Elsevier

Resuscitation

Volume 166, September 2021, Pages 74-82
Resuscitation

Clinical paper
Repolarization and ventricular arrhythmia during targeted temperature management post cardiac arrest

https://doi.org/10.1016/j.resuscitation.2021.07.004Get rights and content

Abstract

Background

Targeted temperature management (TTM) following out-of-hospital cardiac arrest (OHCA) prolongs the QT-interval but our knowledge of different temperatures and risk of arrhythmia is incomplete.

Objective

To assess whether the QTc, QT-peak (QTp) and T-peak to T-end interval (TpTe) may be useful markers of ventricular arrhythmia in contemporary post cardiac arrest treatment.

Methods

An ECG-substudy of the TTM-trial (TTM at 33 °C vs. 36 °C) with serial ECGs from 680 (94%) patients. Bazett’s (B) and Fridericia’s (F) formula were used for heart rate correction of the QT, QTp and TpTe. Ventricular arrhythmia (VT/VF) were registered during the first three days of post cardiac arrest care.

Results

The QT, QTc and QTp intervals were prolonged more at 33 °C compared to 36 °C and restored to similar and lower levels after rewarming. The TpTe-interval remained between 92–100 ms throughout TTM in both groups.

The QTc intervals were associated with ventricular arrhythmia, but not after adjustment for cardiac arrest characteristics. The QTp-interval was not associated with risk of ventricular arrhythmia. Heart rate corrected TpTe-intervals were associated with higher risk of arrhythmia (Odds ratio (OR): TpTe(B): 1.12 (1.02–1.23, p = 0.01 TpTe(F): 1.12 (1.02–1.23, p = 0.02) per 20 ms). Further a prolonged TpTe-interval ≥ 90 ms was consistently associated with higher risk (ORadjusted: TpTe(B): 2.05 (1.25–3.37), p < 0.01, TpTe(F): 2.14 (1.32–3.49), p < 0.01).

Conclusions

TTM prolongs the QT-interval by prolongation of the QTp-interval without association to increased risk. The TpTe-interval is not significantly affected by core temperature, but heart rate corrected TpTe intervals are robustly associated with risk of ventricular arrhythmia.

Trial registration

The TTM-trial is registered and accessible at ClinicalTrials.gov (Identifier: NCT01020916).

Introduction

The chance of survival after Out-of-hospital cardiac arrest (OHCA) has increased in recent years1 but is greatly affected by the chain of survival with early recognition and initiation of basic and advanced life support with early defibrillation.2., 3. The last link in the chain of survival includes post resuscitation care, aiming to treat the precipitating cause, ameliorate the effects of the post cardiac arrest syndrome and restoring quality of life.4

Targeted temperature management (TTM)5., 6. is currently the only guideline supported modality for reduction of anoxic brain injury. While TTM has been widely implemented,7 complications including impaired coagulation, infections and arrhythmia are frequent, affecting >50% of patients5., 6., 8. with cardiac arrhythmia being the most frequent.9., 10. Lowering of the core temperature affects many organ systems, and hypothermia can increase risk of ventricular arrhythmia.11

Prolongation of the QT-interval during TTM has gained increasing focus in recent years12., 13. with unclear relation to arrhythmia. Different parts of the QT-interval may be affected by TTM and with differential impact on risk of arrhythmia. Late repolarization, defined as the T-peak to T-end interval (TpTe) has been associated with increased risk of arrhythmia in Brugada syndrome,14 hypertrophic cardiomyopathy15 sudden cardiac death16 and other cardiac diseases.17

The present study aims to quantify the differential effects of two levels of TTM (33 °C vs. 36 °C) on the QT-interval and the initial and late cardiac repolarization in a large cohort of comatose OHCA patients and to assess the association between prolonged repolarization and the risk of life-threatening ventricular arrhythmia during post cardiac arrest care.

Section snippets

Study design and population

The current study is a pre-defined ECG sub-study of the TTM-trial,8 previously described.18 The main study was an investigator initiated, international randomized clinical trial including adult comatose OHCA patients (n = 939). Patients were enrolled from November 2010 to January 2013 in a 1:1 fashion to TTM targeting either 33 °C or 36 °C, with similar outcomes between the groups.8 Twenty-four of 36 TTM-sites participated in the ECG-substudy, leaving 682 patients (94%) with available ECGs post

Baseline characteristics

Included patients were well balanced for the randomization between TTM at 33 °C vs. 36 °C (Table 1). Patients were middle-aged, predominantly men and with similar degree of comorbidity. The majority had witnessed OHCA and with bystander CPR being performed and no significant differences in pre-hospital cardiac arrest characteristics. In terms of in-hospital assessment and treatment, no significant differences were found (Table 1). No significant difference in arrhythmia or pre-existing

Discussion

We found that the QT-interval increases more during TTM at 33 °C compared to 36 °C, supporting the notion that the QT-interval increases by lower core temperatures. A significant interaction over time was present after heart rate correction with Fridericiás formula, but not with Bazett́s formula though a significant difference was present at TT. The prolongation of the QT-interval was primarily observed in the initial repolarization by higher QTp at TTM at 33 °C. Both the total QT-interval and

Strengths and limitations

The present study represents prospective enrolment of comatose OHCA-patients in a multinational randomized controlled design. The database consists of serial ECGs during TTM at two levels, and this is to our knowledge the largest clinical ECG-database of its kind. We believe that data yields high external validity, as it represents data from the currently guideline supported levels of TTM used worldwide. While the vast majority of patients (94%) eligible for the substudy had recorded ECGs,

Conclusion

TTM prolongs the QT-interval by prolongation of the QT-peak without association to increased risk of ventricular arrhythmia. The TpTe-interval is not significantly affected by core temperature, but heart rate corrected TpTe-intervals are robustly associated with increased risk of ventricular arrhythmia. The unaffected late repolarization (TpTe) with a threshold ≥ 90 ms may be a more reliable marker for risk assessment than conventional QT measurement in post cardiac arrest care during TTM in

Funding sources

The Danish Heart Foundation (Grant no: 13-04-R94-A4460-22756 and 14-R97-A5142-22831) has supported this study with 18 months of salary in JHT́s Ph.D. project. The TTM-trial was funded by independent research grants from non-profit or governmental agencies: Swedish Heart Lung Foundation; Arbetsmarknadens försäkringsaktiebolag (AFA)-insurance Foundation; The Swedish Research Council; Regional research support, Region Skåne; Governmental funding of clinical research within the Swedish NHS

Declaration of Competing Interest

All authors have completed the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. LK, JK, SP and CH report personal fees from Honorarium for speeches given at symposia, outside the submitted work. Otherwise none declared. This study has been conducted without any relationship with industry.

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