Effectiveness of Mild Therapeutic Hypothermia Following Cardiac Arrest in Adult Patients With Congenital Heart Disease

Accepted Manuscript Effectiveness of Mild Therapeutic Hypothermia Following Cardiac Arrest in Adult Patients with Congenital Heart Disease Michael N. Young, MD Ryan D. Hollenbeck, MD Jeremy S. Pollock, MD John A. McPherson, MD Joseph L. Fredi, MD Robert N. Piana, MD May L. Mah, MD Frank A. Fish, MD Larry Markham, MD PII:

S0002-9149(14)00969-2

DOI:

10.1016/j.amjcard.2014.04.012

Reference:

AJC 20414

To appear in:

The American Journal of Cardiology

Received Date: 17 February 2014 Revised Date:

7 April 2014

Accepted Date: 9 April 2014

Please cite this article as: Young MN, Hollenbeck RD, Pollock JS, McPherson JA, Fredi JL, Piana RN, Mah ML, Fish FA, Markham L, Effectiveness of Mild Therapeutic Hypothermia Following Cardiac Arrest in Adult Patients with Congenital Heart Disease, The American Journal of Cardiology (2014), doi: 10.1016/j.amjcard.2014.04.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Effectiveness of Mild Therapeutic Hypothermia Following Cardiac Arrest in Adult Patients with Congenital Heart Disease Michael N. Young, MDa*, Ryan D. Hollenbeck, MDa, Jeremy S. Pollock, MDa, John A.

RI PT

McPherson, MDa, Joseph L. Fredi, MDa, Robert N. Piana, MDa,c, May L. Mah, MDa,b,c, Frank A. Fish, MDb,c, Larry Markham, MDa,b,c

SC

Divisions of aCardiovascular Medicine, bPediatric Cardiology and cAdult Congenital

M AN U

Heart Disease, Vanderbilt University Medical Center, Nashville, Tennessee

*Corresponding author: Tel: (615) 322-2318; Fax: (615) 936-1872 Email address: [email protected] (M.N. Young)

Tennessee 37232-6300

TE D

Mailing address: 2220 Pierce Avenue, 383 Preston Research Building (PRB), Nashville,

AC C

EP

Short Title: Hypothermia in Adult Congenital Heart Disease

1

ACCEPTED MANUSCRIPT

Abstract: Mild therapeutic hypothermia (TH) is an established therapy to improve survival and reduce neurologic injury following cardiac arrest. Adult patients with congenital heart

RI PT

disease (ACHD) are at increased risk of sudden cardiac death. The use of TH in this population has not been extensively studied. The aim of this study is to report our

institutional experience using this treatment modality in ACHD patients following

SC

cardiac arrest. We performed a retrospective observational study of a cohort of 245

consecutive patients treated with TH following cardiac arrest from 2007 to 2013. Five

M AN U

patients were identified as having complex ACHD with a mean age of 28 years. All were treated with TH according to an institutional protocol utilizing active surface cooling to maintain a core body temperature of 32-34 degrees Celsius for 24 hours following cardiac arrest. Congenital lesions in these 5 patients included anomalous left coronary

TE D

artery from the pulmonary artery (ALCAPA); L-transposition of the great arteries (LTGA); D-transposition of the great arteries (D-TGA) status post atrial switch; unoperated tricuspid atresia, atrial septal defect (ASD) and ventricular septal defect (VSD) with

EP

Eisenmenger’s physiology; and surgically corrected ASD, cleft mitral valve and subaortic membrane. All 5 patients suffered cardiac arrest due to ventricular arrhythmia and all

AC C

survived to discharge without significant neurologic impairment. Therapeutic interventions included ALCAPA ligation, percutaneous coronary intervention and defibrillator implantation. In conclusion, in 5 patients with ACHD, the use of TH following cardiac arrest resulted in 100% survival to hospital discharge with good neurologic outcome post-resuscitation. Key Words: Adult congenital heart disease, therapeutic hypothermia, cardiac arrest

2

ACCEPTED MANUSCRIPT

Introduction: Cardiac arrest is a major public health concern associated with significant morbidity and mortality1-4 for which mild therapeutic hypothermia (TH) is a recommended therapy5-8.

RI PT

Given their young age, increased susceptibility to sudden cardiac death and the potential for therapeutic interventions following recovery, TH is an attractive treatment modality in adult patients with congenital heart disease (ACHD) who suffer cardiac arrest9-10. We

SC

hypothesize that TH can be used to improve survival and reduce neurologic injury in patients with ACHD post-arrest. In this retrospective study, we report a series of 5

M AN U

patients with complex ACHD who presented with sudden cardiac death and were treated with TH. The aim of this study is to report our institutional experience with the implementation, safety and efficacy of TH in this unique patient population.

TE D

Methods:

The study population included 245 consecutive comatose patients following sudden cardiac death who were treated with TH at Vanderbilt University Medical Center

EP

from 2007 to 2013. Patients determined by their treating physician to be suitable for TH were externally cooled to maintain a target body temperature of 32-34 degrees Celsius for

AC C

24 hours following return of spontaneous circulation (ROSC), after which they were passively rewarmed at a rate of 0.25 degrees Celsius per hour. After approval from the institutional review board, data were collected retrospectively including past medical history, initial rhythm, time to ROSC, receipt of bystander cardiopulmonary resuscitation (CPR), length of intensive care unit (ICU) and hospital stay, complications and Cerebral Performance Category (CPC) score at hospital discharge and follow up. Patients were

3

ACCEPTED MANUSCRIPT

considered for inclusion in this study if they had a history of moderate or complex congenital heart disease, suffered a primary cardiac arrest and underwent mild TH postresuscitation.

RI PT

The primary outcome for this study was CPC at hospital discharge. The Cerebral Performance Category score was developed as a measure of central nervous system

function after cardiac arrest and is the most commonly used post-resuscitation outcome

SC

measure for this purpose11. A CPC score of 1 indicates normal neurologic function, CPC 2-4 indicate progressive degrees of neurologic injury and a CPC score of 5 indicates

M AN U

death. We defined a CPC score of 1-2 as a good neurologic outcome.

Results:

Baseline patient characteristics, hospital course and outcomes are displayed in

TE D

Table 1. All patients suffered cardiac arrest due to ventricular arrhythmia and successfully completed treatment with mild hypothermia. Ventricular arrhythmia was the initial rhythm in each ACHD patient compared to 132/245 (54%) of the remaining

EP

cohort. All ACHD patients survived to hospital discharge with good neurologic function (CPC score 1 or 2) and to a mean of 14-month follow up. Furthermore, each adult

AC C

congenital patient underwent an intervention to address the potential underlying etiology of sudden cardiac death including: ligation of ALCAPA; percutaneous coronary intervention; and defibrillator implantation (4/5 patients). In the post-discharge follow up period, 1 patient underwent successful heart-lung transplantation while another received biventricular mechanical support as a bridge-to-transplant. The 2 remaining patients are currently awaiting listing for heart transplantation.

4

ACCEPTED MANUSCRIPT

Discussion: We present our institutional experience with the use of mild TH in 5 patients with

RI PT

various forms of congenital heart disease who suffered a cardiac arrest. Our data shows that the primary mechanism of arrest in each case was ventricular arrhythmia in the

setting of impaired systemic ventricular function. No patient had prior documented or

SC

clinical arrhythmia. While each patient’s length of hospitalization varied (range 7-37 days), the length of ICU stay was relatively short with a mean duration of 4 days.

M AN U

Although 2 of the 5 congenital patients developed infection post-hypothermia, all 5 patients survived to hospital discharge. The mean follow up was 14 months, with exception of patient #5 who resumed her usual outpatient care at another facility. Neurologic recovery was good as evidenced by a mean CPC score of 1 at both discharge

TE D

and outpatient follow up (excluding patient #5 as above). There were no reports of significant functional debility post-arrest.

We acknowledge that this study is limited by a small cohort of patients, which

EP

primarily reflects the low incidence of these conditions within the larger population. In addition, each congenital heart condition represents a unique anatomic, physiologic and

AC C

pathologic entity that may behave differently. Therefore, broad generalization regarding the applicability and effectiveness of mild TH to such a heterogeneous patient population is challenging to make at the present time. In addition, all 5 patients presented as a witnessed arrest and received immediate bystander CPR. None of the 5 suffered asystole or pulseless electrical activity and all were very young. These factors may have

5

ACCEPTED MANUSCRIPT

contributed to the favorable results observed and thus, we cannot extrapolate superior outcomes on the basis of ACHD alone. However, ACHD patients represent a relatively young subset of the population9

RI PT

with identifiable risk for sudden cardiac death10 and therefore, potential for intervention and future prevention. As the proportion of patients with ACHD in the general

population grows9, we hypothesize that the incidence of late complications of their

SC

congenital disease, including sudden cardiac death, will rise in parallel. Therefore, we emphasize the importance of post-resuscitation care in these particularly high-risk

M AN U

patients and note that by improving post-arrest neurologic outcome, we can potentially allow for further risk stratification (eg, ICD placement, anti-arrhythmic drug therapy) and long-term management (eg, mechanical circulatory support, heart or combined heart-lung transplantation).

TE D

We also highlight the need for multi-disciplinary care for these patients undergoing TH or other therapies while in the intensive care unit. As each patient in this case series offers a unique congenital abnormality and scenario demanding tailored

EP

treatment considerations, this underscores the importance of integrating care along a team-based approach that involves specialists in critical care, congenital heart disease,

AC C

heart failure and transplant, interventional cardiology and electrophysiology. Within large tertiary care centers where complex congenital patients may be referred and where advanced diagnostic and treatment modalities such as TH are available, the need for cardiologists with advanced training in understanding the anatomic and physiologic complexities of ACHD is vital. Furthermore, present management guidelines in adult

6

ACCEPTED MANUSCRIPT

congenital heart disease do not specifically comment on either post-cardiac arrest care or

AC C

EP

TE D

M AN U

SC

RI PT

therapeutic hypothermia for this high-risk population12-14.

7

ACCEPTED MANUSCRIPT

1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM,

RI PT

Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics Committee and Stroke

SC

Statistics Subcommittee. Executive Summary: Heart Disease and Stroke Statistics-2012

M AN U

Update: A Report From the American Heart Association. Circulation 2012;125:188–197. 2. Kern KB. Optimal Treatment of Patients Surviving Out-of-Hospital Cardiac Arrest. JACC Cardiovasc Interv 2012;5:597–605.

3. Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Böttiger BW, Callaway C, Clark

TE D

RS, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT, Merchant RM, Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Hoek TV. Post-cardiac arrest syndrome:

EP

Epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart

AC C

Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation 2008;79:350–379.

4. Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Böttiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT Jr, Merchant RM,

8

ACCEPTED MANUSCRIPT

Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Vanden Hoek T. Post-Cardiac Arrest Syndrome: Epidemiology, Pathophysiology, Treatment, and Prognostication A Consensus Statement

RI PT

From the International Liaison Committee on Resuscitation (American Heart

Association, Australian and New Zealand Council on Resuscitation, European

Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart

SC

Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern

Africa); the American Heart Association Emergency Cardiovascular Care Committee; the

M AN U

Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008;118:2452–2483.

5. Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to

TE D

Improve the Neurologic Outcome after Cardiac Arrest. N Engl J Med 2002;346:549–556. 6. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K.

EP

Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced

AC C

Hypothermia. N Engl J Med 2002;346:557–563. 7. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL. Part 9: Post-Cardiac Arrest Care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S768–786. 8. Nolan JP, Morley PT, Hoek TL, Hickey RW, Advancement Life Support Task Force

9

ACCEPTED MANUSCRIPT

of the International Liaison committee on Resuscitation. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advancement Life Support Task Force of the

RI PT

International Liaison Committee on Resuscitation. Resuscitation 2003;57:231–235. 9. Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital Heart Disease in the General Population: Changing Prevalence and Age Distribution. Circulation

SC

2007;115:163–172.

10. Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of Death in

M AN U

Adults With Congenital Heart Disease. Am J Cardiol 2000;86:1111–1116. 11. Becker LB, Aufderheide TP, Geocadin RG, Callaway CW, Lazar RM, Donnino MW, Nadkarni VM, Abella BS, Adrie C, Berg RA, Merchant RM, O'Connor RE, Meltzer DO, Holm MB, Longstreth WT, Halperin HR; American Heart Association

TE D

Emergency Cardiovascular Care Committee; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Primary Outcomes for Resuscitation Science Studies: A

2177.

EP

Consensus Statement From the American Heart Association. Circulation 2011;124:2158–

AC C

12. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, del Nido P, Fasules JW, Graham TP Jr, Hijazi ZM, Hunt SA, King ME, Landzberg MJ, Miner PD, Radford MJ, Walsh EP, Webb GD, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Page RL, Riegel B, Tarkington LG, Yancy CW. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American

10

ACCEPTED MANUSCRIPT

Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society,

RI PT

International Society for Adult Congenital Heart Disease, Society for Cardiovascular

Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol

SC

2008;52:e143-263.

13. Baumgartner H, Bonhoeffer P, De Groot NM, de Haan F, Deanfield JE, Galie N,

M AN U

Gatzoulis MA, Gohlke-Baerwolf C, Kaemmerer H, Kilner P, Meijboom F, Mulder BJ, Oechslin E, Oliver JM, Serraf A, Szatmari A, Thaulow E, Vouhe PR, Walma E; Task Force on the Management of Grown-up Congenital Heart Disease of the European Society of Cardiology (ESC); Association for European Paediatric Cardiology (AEPC); ESC Committee for Practice Guidelines (CPG). ESC Guidelines for the management of

TE D

grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31:2915-2957.

14. Silversides CK, Salehian O, Oechslin E, Schwerzmann M, Vonder Muhll I, Khairy

EP

P, Horlick E, Landzberg M, Meijboom F, Warnes C, Therrian J. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart

AC C

disease: Complex congenital cardiac lesions. Can J Cardiol 2010;26:e98-117.

11

Table 1 Baseline characteristics and outcomes of the 5 patients Variable #1 Age (years) at arrest 20 Sex Female ALCAPA

#2 23 Male

Patient #3 27 Male

L-TGA

D-TGA

VF 20 In hospital N/A 20

#5 38 Female ASD, subaortic membrane, cleft MV VF 20 Out of hospital Yes 35

56

180

95

Pneumonia 5 1 37 1 14 1

Pneumonia, AF 4 1 15 1 15 1

0 4 2 11 1 X X

AC C

EP

TE D

M AN U

Initial rhythm VF VT 15 Time to ROSC (minutes) 11 Out of hospital Location of arrest Out of hospital Yes Bystander CPR Yes 52 Time to initiation of TH (minutes) 60 Time to reach target temperature 266 120 (minutes) Complications during hospitalization 0 0 4 Length of ICU stay (days) 2 2 CPC at ICU discharge 1 10 Length of hospitalization (days) 7 1 CPC at hospital discharge 2 11 Follow up interval (months) 17 1 CPC at follow up 1 AF = atrial fibrillation ALCAPA = anomalous left coronary artery from the pulmonary artery ASD = atrial septal defect CPC = cerebral performance category CPR = cardiopulmonary resuscitation D-TGA = dextro-transposition of the great arteries ICU = intensive care unit L-TGA = levo-transposition of the great arteries MV = mitral valve ROSC = return of spontaneous circulation TH = therapeutic hypothermia VF = ventricular fibrillation VSD = ventricular septal defect VT = ventricular tachycardia X = patient #5 resumes follow up with another facility

#4 34 Male ASD, tricuspid atresia, VSD VT 10 Out of hospital Yes 32

SC

Type of congenital disease

RI PT

ACCEPTED MANUSCRIPT