Author + information
- Barry J. Maron, MD⁎ (, )
- Martin S. Maron, MD,
- Bradley A. Maron, MD,
- Tammy S. Haas, RN,
- Robert K. Altman, MD,
- Stephen J. Smalley, MD,
- Joseph J. Doerer, MD,
- Mark S. Link, MD and
- Michael R. Mooney, MD
- ↵⁎Minneapolis Heart Institute Foundation, Hypertrophic Cardiomyopathy Center, 920 E. 28th Street, Suite 620, Minneapolis, Minnesota 55407
To the Editor:
Therapeutic hypothermia has been promoted as an effective strategy for the preservation of life and neuroprotection in unconscious survivors of out-of-hospital cardiac arrest (1–3), largely in patients age >50 years with myocardial infarction, stroke, acute encephalopathy, near drowning, or head injuries. Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease and the most frequent cause of youthful sudden cardiac death (4,5), which is associated with poor outcomes after cardiac arrest (4). We report our experience with cardiac arrest in HCM, demonstrating the efficacy of therapeutic hypothermia.
Databases of 2 HCM centers, the Minneapolis Heart Institute and Tufts Medical Center (2006 to 2010), were assessed. Seven patients with out-of-hospital cardiac arrest treated with hypothermia constituted the study group (Table 1). Over the study period, no other patient with HCM from the participating institutions experienced cardiac arrest.
The 7 patients ranged in age from 31 to 76 years (median 47 years); each was asymptomatic, and 6 were men. Four patients had resting left ventricular outflow gradients of 45 to 70 mm Hg. Maximal left ventricular wall thickness on echocardiography ranged from 21 to 24 mm (mean 23 ± 1.5 mm). Hypertrophy was segmental, involving the anterior septum and contiguous free wall or the distal (apical) portion of the left ventricle (Patient #2). None had conventional sudden death risk markers sufficient to warrant prophylactic defibrillator implantation (5).
Cardiac events occurred while sedentary or with mild activity. Rhythms at collapse were ventricular fibrillation (n = 5), ventricular tachycardia deteriorating to ventricular fibrillation (n = 1), and asystole (n = 1; Patient #2). Bystanders (including the husband of Patient #4) and/or emergency medical technicians initiated cardiopulmonary resuscitation or defibrillation within 3 min in 6 patients and within 9 min in 1 (Patient #7). Patients #3, #4, and #7 received ice packs in the community hospital en route to the center. The time elapsed from collapse to spontaneous circulation ranged from 5 to 37 min (mean 19 min). Transport time from collapse to arrival at the hypothermia center ranged from 4 to 146 min (mean 72 min).
The Glasgow Coma Scale score (6) was 3 in each patient upon arrival at the hypothermia center, indicative of an unconscious state without meaningful or voluntary response. The time interval from arrival at the hospital to hypothermia initiation ranged from 7 to 204 min (mean 90 min). Elapsed time from collapse to hypothermia ranged from 34 to 244 min (mean 62 min).
Standard hypothermia protocols used an automated external cooling system circulating chilled water through hydrogel energy transfer pads in 6 patients (Arctic Sun Temperature Management System, Medivance, Inc., Louisville, Colorado) or the endovascular infusion of chilled, sterile saline (CoolGard 3000, Zoll Medical Corporation, Chelmsford, Massachusetts) in 1 (Patient #2). Core temperature was rapidly lowered and maintained over 24 to 29.2 h at 31.8 to 33.1°C, followed by rewarming at ≤0.5°C/h. Complications, present in 6 patients, were most commonly pneumonia (n = 5), bradyarrhythmias (n = 5), and pulmonary edema (n = 3).
Hospital stay ranged from 7 to 27 days (mean 15 days). A Cerebral Performance Category score (7) of 1 patient, indicative of normal cerebral function, was assigned to each patient at or shortly after discharge. All survived, to date, 12 to 58 months after collapse, and are asymptomatic.
Ejection fractions measured before and after cooling did not differ significantly (mean 61 ± 5% vs. 63 ± 12%, p = 0.68) and were normal in 6 of the 7 patients (range 60% to 75%); cooling had a negligible effect on cardiac index and blood pressure. Each patient received a secondary prevention defibrillator; 2 experienced device interventions for ventricular fibrillation 6 and 17 months after hypothermia (Patients #4 and #6) (5). Two patients carried double disease-causing sarcomere mutations (8): MyBPC3Gln998Glu and TNN13Arg145Trp (Patient #2) and MyBPC3Arg943Ter and TNN13Ser166Phe (Patient #5).
At present, there are virtually no data available regarding the efficacy of therapeutic cooling in relatively young patients with genetic heart diseases. We describe our recent experience with patients (median age 47 years) who incurred out-of-hospital ventricular fibrillation or asystole. Each received prompt cardiopulmonary resuscitation or defibrillation and was unconscious when hypothermia began, but experienced rapid and dramatic improvement without significant intellectual or neurologic deficit or impaired cardiac pump performance.
The prognosis of patients with HCM after cardiac arrest (without hypothermia) has been unfavorable, with death and/or neurologic deficit the predominant consequence despite cardiopulmonary resuscitation or defibrillation (4). Notably, hypothermia was successful in this study group despite left ventricular wall thicknesses exceeding 20 mm in all patients, outflow tract gradients ≥45 mm Hg in 4 patients, asystole as the initial rhythm in 1 patient, and a long delay (>4 h) in cooling implementation in 1 patient.
These favorable results are probably largely related to the initial rapid response, the patients' generally good health (and youthful ages in 6 patients), and normal systolic function before arrest. Indeed, the 100% survival of this select cohort exceeds that anticipated in the broader population of patients treated with hypothermia (ranging from 50% to 60%) (1,2), as well as in competitive athletes with HCM and cardiac arrest treated only with cardiopulmonary resuscitation and defibrillation (4).
None of our patients were considered candidates for prophylactic defibrillators because of the absence of conventional risk markers (5); notably, however, 2 had double-sarcomere mutations, which have been associated with severe disease expression (8).
This study opens a window to novel patient subgroups that may benefit, with respect to survival and neuroprotection, from therapeutic hypothermia. Our encouraging results could represent a paradigm shift with regard to out-of-hospital cardiac arrest in patients with HCM, and support the broader dissemination of hypothermia as a powerful treatment strategy.
Please note: This study was funded in part by a grant from the Hearst Foundations (New York, NY).
- American College of Cardiology Foundation
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