V. F. Mordovin ◽  
T. R. Ryabova ◽  
I. V. Zyubanova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Blood Pressure ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Resistant Hypertension ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Heat Map ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.

scholarly journals P1236EFFECTS OF SACUBITRIL-VALSARTAN IN HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PATIENTS UNDERGOING PERITONEAL DIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sha Fu ◽  
Zhenjian Xu ◽  
Baojuan Lin ◽  
Junzhe Chen ◽  
Qiuyan Huang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Peritoneal Dialysis ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Matched Pair ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Nyha Classification ◽  
Neprilysin Inhibitor

Abstract Background and Aims Angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril–valsartan is a landmark drug in heart failure with reduced ejection fraction (HFrEF), however, it remains unclear in patients with heart failure with preserved ejection fraction (HFpEF), especially the data of ARNI treatment on peritoneal dialysis (PD) patients with HFpEF are lacking. The present study was designed to determine the efficacy and safety of sacubitril–valsartan in patients with HFpEF undergoing peritoneal dialysis. Method We assigned end stage renal disease (ESRD)patients, receiving peritoneal dialysis for 3 months, with New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≥ 50%, and elevated level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) to receive sacubitril/valsartan treatment. Patients were regularly followed up after medication treatment. Wilcoxon matched-pair signed-rank (2 samples) tests were applied to investigate the alterations in Clinical and biochemical parameters as the efficacy before and after taking sacubitril–valsartan, and safety was also assessed. Results Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels (p=0.002) and heart rate (p=0.031) were markedly decreased after treatment with sacubitril/valsartan, signs and symptoms of heart failure (21/21 versus 15/21, p=0.021) and NYHA classification were notably improved after 3-12 months follow-up. Conclusion The present data suggested that sacubitril/valsartan treatment in the patients with HFpEF undergoing peritoneal dialysis was effective and safe, which is the first study about sacubitril/valsartan treatment for the PD patients with HFpEF, and it may bring the hope for these patients due to no other effective methods at present.

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