Role of Adrenaline and Procainamide Infusion in the Evaluation of Unexplained Cardiac Arrest
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Synopsis: Provocative testing with adrenaline and procainamide infusions is useful in unmasking the etiology of apparent unexplained cardiac arrest.
Source: Krahn AD, et al. Diagnosis of Unexplained Cardiac Arrest: Role of Adrenaline and Procainamide Infusion. Circulation. 2005;112:2228-2234.
Krahn and colleagues from London, Ontario, Canada performed a long-term study on the value of provocative drug infusions in selected survivors of unexplained cardiac arrest and their family members. Survivors of a cardiac arrest were eligible for the study if they had experienced a cardiac arrest or syncope with documented ventricular tachycardia or ventricular fibrillation. Patients who had any evidence of left ventricular dysfunction, coronary artery disease, or anomalies, manifest long QT syndrome or reversible cardiac causes of cardiac death were excluded. First degree relatives of unexplained cardiac arrest were recruited and offered a similar testing protocol.
The testing protocol included a clinical assessment, an electrocardiogram, a treadmill exercise test, an echocardiogram, a cardiac MRI, and coronary angiography. If the cardiac arrest remained unexplained after these studies, the patients then underwent provocative adrenaline (epinephrine) and procainamide infusions. The adrenaline test was performed using escalating doses from 0.05 mcg per kg per minute to 0.40 mcg per kg per minute. Twelve lead electrocardiograms were monitored. The infusion was discontinued for either severe systolic hypotension (< 80 mmHg) or hypertension (> 200 mmHg), or when ventricular arrhythmias were noted. The following ventricular arrhythmias during the adrenaline infusion were considered significant: nonsustained ventricular tachycardia, greater than 10 premature beats per minute, or previously absent T wave alternans. QTc prolongation was considered significant if the QTc interval prolonged by greater than or equal to 65 msec above control levels.
If the response during the adrenaline test was negative, patients received a procainamide infusion after a 30 minute recovery period. This protocol involved a 30 minute infusion of 15 mg per kg (maximum 1000 mg) over 30 minutes. Electrocardiograms were monitored for ST segment elevation in the precordial leads, and changes were characterized as either saddleback or coved and considered positive for the Brugada syndrome according to established criteria. In patients with a positive ST segment response, isoproterenol was infused at a dose of 2 mcg per minute to see if the ST segment changes were reversible.
During follow-up, all the unexplained cardiac arrest survivors received an ICD. Patients with a clinical phenotype suggestive of catecholaminergic polymorphic ventricular tachycardia (CPVT) also received beta adrenergic blockers. Asymptomatic family members with positive test results suggestive of CPVT were also offered beta blockers.
The proband study group included 18 survivors of unexplained cardiac arrest or syncope with documented polymorphic ventricular tachycardia. Fifty-five family members of these patients also underwent the noninvasive testing protocol outlined above. These fifty-five family members included 8 patients (7 from a single CVPT family) with symptoms of either syncope or palpitations. The remaining 47 patients were had no symptoms of arrhythmia.
During exercise testing, 7 patients with unexplained cardiac arrest developed ventricular arrhythmias. Adrenaline infusion elicited a positive response in 9 patients. Procainamide infusion unmasked latent Brugada syndrome in 2 patients. Although the QTc interval was increased by both adrenaline and procainamide infusions, no patient had a QTc prolongation greater than 65 m/sec.
Based on exercise testing and drug infusions, the final diagnosis among the 18 unexplained cardiac arrest survivors was CPVT in 10 patients (56%), Brugada syndrome in 2 (11%), and idiopathic ventricular fibrillation in 6 (33%). Testing results in family members were less frequently positive. Among the 8 symptomatic patients, symptomatic polymorphic ventricular ectopy was observed during exercise testing in 7 patients from a single family and in one additional patient. One of 47 asymptomatic family members had similar findings. Two patients who had negative tests initially were retested subsequently after they developed symptoms. Both patients manifest previously absent polymorphic ventricular ectopy, similar to that observed in their proband mother, during repeat testing.
During follow-up, beta adrenergic blockade was not completely effective in CPVT patients. Four of 10 cardiac arrest survivors with CPVT and one previously symptomatic CPVT patient without cardiac arrest received appropriate ICD shocks despite antiadrenergic therapy.
Krahn et al conclude that provocative testing with adrenaline and procainamide is useful for unmasking the etiology of previously unexplained cardiac arrest. Following the same provocative but noninvasive testing protocol in symptomatic and asymptomatic family members provides an opportunity for identifying those at highest risk.
Commentary
Inherited and previously undiagnosed electrophysiologic disorders are a common underlying cause of unexplained cardiac arrest in patients without known structural heart disease. In some patients, these electrophysiologic abnormalities are readily detected on the baseline electrocardiogram. Patients with the Wolff-Parkinson-White syndrome and many patients with either a congenital long QT syndrome or the Brugada syndrome can often be identified based on their resting electrocardiogram. In other patients, however, and in many family members of individuals known to be affected, diagnostic electrocardiographic findings are either not visible at baseline or are present only intermittently. In symptomatic relatives without documented arrhythmias and in asymptomatic family members, testing would be helpful to identify those who are at risk and would be likely to benefit from therapy.
For some patients, genetic testing may be helpful in identifying latent disease in asymptomatic individuals. A commercial test for the recognized long QT syndrome mutations is available but expensive and may not be covered by payors. In addition, all the genes responsible for inherited arrhythmias have not been identified. Therefore, methods to detect the disorder in asymptomatic family members should be of clinical value.
In this paper, Krahn et al report on the yield of adrenaline and procainamide infusions. Adrenaline was shown to be useful in making the presumptive diagnosis of catecholaminergic polymorphic ventricular tachycardia. This is a relatively rare condition but one that is not associated with ECG findings at rest yet can be devastating. CPVT has been associated with mutations in the ryanodine type II receptor and in calsequestrin but other mechanisms may also be involved. Although the numbers are small, the paper confirms the usefulness of procainamide infusions in the Brugada syndrome. This syndrome has been associated with a mutation in the sodium channel gene SCN5A but many patients with this ECG pattern do not have any of the previously described genotypes.
In summary, the approach outlined in this paper seems a reasonable one for evaluating patients with cardiac arrest that remain unexplained after the initial evaluation. In particular, the test may be useful for identifying potentially life-threatening mutations in asymptomatic family members in whom early intervention can be justified.
Provocative testing with adrenaline and procainamide infusions is useful in unmasking the etiology of apparent unexplained cardiac arrest.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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