scholarly journals Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF

2021 ◽  
Author(s):  
Bruce D. Nearing ◽  
Imad Libbus ◽  
Gerrard M. Carlson ◽  
Badri Amurthur ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Rate ◽  
Left Ventricular Ejection Fraction ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Heart Rate Recovery ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Intrinsic Heart Rate

Abstract Purpose Disturbed autonomic function is implicated in high mortality rates in heart failure patients. High-intensity vagus nerve stimulation therapy was shown to improve intrinsic heart rate recovery and left ventricular ejection fraction over a period of 1 year. Whether these beneficial effects are sustained across multiple years and are related to improved baroreceptor response was unknown. Methods All patients (n = 21) enrolled in the ANTHEM-HF clinical trial (NCT01823887, registered 4/3/2013) with 24 h ambulatory electrocardiograms at all time points and 54 normal subjects (PhysioNet database) were included. Intrinsic heart rate recovery, based on ~ 2000 spontaneous daily activity-induced heart rate acceleration/deceleration events per patient, was analyzed at screening and after 12, 24, and 36 months of chronic vagus nerve stimulation therapy (10 or 5 Hz, 250 μs pulse width, 18% duty cycle, maximum tolerable current amplitude). Results In response to chronic high-intensity vagus nerve stimulation (≥ 2.0 mA), intrinsic heart rate recovery (all time points, p < 0.0001), heart rate turbulence slope, an indicator of baroreceptor reflex gain (all, p ≤ 0.02), and left ventricular ejection fraction (all, p ≤ 0.04) were improved over screening at 12, 24, and 36 months. Intrinsic heart rate recovery and heart rate turbulence slope were inversely correlated at both screening (r = 0.67, p < 0.002) and 36 months (r = 0.78, p < 0.005). Conclusion This non-randomized study provides evidence of an association between improvement in intrinsic heart rate recovery and left ventricular ejection fraction during high-intensity vagus nerve stimulation for a period of ≥ 3 years. Correlated favorable effects on heart rate turbulence slope implicate enhanced baroreceptor function in response to chronic, continuously cyclic vagus nerve stimulation as a physiologic mechanism.

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.

scholarly journals Systolic left ventricular dysfunction in patients with clinically suspected myocarditis

2020 ◽  
Vol 17 (4) ◽  
pp. 452-460
Author(s):  
N. P. Mitkovskaya ◽  
E. M. Balysh ◽  
T. V. Statkevich ◽  
N. A. Ladygina ◽  
E. B. Petrova ◽  
...  
Keyword(s):  
Heart Rate ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Systolic Dysfunction ◽  
Ventricular Ejection Fraction

The aim of the study was to investigate the features of clinically suspected myocarditis complicated by the left ventricular systolic dysfunction development. 93 patients with clinically suspected myocarditis were examined. The average age was 36.63 ± 1.15 years. In 43.01 % of patients the disease was accompanied by a decrease in left ventricular systolic function. In the group of patients with left ventricular systolic dysfunction in comparison with those with preserved left ventricular ejection fraction, a significantly lower proportion of men (75 % versus 81 %, respectively, χ2 = 9.3, p < 0,01) and a higher average group age (40.7 ± 1.87 versus 33.6 ± 1.3 years, respectively, p <  0,01) were revealed. The course of the disease in patients with left ventricular systolic dysfunction was characterized by a more frequent development of rhythm disturbances (65 % versus 43.3 %, respectively, χ2  = 4.3, p  < 0,05) and a higher heart rate at admission (94.5 (75‒100) and 85 (70‒89) beats per minute, respectively, p = 0.006). The structural and functional state of the heart according to echocardiography in patients with a reduced left ventricular ejection fraction versus comparison group was characterized by larger heart chambers sizes, more pronounced violations of local left ventricular contractility, more frequent involvement of the right ventricle in the pathological process (56.3  % versus 22.2  %, respectively, χ2   =  6.4, p  < 0,05). The relationships between the left ventricular ejection fraction Весці Нацыянальнай акадэміі навук Беларусі. Серыя медыцынскіх навук. 2020. Т. 17, № 4. C. 452–460 453 and the patient’s age (r = ‒0.36), the value of the heart rate at admission (r = ‒0.32), the severity of heart failure at admission, the degree of impaired local contractility of the left ventricle, the degree of right ventricular function (TAPSE, r  =  0.58), the severity of myocardial fibrosis according to cardiovascular magnetic resonance imaging (r = ‒0.32) were revealed.

scholarly journals Importance of elevated heart rate in the very early phase of ST-segment elevation myocardial infarction: Results from the DANAMI-3 trial

2018 ◽  
Vol 8 (4) ◽  
pp. 318-328 ◽  
Author(s):  
Lars Nepper-Christensen ◽  
Jacob Lønborg ◽  
Kiril A Ahtarovski ◽  
Dan E Høfsten ◽  
Kasper Kyhl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Left Ventricular Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Elevated Heart Rate

Background: Elevated heart rate is associated with poor clinical outcome in patients with acute myocardial infarction. However, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention the importance of elevated heart rate in the very early phase remains unknown. We evaluated the impact of elevated heart rate in the very early pre-hospital phase of ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention on cardiovascular magnetic resonance markers of reperfusion success and clinical outcome. Methods: In this DANAMI-3 substudy, 1560 ST-segment elevation myocardial infarction patients in sinus rhythm without cardiogenic shock were included in the analyses of clinical outcome and 796 patients underwent cardiovascular magnetic resonance to evaluate area at risk, infarct size and left ventricular ejection fraction. Heart rate was assessed on the first electrocardiogram with ST-elevation (time of diagnosis). Results: Despite equal area at risk (33%±11 versus 36%±16, p=0.174) patients with a pre-hospital heart rate ⩾100 beats per minute developed larger infarcts (19% (interquartile range, 9–17) versus 11% (interquartile range, 10–28), p=0.001) and a lower left ventricular ejection fraction (54%±12 versus 58%±9, p=0.047). Pre-hospital heart rate ⩾100 beats per minute was independently associated with an increased risk of all-cause mortality and heart failure (hazard ratio 2.39 (95% confidence interval 1.58–3.62), p<0.001). Conclusions: Very early heart rate ⩾100 beats per minute in ST-segment elevation myocardial infarction was independently associated with larger infarct size, reduced left ventricular ejection fraction and an increased risk of all-cause mortality and heart failure, and thus serves as an easily obtainable and powerful tool to identify ST-segment elevation myocardial infarction patients at high risk.

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