scholarly journals Spironolactone Use and Improved Outcomes in Patients With Heart Failure With Preserved Ejection Fraction With Resistant Hypertension

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Tetsuro Tsujimoto ◽  
Hiroshi Kajio
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Placebo Group ◽  
Ejection Fraction ◽  
Resistant Hypertension ◽  
Primary Outcome ◽  
Preserved Ejection Fraction ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Patients With Heart Failure

Background Resistant hypertension is a salt‐retaining condition possibly attributable to inappropriate aldosterone secretion. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. Patients with heart failure with preserved ejection fraction (HFpEF) with (n=1004) and without (n=2437) resistant hypertension were included. Resistant hypertension was defined as systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥80 mm Hg in a patient with hypertension, despite the concurrent use of a renin‐angiotensin system blocker (angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker), a calcium channel blocker, and a diuretic; or as those patients using ≥4 classes of antihypertensive medication. The primary outcome was a composite of cardiovascular death, aborted cardiac arrest, or heart failure hospitalization. We analyzed hazard ratios (HRs) for outcomes with 95% CIs in the spironolactone group and compared them with the placebo group using Cox proportional hazard models. The risk of primary outcome events in patients with HFpEF with resistant hypertension was significantly lower in the spironolactone group than in the placebo group (HR, 0.70; 95% CI, 0.53–0.91; P =0.009), whereas the risk of primary outcome events in patients with HFpEF without resistant hypertension was not significantly different between the 2 groups (HR, 1.00; 95% CI, 0.83–1.20; P =0.97). There was a significant interaction between spironolactone use and resistant hypertension ( P =0.03). Similar associations were also observed in patients with HFpEF from the Americas (United States, Canada, Brazil, and Argentina) only. Conclusions Spironolactone may be an effective add‐on medication for patients with HFpEF with resistant hypertension taking angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers, and diuretics.

Abstract 14922: Prognostic Value of Baseline BNP and NT-ProBNP and its Interaction With Spironolactone in Patients With Heart Failure and Preserved Ejection Fraction in the TOPCAT Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Inder S Anand ◽  
Scott D Solomon ◽  
Brian Claggett ◽  
Sanjiv J Shah ◽  
Eileen O’Meara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Cox Regression ◽  
Selection Criterion ◽  
Adverse Outcomes ◽  
Preserved Ejection Fraction ◽  
Patient Selection Criterion ◽  
Increased Risk ◽  
Patients With Heart Failure

Background: Plasma natriuretic peptides (NP) are helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) and predict adverse outcomes. Levels of NP beyond a certain cut-off level are often used as inclusion criteria in clinical trials to ensure that the patients have HF, and to select patients at higher risk. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. In the I-Preserve trial a benefit of irbesartan on all outcomes was only seen in HFpEF patients with low but not high NP levels. We hypothesized that in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, spironolactone might have a greater benefit in patients with lower NP levels. Methods and Results: BNP (n=468) or NT-proBNP (n=400) levels were available at baseline in 868 patients with HFpEF enrolled in the natriuretic peptide stratum (BNP ≥100 pg/mL or an NT- proBNP ≥360 pg/mL) of the TOPCAT trial. In a multi-variable Cox regression model, that included age, gender, region (Americas vs. Russia/Georgia), atrial fibrillation, diabetes, eGFR, BMI and heart rate, higher BNP or NT-proBNP as a continuous, standardized log-transformed variable or grouped by terciles (see Figure for BNP & NT-proBNP tercile values) was independently associated with an increased risk of the primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for heart failure (Figure-1). There was a significant interaction between the effect of spironolactone and baseline BNP or NT-proBNP terciles for the primary outcome (P=0.02, Figure-2), with greater benefit of the drug in the lower compared to higher NP terciles. Conclusions: The benefit of spironolactone in lower risk HFpEF patients may indicate effects of the drug on early, but not late higher-risk stage of the disease. These findings question the strategy of using elevated NP as a patient selection criterion in HFpEF trials.

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.

P322Inhibitors of the renin-angiotensin system in diabetic patients with heart failure with preserved ejection fraction treatment: impact of m235t polymorphism of angiotensinogen

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Medentseva ◽  
I S Rudyk ◽  
M M Udovychenko ◽  
I C Gasanov ◽  
D P Babichev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction ◽  
Angiotensin System ◽  
Patients With Heart Failure ◽  
Heart Failure Questionnaire ◽  
M235t Polymorphism

Abstract Background Inhibitors of the renin-angiotensin system plays an important role in chronic heart failure treatment. However, the impact of Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) on treatment efficacy in diabetic patients with heart failure with preserved preserved ejection fraction (HFpEF) depending on M235T polymorphism of ATG is still unknown. Aim To estimate the efficacy of ACE inhibitors and ARBs therapy in diabetic patient with HFpEF depending on the polymorphism of the M235T of the ATG gene. Methods A total of eighty-two patients (50 females and 32 males; mean age 62,9±8,1 years) with HFpEF and type 2 diabetes mellitus were examined. Sixty-two patients were carriers of 235T allele (MT+TT genotypes), 20 patients had MM genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. All patients were divided into 4 groups depending on genotypes taking Ramipril or Valsartan during 12 months. Clinical examination, 6 minute walking test, Minnesota Living with Heart Failure Questionnaire (MLHFQ) have been used. All statistical tests were 2-tailed and p<0,05 was considered statistically significant and performed in Statistica 10.0. Results It was not found the significant difference in efficacy of treatment using Valsartan or Ramipril in diabetic patients with genotype MM with HFpEF, whereas in the presence of the T allele of the polymorphism of the M235T ATG, use of valsartan was more effective. Table shows the dynamics of the investigated parameters. Dynamics of parametrs during treatment Parameters HFpEF and DM2T, TT or MT HFpEF and DM2T, MM Ramipril (n=22) Valsartan (n=21) Ramipril (n=10) Valsartan (n=10) Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment SBP, mm Hg 172.0 [157.2; 178.5] 150.0 [132.0; 152.0]* 165.0 [145.3; 174.2] 128.0 [126.0; 134.0]* 167,5 [152.5; 176.0] 140.0 [134.0; 142.0] 160,0 [144.0; 170.0] 146.0 [138.0; 150.0] DBP, mm Hg 98.0 [86.0; 104.0] 92.0 [80.0; 94.0]* 96.0 [82.0; 100.0] 86.0 [80.0; 88.0]* 102.0 [84.0; 106.0] 98.0 [84.0; 100.0] 99.0 [80.0; 100.0] 94.0 [80.0; 96.0] 6 min test, m 313,0 [226,7; 375,5] 320,0 [236,4; 384,6]* 342.5 [258.0; 393.7] 372,0 [262,7; 397,9]* 305.0 [190.5; 375.0] 315.0 [198.5; 384.0] 328.0 [295.0; 401.0] 342.0 [298.0; 410.0] MLHFQ 62,0 [50,0; 71,2] 56,0 [46,5; 68,4]* 61.5 [50.5; 71.5] 40.5 [36.5; 56.5]* 60.0 [47.0; 76.2] 54.0 [43.0; 70.0] 58.0 [49.5; 76.2] 58.0 [49.5; 76.2] Dispnea, % 100 90* 100 70* 100 90 100 80 Edema, % 68,1 54,5* 61,9 33,3* 50 40 60 60 SBP, systolic blood pressure; DBP, diastolic blood pressure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; statistically significant changes (p<0.05). Conclusion Use of Valsartan comparing to Ramipril in diabetic T allele carriers of M235T polymorphism of ATG with HFpEF was independently associated with more effective clinical signs of heart failure improvement, blood pressure decrease, quality of life according to the MLHFQ and physical activity tolerance increase.

P6257Low systolic blood pressure on admission as a predictor of outcome in octogenarian patients with heart failure and preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Tsuda ◽  
Y Kanzaki ◽  
D Maeda ◽  
K Akamatsu ◽  
S Nakayama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Elderly Patients ◽  
Cardiac Death ◽  
Preserved Ejection Fraction ◽  
Very Elderly ◽  
Patients With Heart Failure ◽  
Poor Outcomes

Abstract Background Heart failure (HF) is an epidemic in healthcare worldwide including Asia. It appears that HF will become more serious with aging of the population. The patients with heart failure and preserved ejection fraction (HFpEF) were older, more often female, and frequently have comorbidities including hypertension. However, lower systolic blood pressure (SBP) on admission is associated with poor outcomes in patients with HF. It remains unclear whether this association is similar in very elderly patients with HFpEF. Purpose To investigate clinical features and prognosis in octogenarian HFpEF subjects. Methods We analyzed 87 consecutive subjects aged 80 years or older who were hospitalized for acute decompensated HF with left ventricular ejection fraction (LVEF) ≥50% between 2015 and 2017. Clinical characteristics and a composite event of cardiac death and HF hospitalization were compared in two groups according to SBP cut-off of 140 mmHg on admission. Results The prevalence of lower SBP subjects (mean BP = 118 mmHg) and higher SBP (mean BP = 166 mmHg) subjects were 41.4% and 58.6%, respectively. Lower SBP subjects were more comorbid with atrial fibrillation (72.2 vs. 45.1%, p=0.01). In the lower SBP group, diuretics, mineralocorticoid receptor antagonists (MRA), beta-blockers and ACE inhibitors/ARBs were more commonly used than higher SBP group (Table). During the observational period (median = 1.0 year), lower SBP on admission was associated with a 2.65-fold [95% confidence interval (CI): 1.29–5.55, p=0.009] greater likelihood of experiencing the composite events of cardiac death and rehospitalization for HF (Figure). This observation was still consistent even after adjusting clinical demographics and comorbidity [hazard ratio = 2.95, 95% CI: 1.30–6.87, p=0.01]. Table 1 Lower SBP group (n=36) Higher SBP group (n=51) P-value Atrial fibrillation (%) 72.2 0.01 0.01 Loop diuretic (%) 97.1 83.7 0.08 MRA (%) 47.1 24.5 0.04 Beta-blocker (%) 52.9 44.9 0.51 ACE inhibitor/ARB (%) 59.2 29.4 0.01 Figure 1 Conclusions In octogenarian patients with acute decompensated HF and preserved LVEF, SBP on admission less than 140 mmHg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in very elderly patients with HFpEF.

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