Bezold-Jarisch reflex-mediated asystole during dobutamine stress testing: a case report.

BACKGROUND: The Bezold-Jarisch reflex (BJR) is a cardioinhibitory parasympathetic response to activation of ventricular mechanoreceptors, which can result in bradycardia, atrioventricular block, or asystole. This phenomenon has been triggered by acute myocardial ischaemia, intra-arterial nitroglycerine use, natriuretic peptides, and with exceptional rarity, in middle-aged women only, by dobutamine infusion during stress echocardiography. CASE
SUMMARY: We present the case of a 61-year-old woman who suffered a 5.1-s sinus pause during her 20 μg/kg/min infusion of dobutamine. Recovery was immediate following termination of dobutamine infusion. Concurrent echocardiography was normal, and subsequent cardiac catheterization and electrophysiologic study were normal. DISCUSSION: This is the fifth documented case of a severe BJR causing asystole during dobutamine infusion, which adds to the accumulating evidence supporting the benign nature of the condition.

The Bezold–Jarisch reflex (BJR) is a cardioinhibitory parasympathetic response to activation of ventricular mechanoreceptors, which can result in bradycardia, atrioventricular block, or asystole.

It can be triggered by acute myocardial ischaemia, intra-arterial nitroglycerine use, natriuretic peptides, and rarely, by dobutamine infusion during stress echocardiography.

Asystole caused by dobutamine-induced BJR is a benign condition; with return of normal cardiac rhythm seen on termination of the infusion.

Introduction

The Bezold–Jarisch reflex (BJR) is a cardioinhibitory parasympathetic response to activation of ventricular mechanoreceptors, which can result in bradycardia, atrioventricular block, or asystole, associated with hypotension, decreased inotropy, and coronary vasodilation. The clinical manifestations of BJR are infrequently recognized yet lead to devastating outcome. This phenomenon has been triggered by acute myocardial ischaemia, intra-arterial nitroglycerine use, natriuretic peptides, and with exceptional rarity, in middle-aged women only, by dobutamine infusion during stress echocardiography.

Case presentation

A 61-year-old South Asian female with past medical history of hypertension, hyperlipidaemia, diabetes mellitus complicated by neuropathy, and gastroesophageal reflux disease presented to the emergency department for atypical angina associated with palpitations, dizziness, decreased exercise tolerance, and dyspnoea on exertion. On examination she was overweight, breathing comfortably on room air at rest, cardiac exam was normal, and there was no jugular venous distension. Given her risk factors, the patient was considered to have intermediate pretest probability for coronary artery disease. She was admitted as an inpatient and an acute coronary syndrome was excluded by serial negative cardiac enzymes and normal electrocardiogram (ECG). She was therefore referred for dobutamine stress echocardiography.

Rest ECG demonstrated normal sinus rhythm (). Baseline heart rate (HR) 65 b.p.m., systolic blood pressure (SBP) 120 mmHg, diastolic blood pressure (DBP) 80 mmHg, asymptomatic (). Baseline echocardiogram demonstrated normal cardiac wall motion, normal left ventricular size and systolic function, and an estimated ejection fraction of 65%. Dobutamine infusion was begun at 10 μg/kg/min, with increase in HR to 93 b.p.m. accompanied by SBP 137, DBP 73 without electrocardiographic changes. Dobutamine infusion rate was increased to 20 μg/kg/min with reproduction of chest pain. Shortly after the start of 20 μg/kg/min infusion, ECG demonstrated asystole with a 5.1-s sinus arrest (). Examination was terminated. Following resolution of the sinus arrest, the patient developed brief sinus bradycardia followed by resumption of normal sinus rhythm (). Throughout the exam, maximal heart rate achieved was 114 b.p.m. (72% of maximal predicted HR). At peak stress, there remained no regional wall motion abnormalities, and there was a reduction in left ventricular rate an augmentation in left ventricular function. The stress echocardiogram was non-diagnostic, though diagnostic sensitivity was limited by suboptimal stress.

Table 1

Blood pressure and pulse rate recordings during exam compared with timing of infusions

Vital signs measurements
Stage	BP (mmHg)	HR (b.p.m.)	Time (MM:SS)
Preinfusion	120/80	65	00:00
Dose 1		69	02:34
Dose 1	137/73	93	03:34
Dose 1		91	04:34
Dose 2		70	05:34
Dose 2	201/96	83	06:34
Dose 2	181/85	107	07:34
Dose 3	181/85	109	07:59
Dose 3		42	08:19
Post-infusion		0	08:49
Post-infusion		45	09:12
Post-infusion		62	09:26
Post-infusion		69	09:41
Post-infusion	154/69	48	11:45
Post-infusion	176/72	68	20:50

Dose 1: 5 μg/kg/min, Dose 2: 10 μg/kg/min, Dose 3: 20 μg/kg/min.

HR, heart rate; BP, blood pressure.

(A) Resting electrocardiogram; (B) electrocardiogram during dobutamine infusion at 20 μg/kg/min.

(A) Electrocardiogram during dobutamine infusion at 20 μg/kg/min (continued); (B) post-resuscitation electrocardiogram.

Patient was subsequently referred for coronary angiography, which was normal (). An electrophysiology study was performed during the patient’s inpatient stay. The result was also normal, with mildly prolonged SnRT and normal atrioventricular nodal function. She then had a loop recorder implanted to record any further arrhythmia events 1 day after the asystole event. Patient was discharged without symptoms or sequelae. There was no follow-up as of 1 year after device placement, and remote monitoring did not reveal any events as of the last transmission 4 months after device placement.

(A) Right coronary angiography; (B) left coronary angiography; and (C) left anterior descending angiography.

Discussion

The BJR is an inhibitory reflex that results in hypotension, vasodilation, and bradycardia., It originates in cardiac sensory receptors which are responsive to both chemical and mechanical stimuli. Stimulation of the reflex increases parasympathetic activity via vagal afferents and decreases sympathetic outflow, causing bradycardia, hypotension, and vasodilation. Several offending agents have elicited this reflex. In 1867, the BJR was discovered in animal models using veratrum alkaloids. Since then, several other eliciting factors have been described in the literature, including neuraxial and regional anaesthesia.,

In our literature search, there have been four previously documented cases of BJR-mediated cardiovascular collapse during dobutamine stress testing.

In the first case, a 60-year-old woman presented with chest pain and a non-diagnostic exercise test. A dobutamine stress echocardiographic test was performed. During the 30 μg/kg/h infusion the patient was noted to have diffuse hypokinesia of the left ventricle. She was noted to have sinus arrest for 8 s, which responded to intravenous atropine. The patient returned back to her previous state before the exam and subsequently refused coronary angiography and electrophysiological evaluation.

In the second case, a 48-year-old woman was evaluated for chest pain after an equivocal exercise stress test. During the 40 μg/kg/h infusion she developed an idioventricular rhythm followed by asystole. This resolved with cardiac massage. Further echocardiographic, coronary angiography, and electrophysiologic studies were normal.

The third case of BJR-mediated asystole was in a 59-year-old woman with a positive treadmill test for ischaemia. She underwent a dobutamine stress echocardiography. During the 30 μg/kg/h infusion she was noted to have non-sustained ventricular tachycardia and bradycardia, ultimately progressing to asystole for 8.4 s. Intravenous atropine was given, and the patient’s heart rate returned to baseline. Further coronary angiography and echocardiogram were normal, and the patient was discharged

The last documented case, in 2015, describes a 60-year-old female who was referred for dobutamine stress echocardiography after complaints of exertional chest pain and an inconclusive exercise stress test done 1 month prior to presentation. During the stress echocardiography, shortly after the 20 μg/kg/h infusion she developed sinus arrhythmia, which progressed into asystole. Dobutamine infusion was stopped, chest compressions and intravenous atropine were given, resulting in return of sinus rhythm. An echocardiogram done immediately after resuscitation showed no apparent abnormalities, coronary angiography was normal.

The management of dobutamine-induced asystole in the cases described in this article was managed with abrupt cessation of dobutamine infusion, followed by adherence to resuscitative protocols put forth by the American Heart Association., In three of four cases, the patient received intravenous atropine, which is the recommended treatment for suspected asystole or bradycardia caused by cardioinhibitory reflexes.,,

In cases of dobutamine-induced asystole, evaluation by coronary angiography is key to ruling out inferior wall ischaemia, which can cause sinoatrial and atrioventricular nodal dysfunction. In the patients described in this article, the asystole resolved with prompt management, and further workup was not indicative of other aetiologies. Paradoxical sinus deceleration occurring during dobutamine infusion occurs in 8% of patients. Most commonly, it can be seen in patients with pre-existing coronary artery disease. However, it can occur in patients in the absence of ischaemia and other significant cardiovascular pathology, which suggests the presence of a cardioinhibitory reflex. In the cases described above, patients found to have asystole after dobutamine infusion usually had good baseline left ventricular function and an absence of myocardial ischaemia.

Conclusion

Dobutamine stress echocardiography is a commonly used and generally well-tolerated diagnostic modality for detection of cardiac ischaemia in suspected coronary artery disease. In a study of 3041 people, it was found that the BJR was elicited in only one patient. In the five cases described in this article, it is notable that these events have occurred in women aged 40–60. It is unclear as to the relationship between age- and gender-specific sensitivities to the BJR during dobutamine stress testing. It is also notable that these events occur during high-dose dobutamine infusion and resolve with cessation of dobutamine and administration of atropine. Sinus arrest during dobutamine stress echocardiography remains a rare entity, which continues to be benign.

Lead author biography

Nimrah Hossain is a PGY-3 Resident in Internal Medicine at NewYork-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York. She is going on to chief residency at a university hospital with aspirations in cardiology and special interest in cardiac electrophysiology.

Supplementary material

Supplementary material is available at European Heart Journal - Case Reports online.

Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance.

Conflict of interest: none declared.

Click here for additional data file.

Admission to inpatient service	Presented with atypical angina associated with palpitations, dizziness, decreased exercise tolerance, and dyspnoea on exertion; normal electrocardiogram (ECG)
Given intermediate pretest probability	Referred for dobutamine stress echocardiogram
Starting dobutamine stress echocardiogram at 10 μg/kg/min	No ECG changes
Dobutamine at 20 μg/kg/min	ECG demonstrated asystole with 5.1 s sinus arrest
Exam was terminated	Following resolution of the sinus arrest, the patient developed brief sinus bradycardia followed by resumption of normal sinus rhythm
Referred for coronary angiography	Normal coronary angiography
Referred for electrophysiology study	Normal study
Loop recorder implanted	To record any further arrhythmia events
No further events noted	4 months after the event
No follow-up for device interrogation	12 months after the event