Effects of bisoprolol on heart rate variability in heart failure

doi:10.1016/S0002-9149(97)89316-2

The American Journal of Cardiology

Volume 77, Issue 8, 15 March 1996, Pages 612-617

https://doi.org/10.1016/S0002-9149(97)89316-2 Get rights and content

Abstract

Analysis of heart rate variability (HRV) provides a noninvasive index of autonomic nervous system activity. HRV has been shown to be reduced in heart failure. Preliminary data indicate that β blockers improve clinical status in patients with heart failure, but HRV improvement remains to be demonstrated. Fifty-four patients from the randomized double-blind, placebo-controlled Cardiac Insufficiency Bisoprolol Study were included in the HRV study. The bisoprolol daily dose was 5 mg once daily. We assessed HRV during 24-hour Hotter recordings before randomization and after 2 months of treatment. HRV was measured in the time domain by rootmean-square successive differences (rMSSD), the percentage of adjacent RR differences >50 ms (pNN50), and the SD of RR intervals (SDNN), and in the frequency domain by high-frequency (0.16 to 0.40 Hz) and low-frequency (0.04 to 0.15 Hz) power. Most patients were in New York Heart Association functional class III. The mean left ventricular ejection fraction was 27 ± 7%, and heart failure was idiopathic or ischemic. After 2 months, the patients receiving bisoprolol had a reduced mean heart rate compared with that in placebo patients (p = 0.0004). Bisoprolol increased 24-hour rMSSD (p = 0.04) and 24-hour pNN50 (p = 0.04), daytime SDNN (p = 0.05), and daytime high-frequency power (p = 0.03) power. Bisoprolol induced a significant increase in HRV parameters related to parasympathetic activity in heart failure. Increased vagal tone may contribute to the protective effect of β blockers and may have prognostic implications.

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Cardiac autonomic neuropathy (CAN) is a serious complication of type 1 and type 2 diabetes and is independently associated with major cardiovascular events, morbidity, and mortality. This narrative review examines the epidemiology, pathophysiology, and management and identifies areas of future research to address the challenge posed by CAN.
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Epidemiologic data indicate a varied prevalence of CAN in type 1 and 2 diabetes, with prevalences of 17% to 73%) depending on clinical and demographic factors. Indeed, duration of diabetes and hyperglycemia are the strongest risk factors for CAN development in type 1 diabetes. However, in type 2 diabetes, multifactorial risk factors, including obesity, hypertension, and hyperlipidemia, are associated with the development of CAN. Insulin resistance, which underpins type 2 diabetes and metabolic syndrome, has a direct role in the pathogenesis of CAN. Lifestyle interventions, including dietary measures and tailored exercise programs, have been beneficial in improving cardiac autonomic function primarily measured through heart rate variability. In addition, weight loss through bariatric surgery also improves heart rate variability and may prevent or reduce CAN progression in people living with obesity and concomitant type 2 diabetes. For optimization in type 2 diabetes, both lifestyle and targeted pharmacologic interventions are required to achieve glycemic/metabolic targets, and weight loss is required to prevent or reverse early CAN or prevent the progression to definite and severe CAN.
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Cardiovascular autonomic neuropathy (CAN) is a common and deadly complication of diabetes mellitus, which is frequently overlooked in clinical practice due to its characteristic subtle presentation earlier in disease. Yet, timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including cardiovascular disease (CVD), cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure and all-cause mortality. This review highlights current CAN epidemiology trends, novel mechanisms linking CAN with other diabetes complications and current recommendations for diagnosis and management of the disease in the clinical setting.
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Citation Excerpt :
Application of our analysis revealed reductions in HF specific to myocardial injury strongly suggesting involvement of a parasympathetic component19 that may otherwise not have been revealed with the conventional parameters. The confounding influences of co-morbidities38,39 and cardiac medications40 are potential limitations. However, the design of the study mitigated potential confounding factors, as each patient served as their own control.
Myocardial injury is more frequent after noncardiac surgery in patients with preoperative cardiac vagal dysfunction, as quantified by delayed heart rate (HR) recovery after cessation of cardiopulmonary exercise testing. We hypothesised that serial and dynamic measures of cardiac vagal activity are also associated with myocardial injury after noncardiac surgery.
Serial autonomic measurements were made before and after surgery in patients undergoing elective noncardiac surgery. Cardiac vagal activity was quantified by HR variability and HR recovery after orthostatic challenge (supine to sitting). Revised cardiac risk index (RCRI) was calculated for each patient. The primary outcome was myocardial injury (high-sensitivity troponin ≥15 ng L⁻¹) within 48 h of surgery, masked to investigators. The exposure of interest was cardiac vagal activity (high-frequency power spectral analysis [HF_Ln]) and HR recovery 90 s from peak HR after the orthostatic challenge.
Myocardial injury occurred in 48/189 (25%) patients, in whom 41/48 (85%) RCRI was <2. In patients with myocardial injury, vagal activity (HF_Ln) declined from 5.15 (95% confidence interval [CI]: 4.58–5.72) before surgery to 4.33 (95% CI: 3.76–4.90; P<0.001) 24 h after surgery. In patients who remained free of myocardial injury, HF_Ln did not change (4.95 [95% CI: 4.64–5.26] before surgery vs 4.76 [95% CI: 4.44–5.08] after surgery). Before and after surgery, the orthostatic HR recovery was slower in patients with myocardial injury (5 beats min⁻¹ [95% CI: 3–7]), compared with HR recovery in patients who remained free of myocardial injury (10 beats min⁻¹ [95% CI: 7–12]; P=0.02).
Serial HR measures indicating loss of cardiac vagal activity are associated with perioperative myocardial injury in lower-risk patients undergoing noncardiac surgery.
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Citation Excerpt :
A SDNN of between 50 and 100 ms was related to an annual mortality of 12.7% compared to a mortality of 5.5% in patients with a SDNN > 100 ms [31]. The HRV sub-study of CIBIS (Cardiac Insufficiency BIsoprolol Study) showed that β-blockers improve HRV and in particular those markers that reflect the PNS [32]. Unfortunately, many of these trials are from the 1990s and their findings in patients with ischaemic cardiomyopathy may not be directly transferable in the contemporary era of revascularisation.
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Effects of bisoprolol on heart rate variability in heart failure

Abstract

Am J Cardiol

Am J Cardiol

Am J Cardiol

Lancet

Am Heart J

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Metoprolol induced reduction in postinfarction mortality: pooled results from five double-blind randomized trials

Eur Heart J