scholarly journals 338 Autonomic function and hyper-adrenergic tone despite beta-blockers in chronic coronary syndrome with preserved ejection fraction: prevalence and related factors

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Antonio Italia ◽  
Davide Lazzeroni ◽  
Luca Moderato ◽  
Claudio Centorbi ◽  
Matteo Bini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Ejection Fraction ◽  
Carotid Artery Disease ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Related Factors ◽  
Ventricular Ejection Fraction ◽  
Coronary Syndrome ◽  
Artery Disease

Abstract Aims Autonomic dysfunction is a prevalent and independent risk factor for adverse cardiovascular events and mortality in chronic coronary syndrome (CCS). Beta-blockers (BB), directly inhibiting adrenergic receptors, have been associated with a significant reduction in mortality and/or cardiovascular events in patients with recent acute coronary syndrome (ACS) or in those with heart failure (HF) with reduced left ventricular ejection fraction (LV-EF); on the other hand, the protective benefit in CCS patients without prior ACS or HF is less well established and lacks placebo-controlled trials. The aim of the study was to investigate the prevalence of hyper-adrenergic tone in CCS with preserved LV-EF in patients with or without BB as well as to assess related factors of hyper-adrenergic tone despite BB. Methods A total of 165 consecutive CCS patients have been enrolled. Inclusion criteria were documented coronary artery disease and preserved left-ventricular ejection fraction (>50%). Exclusion criteria were: recent ACS (<6 months), HF symptoms (NYHA >1) and atrial fibrillation. According to Heart rate variability (HRV) guidelines, 5 min beat-to-beat analysis was performed in order to assess sympatho-vagal balance (without BB wash-out). Patients were then divided into in two groups: hyper adrenergic tone (LF/HF > 2.01) and normal adrenergic tone (LF/HF < 2.01). Moreover, patients with hyper-adrenergic tone despite BB were classified as ‘BB non-responders’ while patients with normal adrenergic tone as ‘BB responders’. Results Mean age was 64 ± 12 years and male gender was prevalent (75%). Patients treated with BB were 56% and the majority (96%) were treated with high selective. Overall hyper adrenergic tone (isolated or associated with blunted vagal tone) was found in 47% of CCS patients and no difference was found in the percentage of hyper-adrenergic tone between patients with or without beta-blockers (45% vs. 55% P = 0.716). Within the BB groups, 89% had heart rate at target (<70 b.p.m.), while only 11% showed heart rate not at target (>70 b.p.m.). Among the heart rate not at target 80% had hyper-adrenergic tone despite beta-blockers (non-responders); on the other hand, among the heart rate not at target hyper-adrenergic tone despite beta-blockers was found in 43%. No differences in types of BB (metoprolol vs. bisoprolol) between BB responders and non-responders was found (P = 0.714). Higher left atrial volume index (36 ± 8 vs. 42 ± 14; P = 0.029) and E/e’ ratio (an echocardiographic marker of high left ventricular filling pressure) (9.4 ± 2.1 vs. 7.4 ± 2.1; P = 0.038) were found in patients with hyper-adrenergic tone despite beta-blockers (non-responder). Moreover, a trend toward significance of higher Lown’s arrhythmic risk was found in non-responders (19% vs. 8%; P = 0.066) (Figure). Finally, Beta-blockers patients with bradycardia and hyper-adrenergic tone (non-responders) had higher prevalence of carotid artery disease (64% vs. 44%; P = 0.047), where baroreceptors are located. Conclusion The prevalence of hyper-adrenergic tone is high in CCS patients with preserved ejection fraction; about half of patients treated with beta-blockers had residual hyper-adrenergic tone (non-responders). Hyper-adrenergic tone in BB patients is higher in those with 24-h heart rate not at target (>70 b.p.m.), thereby suitable of BB titration, as well as in those with diastolic dysfunction or with carotid artery disease, where baroceptors are located.

scholarly journals Elevated heart rate in hypertension and coronary artery disease: risk factor or risk marker in patients with preserved left ventricular ejection fraction

2019 ◽  
Vol 25 (4) ◽  
pp. 389-406 ◽  
Author(s):  
E. V. Kokhan ◽  
G. K. Kiyakbaev ◽  
Z. D. Kobalava
Keyword(s):  
Coronary Artery Disease ◽  
Heart Rate ◽  
Coronary Artery ◽  
Ejection Fraction ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Positive Effects ◽  
Artery Disease

Numerous studies have demonstrated the negative prognostic value of tachycardia, both in the general population and in specific subgroups, including patients with coronary artery disease (CAD), arterial hypertension (HTN) and heart failure with preserved ejection fraction (HFpEF). In the latest edition of the European guidlines for the treatment of HTN the level of heart rate (HR) exceeding 80 beats per minute is highlighted as a separate independent predictor of adverse outcomes. However, the feasibility of pharmacological reduction of HR in patients with sinus rhythm is unclear. Unlike patients with reduced ejection fraction, in whom the positive effects of HR reduction are well established, the data on the effect of pharmacological HR reduction on the prognosis of patients with HTN, CAD and/or HFpEF are not so unambiguous. Some adverse effects of pharmacological correction of HR in such patients, which may be caused by a change in the aortic pressure waveform with its increase in late systole in the presence of left ventricular diastolic dysfunction, are discussed. The reviewed data underline the complexity of the problem of clinical and prognostic significance of increased HR and its correction in patients with HTN, stable CAD and/or HFpEF.

scholarly journals Beta-blocker use is associated with prevention of left ventricular remodeling in recovered dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Enzan ◽  
S Matsushima ◽  
T Ide ◽  
H Kaku ◽  
T Higo ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Beta Blocker ◽  
Primary Outcome ◽  
Protocol Analysis ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction

Abstract Background Withdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta-blockers can prevent deterioration of cardiac function in those patients. Purpose We examined the effect of beta-blockers on left ventricular ejection fraction (LVEF) in recovered DCM. Methods We analyzed the clinical personal records of DCM, a national database of Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40% and a current LVEF ≥40%. Patients with recovered DCM were divided into two groups according to the use of beta-blockers. The primary outcome was defined as a decrease in LVEF >10% at two years of follow-up. A one to one propensity case-matched analysis was used. A per-protocol analysis was also performed. Considering intra- and inter-observer variability of echocardiographic evaluations, we also examined outcomes by multivariable logistic regression model after changing the inclusion criteria as follows; (1) previous LVEF <40% and current LVEF ≥40%; (2) previous LVEF <35% and current LVEF ≥40%; (3) previous LVEF <30% and current LVEF ≥40%; (4) previous LVEF <40% and current LVEF ≥50%. Outcomes were also changed as (1) decrease in LVEF ≥5% (2) decrease in LVEF ≥10% (3) decrease in LVEF ≥15%. The analysis of outcomes by using combination of multiple imputation and inverse probability of treatment weighting was also conducted to assess the effects of missing data and selection bias attributable to propensity score matching on outcomes. Results From 2003 to 2014, 40,794 consecutive patients with DCM were screened. Out of 5,338 eligible patients, 4,078 received beta-blockers. Propensity score matching yielded 998 pairs. Mean age was 61.7 years and 1,497 (75.0%) was male. Mean LVEF was 49.1±8.1%. The primary outcome was observed less frequently in beta-blocker group than in no beta-blocker group (18.0% vs. 23.5%; odds ratio [OR] 0.72; 95% confidence interval [CI] 0.58–0.89; P=0.003). The prevalence of increases in LVDd (11.5% vs. 15.8%; OR 0.70; 95% CI 0.54–0.91; P=0.007) and LVDs (23.1% vs. 27.2%; OR 0.80; 95% CI 0.65–0.99; P=0.041) was also lower in the beta-blocker group. Similar results were obtained in per-protocol analysis. These results were robust to several sensitivity analyses. As a result of preventing a decrease in LVEF, the deterioration to HFrEF was also prevented by the use of beta-blocker (23.6% vs. 30.6%). Subgroup analysis demonstrated that beta-blocker prevented decrease in LVEF regardless of atrial fibrillation. Conclusion Use of beta-blocker was associated with prevention of decrease in left ventricular ejection fraction in patients with recovered DCM. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Health Sciences Research Grants from the Japanese Ministry of Health, Labour and Welfare (Comprehensive Research on Cardiovascular Diseases)

scholarly journals Differing effects of beta-blockers on long-term clinical outcomes following percutaneous coronary intervention between patients with mid-range and reduced left ventricular ejection fraction

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Shitara ◽  
Ryo Naito ◽  
Takatoshi Kasai ◽  
Hirohisa Endo ◽  
Hideki Wada ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Ejection Fraction ◽  
Clinical Outcomes ◽  
Beta Blockers ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Abstract Background The aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF). Methods Data were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40–49%) and 201 patients with rEF (EF < 40%) were identified. They were assigned to groups according to users and non-users of beta-blockers and effects of beta-blockers were assessed between mrEF and rEF patients, separately. The primary outcome was a composite of all-cause death and non-fatal acute coronary syndrome. Results The median follow-up period was 5.5 years in mrEF patients and 4.3 years in rEF patients. Cumulative event-free survival was significantly lower in the group with beta-blockers than in the group without beta-blockers in rEF (p = 0.003), whereas no difference was observed in mrEF (p = 0.137) between those with and without beta-blockers. In the multivariate analysis, use of beta-blockers was associated with reduction in clinical outcomes in patients with rEF (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36–0.97; p = 0.036), whereas no association was observed among those with mrEF (HR 0.74; 95% CI 0.49–1.10; p = 0.137). Conclusions Our observational study showed that use of beta-blockers was not associated with long-term clinical outcomes in IHD patients with mrEF, whereas a significant association was observed in those with rEF.

First clinical trial with etomoxir in patients with chronic congestive heart failure

2000 ◽  
Vol 99 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Stephan SCHMIDT-SCHWEDA ◽  
Christian HOLUBARSCH
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Sarcoplasmic Reticulum ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

In the failing human myocardium, both impaired calcium homoeostasis and alterations in the levels of contractile proteins have been observed, which may be responsible for reduced contractility as well as diastolic dysfunction. In addition, levels of a key protein in calcium cycling, i.e. the sarcoplasmic reticulum Ca2+-ATPase, and of the α-myosin heavy chain have been shown to be enhanced by treatment with etomoxir, a carnitine palmitoyltransferase inhibitor, in normal and pressure-overloaded rat myocardium. We therefore studied, for the first time, the influence of long-term oral application of etomoxir on cardiac function in patients with chronic heart failure. A dose of 80 mg of etomoxir was given once daily to 10 patients suffering from heart failure (NYHA functional class II–III; mean age 55±4 years; one patient with ischaemic heart disease and nine patients with dilated idiopathic cardiomyopathy; all male), in addition to standard therapy. The left ventricular ejection fraction was measured echocardiographically before and after a 3-month period of treatment. Central haemodynamics at rest and exercise (supine position bicycle) were defined by means of a pulmonary artery catheter and thermodilution. All 10 patients improved clinically; no patient had to stop taking the study medication because of side effects; and no patient died during the 3-month period. Maximum cardiac output during exercise increased from 9.72±1.25 l/min before to 13.44±1.50 l/min after treatment (P < 0.01); this increase was mainly due to an increased stroke volume [84±7 ml before and 109±9 ml after treatment (P < 0.01)]. Resting heart rate was slightly reduced (not statistically significant). During exercise, for any given heart rate, stroke volume was significantly enhanced (P < 0.05). The left ventricular ejection fraction increased significantly from 21.5±2.6% to 27.0±2.3% (P < 0.01). In acute studies, etomoxir showed neither a positive inotropic effect nor vasodilatory properties. Thus, although the results of this small pilot study are not placebo-controlled, all patients seem to have benefitted from etomoxir treatment. Etomoxir, which has no acute inotropic or vasodilatory properties and is thought to increase gene expression of the sarcoplasmic reticulum Ca2+-ATPase and the α-myosin heavy chain, improved clinical status, central haemodynamics at rest and during exercise, and left ventricular ejection fraction.

Abstract 13135: Starting Beta-blockers in Hypertension is Followed by Excess Loop Diuretic Use: Beta-blocker Induced Heart Failure?

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel N Silverman ◽  
Jeanne d de Lavallaz ◽  
Timothy B Plante ◽  
Margaret M Infeld ◽  
Markus Meyer
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Beta Blocker ◽  
Antihypertensive Medication ◽  
Temporal Relationship ◽  
Loop Diuretic ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Introduction: Recent investigation has identified that discontinuation of beta-blockers in subjects with normal left ventricular ejection fraction (LVEF) leads to a reduction in natriuretic peptide levels. We investigated whether a similar trend would be seen in a hypertension clinical trial cohort. Methods: In 9,012 subjects hypertensive subjects without a history of symptomatic heart failure, known LVEF <35% or recent heart failure hospitalization enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT), we compared incidence of loop diuretic initiation and time to initiation following start of a new anti-hypertensive medication. The categorical relationship (new antihypertensive class followed by loop-diuretic use) and temporal relationship (time to loop diuretic initiation) were each analyzed. The categorical relationship was assessed using a Pearson’s chi-squared test and the temporal relationship using a Wilcoxon rank sum test. Bonferroni-corrected p-values were utilized for all comparisons. Results: Among the 9,012 subjects analyzed, the incidence of anti-hypertensive initiation and loop diuretic initiation was greatest following start of a beta-blocker (16.6%) compared with other antihypertensive medication classes (calcium channel blocker 13.8%, angiotensin converting enzyme-inhibitor/angiotensin receptor blocker 12.9% and thiazide diuretic 10.2%; p<0.001). In addition, the median time between starting a new antihypertensive medication and loop diuretic was the shortest for beta-blockers and longest for thiazides (both p <0.01). No significant differences in renal function were identified between groups. Conclusion: Compared to other major classes of hypertensive agents, starting beta-blockers was associated with more common and earlier initiation of a loop diuretics in a population without heart failure at baseline. This finding may suggest beta-blocker induced heart failure in a population with a predominantly normal ejection fraction.

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