Inappropriate Heart Rate Research Articles

Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury.

Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53–64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51–71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (−7 (−9; −2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (−11 (−20; −2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients.

Optymalna rozbudowa dwujamowego układu stymulującego u pacjentki z utrwalonym migotaniem przedsionków

In patients with sick sinus syndrome, and previously implanted dual-chamber pacemaker, the occurrence of atrial fibrillation finally assessed as permanent is most commonly regarded as a natural course of the disease. The inappropriate heart rate control and right ventricular pacing can both negatively influence left ventricle mechanical performance leading to cardiomyopathy and heart failure. It was presented the case of a 72-year-old woman with permanent atrial fibrillation with narrow QRS complex, after dual-chamber pacemaker implantation, admitted to our department with signs and symptoms of acute decompensated congestive heart failure. The modification of pharmacotherapy allowed to compensate heart failure, however with only small influence on structural remodelling and patient’s symptoms. The successful upgrade of the pacing system to the direct His-bundle pacing enabled the restoration of proper function of the heart and full symptoms relief. The direct His-bundle pacing is an approach of choice in such a group of patients.

QT Interval Shortening After Bariatric Surgery Depends on the Applied Heart Rate Correction Equation.

A shortening of electrocardiographic QT interval has been observed in obese subjects after weight loss, but previous results may have been biased by inappropriate heart rate (HR) correction. Electrocardiography (ECG) recordings of 49 (35 females) severely obese patients before and 12months after Roux-en-Y gastric bypass (RYGB) surgery were analysed. QT interval (QTc) was calculated by using four different equations, i.e. Bazett, Fridericia, Framingham and Hodges. Irrespectively of the used correction formula, QTc interval length was reduced after the surgery (QTcBazett -31±18ms; QTcFridericia -12±15ms; QTcFramingham -14±15ms; QTcHodges -9±15ms; all Ps<0.001), but QTcBazett reduction was significantly greater than the reduction in QTc calculated upon the other three equations (all Ps<0.001). Moreover, changes in QTcBazett (P<0.001) but not in QTcFridericia, QTcFramingham and QTcHodges (all Ps>0.05) were significantly correlated with concurrent changes in HR. Multivariate regression analyses revealed a significant independent association of serum insulin levels with QTcFridericia, QTcFramingham and QTcHodges values (all Ps<0.05) preoperatively, whilst changes in QTc interval length after the surgery were not consistently associated to concurrent changes in metabolic traits. Our data show that the extent of weight loss-associated QTc interval shortening largely depends on the applied HR correction equation and appears to be overestimated when the most popular Bazett's equation is used.

The mitochondrial uniporter controls fight or flight heart rate increases.

Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant negative (DN) MCU. Here we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment prior to each heartbeat. Our findings show the MCU is necessary for complete physiological heart rate acceleration and suggest MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

Incessant tachycardia with borderline QRS duration, short HV interval, and left ventricular dysfunction: What is the mechanism?

a Q a t s T t f o s i m m v ( d Case report An 18-year-old man presented with palpitations of 10 days’ duration. Wide complex tachycardia with heart rate of 130– 180 beats/min and hypotension (systolic blood pressure 70 mm Hg) was noted. Cardioversion restored sinus rhythm, but wide complex tachycardia recurred on multiple occasions. He was intubated and treated with intravenous amiodarone and catecholamines. Bedside echocardiogram showed globally decreased left ventricular systolic function (left ventricular ejection fraction 30%–35%). Heart rhythm stabilized, and the patient was extubated 3 days later. He subsequently remained in sinus rhythm. Amiodarone was discontinued. Electrophysiologic study was performed, and no arrhythmia was induced. The patient was discharged off amiodarone with a wearable defibrillator. Repeat electrophysiologic study was performed 32 days after the initial presentation. At that time, the baseline electrocardiogram was normal, with QRS duration of 80 ms. No arrhythmia was induced despite aggressive right ventricular (RV) pacing and use of isoproterenol at dose up to 15 g/min. ual-chamber implantable cardioverter-defibrillator was imlanted. Implantable cardioverter-defibrillator interrogation 3 eeks later indicated inappropriate heart rate distribution with endency toward tachycardia. Runs of regular tachycardia lastng minutes to hours were noted. The tachycardia had a heart ate of 130 beats/min (slower than the programmed slow venricular tachycardia [VT] zone), with QRS duration of 114 ms, nferior axis, and left bundle branch block (LBBB) morpholgy. It was asymptomatic. Radiofrequency (RF) ablation was erformed the next day. During the procedure, the patient was n incessant tachycardia with HV interval of 11 ms and 1:1 VA elationship (Figure 1A). Overdrive pacing from high right

Biological Heart Rate Reduction Through Genetic Suppression of Gα(s) Protein in the Sinoatrial Node.

BackgroundElevated heart rate represents an independent risk factor for cardiovascular outcome in patients with heart disease. In the sinoatrial node, rate increase is mediated by β1 adrenoceptor mediated activation of the Gαs pathway. We hypothesized that genetic inactivation of the stimulatory Gαs protein in the sinoatrial node would provide sinus rate control and would prevent inappropriate heart rate acceleration during β-adrenergic activation.Methods and ResultsDomestic pigs (n=10) were evenly assigned to receive either Ad-small interfering RNA (siRNA)-Gαs gene therapy to inactivate Gαs or adenovirus encoding for green fluorescent protein (Ad-GFP) as control. Adenoviruses were applied through virus injection into the sinoatrial node followed by epicardial electroporation, and heart rates were evaluated for 7 days. Genetic inhibition of Gαs protein significantly reduced mean heart rates on day 7 by 16.5% compared with control animals (110±8.8 vs 131±9.4 beats per minute; P<0.01). On β-adrenergic stimulation with isoproterenol, we observed a tendency toward diminished rate response in the Ad-siRNA-Gαs group (Ad-siRNA-Gαs, +79.3%; Ad-GFP, +61.7%; n=3 animals per group; P= 0.294). Adverse effects of gene transfer on left ventricular ejection fraction (LVEF) were not detected following treatment (LVEFAd-siRNA-Gαs, 66%; LVEFAd-GFP, 60%).ConclusionsIn this preclinical proof-of-concept study targeted Ad-siRNA-Gαs gene therapy reduced heart rates during normal sinus rhythm compared with Ad-GFP treatment and prevented inappropriate rate increase after β-adrenergic stimulation. Gene therapy may provide an additional therapeutic option for heart rate reduction in cardiac disease. (J Am Heart Assoc. 2012;1:jah3-e000372 doi: 10.1161/JAHA.111.000372)

Sitcom Syncope: A Case Series and Literature Review of Gelastic (Laughter-Induced) Syncope

Syncope is a common complaint that is frequently evaluated without identifying a precipitating cause. Gelastic (laughter-induced) syncope is an uncommon and poorly understood condition. We describe 3 patients who experienced loss of consciousness during vigorous laughter. Each patient had an extensive medical evaluation, including a comprehensive history and physical examination, 12-lead electrocardiography, chest radiograph, routine blood analysis, polysomnography, tilt table testing, 2-dimensional transthoracic echocardiography, nuclear or echocardiographic stress testing, and 24-hour Holter monitoring. All 3 patients had an abnormal response to head-up tilt table testing, with either a significant decrease in systolic blood pressure or inappropriate heart rate response on achieving an upright position. These observations together with our review of the literature suggest that gelastic syncope may be a variant of vasodepressor syncope. Knowledge of this condition, its pathophysiology, and potential treatment options may be of value to clinicians when evaluating patients with unexplained loss of consciousness.

Optimised rate-responsive pacing does not improve either right ventricular haemodynamics or exercise capacity in adults with a systemic right ventricle

Inappropriate heart rate response to exercise - chronotropic incompetence - and exercise intolerance are common in patients with a systemic right ventricle. We aimed to assess the relationship between heart rate increase, oxygen consumption, and timing of the right ventricular cardiac cycle in this cohort. We prospectively studied nine patients with systemic right ventricles and pre-existing pacemakers using Doppler-echocardiography and treadmill exercise testing. Echocardiography was performed at increasing heart rates. Exercise tests were performed with baseline pacemaker settings and with optimised heart rate response in random order. In addition, eight age- and gender-matched controls underwent exercise testing using a similar exercise protocol. Patients with a systemic right ventricle had significantly lower peak oxygen consumption compared to controls - 12.6 plus or minus 6.8 versus 31.4 plus or minus 6.6 metres per kilogram per minute (p = 0.0006) - at baseline and active pacemaker reprogramming failed to increase peak oxygen consumption in this cohort - 12.6 plus or minus 6.8 versus 12.4 plus or minus 4.9 millilitres per kilogram per minute (p = NS) at baseline and with reprogramming, respectively. We found not only a marked increase in total isovolumic time but also a significant reduction in total filling time and the aortic velocity time integral, p-value is less than 0.001 for all, at higher heart rates compared to baseline conditions. This study suggests that despite chronotropic incompetence at baseline, rate-responsive pacing does not improve exercise capacity in patients with a systemic right ventricle. It further indicates that high heart rates may be detrimental in these patients by reducing diastolic filling and stroke volume. These findings may have clinical implications when considering implantation of a permanent pacemaker in this cohort.

Hemodynamic significance of heart rate in neurally mediated syncope

Vasovagal and vasodepressor syncope are used interchangeably in the literature to describe the common faint syndrome, now collectively named neurally mediated syncope. The significance of heart rate (HR) in these reflex-induced reactions remains unclear. The study was undertaken to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope. In all, 113 patients with syncope of unknown etiology were studied by head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15 women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for analysis. The hemodynamic data were compared between patients who developed bradycardia (vasovagal group, n = 15) and those without bradycardia (vasodepressor group, n = 20). The baseline hemodynamic data (mean +/- standard deviation) and the hemodynamic responses after 10-min headup tilt were similar between patients in the vasovagal and vasodepressor groups. During syncope, patients with vasovagal reaction developed hypotension and paradoxical bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor reaction developed a precipitous drop in arterial blood pressure with inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal syncope manifested a significantly lower cardiac index and a significantly higher systemic vascular resistance index than patients with vasodepressor syncope (1.47 +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353 dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients studied. These findings suggest that the hemodynamic characteristics of vasovagal and vasodepressor reactions are different, and that HR plays a significant role in neurally mediated syncope.

The cox maze III procedure: Parallel normalization of sinus node dysfunction, improvement of atrial function, and recovery of the cardiac autonomic nervous system

Objective: The Cox maze III procedure includes isolation of the pulmonary veins and multiple incisions in both atria in what corresponds to partial autotransplantation and partial denervation of the heart. The aim of this prospective longitudinal study was to identify physiologic effects of reinnervation on changes in heart rate at rest and in response to various stimulations and on atrial function after the Cox maze III procedure. Patients and methods: Power spectral analysis of heart rate variability, exercise testing, 24-hour Holter monitoring, electrocardiography, and transthoracic and transesophageal echocardiography were performed in 30 adult patients after the combined Cox maze III procedure and mitral valve surgery (maze group). They were prospectively followed up at 1, 3, 6, and 12 months after the operation. The results were compared with those of 15 heart transplant recipients (transplant group) and normal probands (healthy adults, n = 12). Results: The physiologic effects of denervation with no differences in cardiac autonomic activity between the groups were seen early after the operation. Later, evidence of autonomic reinnervation was observed only in the maze group but not in the transplant group. Inappropriate heart rate responses during physical exercise were clearly evident in both groups after 1 and 3 months, with progressive improvement seen between 6 and 12 months only in the maze group. Left atrial function after the Cox maze procedure improved parallel to the recovery of sinus node function. Conclusion: Progressive improvement of sinus node function and atrial contractions with significant functional normalization 1 year after the Cox maze procedure corresponded to functional reinnervation and recovery of the autonomic nervous system. (J Thorac Cardiovasc Surg 1999;118:287-96)

Efficacy of intravenous granisetron in suppressing the bradycardia and hypotension associated with a rabbit model of the Bezold-Jarisch reflex.

This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.

The child with recurrent syncope: Autonomic function testing and beta-adrenergic hypersensitivity

Recurrent syncope in the child with a normal heart poses both diagnostic and therapeutic problems. To assess autonomic contributions to syncope, formal autonomic function testing was performed in 22 children (aged 7 to 18 years) with recurrent syncope and a normal heart. Autonomic testing consisted of eight to nine separate tests; 14 of the 22 patients had reproduction of syncope or symptoms during testing.Patients with a positive test had a lower norepinephrine level while supine (334 ± 86 versus 547 ± 169 pg/ml, p < 0.01) and lower norepinephrine level in the upright position (628 ± 219 versus 891 ± 270 pg/ml, p < 0.05) than did patients with a negative test. The slope of heart rate response versus log isoproterenol dose was greater in patients with a positive test than in those with a negative test (1.70 ± 0.70 versus 0.89 ± 0.19, p < 0.01). All five patients with a positive test who were given intravenous propranolol had elimination of syncope with repeat testing. Eight of 10 patients with a positive test were successfully treated with atenolol, including 2 patients without prior resolution of symptoms alter pacemaker implantation for symptoms attributed to bradycardia.Beta-adrenergic hypersensitivity may cause recurrent syncope in young patients. Inappropriate heart rate response to standing may elicit the Bezold-Jarisch reflex, resulting in bradycardia or hypotension, or both, in some patients. Beta-adrenergic blockade is of benefit in many of these patients.

Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardlographic and hemodynamie responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at ≤7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at ≤3 μg/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 ± 16 mm Hg vs baseline 76 ± 10 mm Hg, p <0.001) and inappropriate heart rate slowing (mean heart rate, 59 ± 39 beats/min vs baseline 88 ± 18 beats/min, p <0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 ± 0.64 μg/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 μg/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 ± 7 min Hg vs tilt 10 min, 77 ± 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 ± 12 beats/min vs tilt 10 min, 83 ± 11 beats/min, difference not significant). Furthermore, during subsequent 20 ± 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.

Adverse effects due to morphine sulfate. Challenge to previous clinical doctrine

Despite a lack of clinical data in this area, conventional wisdom holds that morphine sulfate induces vagally mediated conduction defects, especially in patients with inferior myocardial infarction. To assess the accuracy of this “clinical pearl,” the records of 244 patients admitted to the Barnes Hospital Cardiac Care Unit with suspected acute myocardial infarction were reviewed to determine the frequency of deleterious cardiovascular effects related to the administration of morphine sulfate. Of 184 patients (156 subsequently documented to have infarction) who received morphine sulfate, four patients had symptomatic hypotension temporally associated with morphine sulfate administration. This represented a frequency of 2.2 percent for all patients treated with morphine sulfate and a frequency of 2.6 percent in those with proved infarction. In each instance, the heart rate response was inappropriate, i.e., decreased or less markedly accelerated than might be expected given the reduced blood pressure, suggesting a vagal mechanism for the adverse effects. Only one of the four patients had inferior infarction, and in three of four instances, the adverse effect occurred after the first dose. All patients subsequently received morphine sulfate without evidence of toxicity. No case of narcotic-induced conduction abnormality was identified. This series, which is the most extensive evaluation of the topic, documents that adverse cardiovascular effects due to morphine sulfate are rare and do not conform to preconceived clinical doctrine. They consist of inappropriate heart rate responses to hypotension rather than conduction defects and are not particularly associated with inferior myocardial infarction.