Author + information
- aDepartments of Cardiovascular Diseases, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota
- bDepartment of Internal Medicine (Internal Medicine Residency and Clinician-Investigator Training Programs), Mayo Clinic, Rochester, Minnesota
- ↵∗Reprint requests and correspondence:
Dr. Michael J. Ackerman, Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory, Guggenheim 501, Mayo Clinic, 200 First Street, SW, Rochester, Minnesota 55905.
Cardiac implantable electronic device (CIED) is an umbrella term that describes pacemakers, implantable-defibrillators (ICDs), and cardiac resynchronization devices useful in the treatment of and or prevention of sudden cardiac death (SCD) secondary to an array of cardiac arrhythmias and conduction disorders. Although randomized clinical trials have shown clearly that CIEDs confer a survival benefit in patients at high risk for life-threatening arrhythmias (1–4), according to clinical criteria, ∼3% to 16% of patients with CIEDs still have a sudden arrhythmia-related death (1,3,5). In these patients, post-mortem CIED interrogation has proved helpful in further defining the cause or causes of death and ruling out CIED malfunction (5–8). As a result, the American College of Cardiology/American Heart Association–endorsed Heart Rhythm Society CIED performance guidelines encourage the use of post-mortem CIED interrogation in SCD (9). Furthermore, amid concerns regarding the adequacy of current CIED post-marketing surveillance (10), post-mortem CIED interrogation represents one of many approaches that could lead to quicker detection and resolution of potential CIED-related safety issues. However, post-mortem CIED interrogations are seldom performed in clinical practice (11), possibly because of a paucity of evidence available to define the clinical settings (i.e., in-hospital vs. out-of-hospital death) and indications (i.e., nonselective vs. SCD-only) in which post-mortem CIED interrogation use would be most beneficial.
In this issue of the Journal, Sinha et al. (12) analyze the utility of nonselective post-mortem CIED interrogation in a registry of 84 predominantly in-hospital decedents with CIEDs undergoing complete or partial autopsy with the hope of better defining the role CIED interrogation in non-SCD cases. When viewed in the context of a recent, but starkly contrasted, prospective study by Tseng et al. (8) that used post-mortem CIED interrogation to further elucidate the cause of death in 22 out-of-hospital SCD victims, the large post-mortem CIED autopsy study by Sinha et al. (12) provides an ample foundation from which to begin the process of determining what clinical settings or indications, if any, warrant consistent use of post-mortem CIED interrogation.
To this end, Sinha et al. (12) advocate for the use of post-mortem CIED interrogation to define the cause and timing of death more accurately in all decedents undergoing autopsy investigation. This recommendation is made largely on the basis of the intriguing finding that 19.5% (9 of 41) of decedents in their non-SCD cohort had clinically significant CIED alerts defined as any tachyarrhythmia within 24 hours of death or an elevated intrathoracic impedance suggesting impending cardiorespiratory compromise in the weeks before death (12). As noted by the investigators, most of the CIED alerts in the non-SCD death cohort were the result of elevated intrathoracic impedance (7 of 9; 77.8%) rather than tachyarrhythmia (2 of 9; 22.2%) (12). Furthermore, the 2 tachyarrhythmia CIED alerts represented situations in which ventricular tachycardia or ventricular fibrillation (VT/VF) was appropriately sensed, and an internal VT/VF-terminating shock was delivered (12).
Although elevated intrathoracic impedance is a relatively sensitive and specific finding in congestive heart failure, it is difficult to imagine many clinical situations resulting in unexpected death in which an elevated post-mortem intrathoracic impedance measurement would lead to the discovery of pulmonary edema and/or other significant cardiorespiratory disease (e.g., pneumonia, pleural effusion, acute respiratory distress syndrome, etc.) that would have gone otherwise undetected during the clinical work-up and ensuing autopsy. As such, it is difficult to argue for the routine use of nonselective post-mortem CIED interrogation at this juncture. However, this analysis should not dissuade future investigators from using nonselective approaches because larger, multi-institution studies may yield more compelling findings and are needed to define the role of CIED interrogation completely in the post-mortem investigation of non-SCD.
Perhaps the more intriguing and potentially clinically important finding reported by Sinha et al. (12) does not pertain to CIED alerts in non-SCD, but rather relates to those instances in the SCD cohort when ICD programming or performance (7 of 43; 16.3%) was called into question by the reviewing electrophysiologists. A similar trend was also noted by Tseng et al. (8), who observed a high number of CIED concerns in their out-of-hospital SCD analysis (10 of 22; 45.5%), including both hardware failures (4 of 22; 18.2%) and ICD programing or performance issues (6 of 22; 27.3%) (8). Potential VT/VF undersensing was by far the most commonly encountered CIED performance concern in both in-hospital (4 of 7; 57.1%) (12) and out-of-hospital (5 of 10; 50%) SCD (8). This finding illuminates the need to investigate further the possibility that delayed-style ICD programming, previously shown to decrease the rate of inappropriate shocks and improve short-term outcomes for patients (13), may unintentionally increase the long-term risk of SCD.
It is not clear whether the decreased rate of CIED concerns, specifically the absence of hardware failure, between the studies of Sinha et al. (12) and Tseng et al. (8) reflect: 1) a focus on in-hospital versus out-of-hospital SCD; 2) the inclusion versus exclusion of non-SCD; 3) differences in study design or clinical interpretation of CIED events; 4) regional practice or population differences; or 5) a combination of these and other factors. However, these two recent studies provide compelling collective evidence for the more widespread use of post-mortem CIED interrogation in SCD. Not only does post-mortem CIED interrogation afford an opportunity to define the cause and timing of suspected SCDs more clearly, but as evidenced by the issue of VT/VF undersensing, it also has the potential to add a silver lining to otherwise tragic deaths by providing a mechanism to identify CIED hardware failures or performance issues more quickly, with the goal of further optimizing potentially life-saving CIED therapies for future recipients.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the author and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Ackerman is a consultant for Boston Scientific, Gilead Sciences, Invitae, Medtronic, and St. Jude Medical; and from 2004 through 2015, Dr. Ackerman and Mayo Clinic received sales-based royalties from Transgenomic for their FAMILION-LQTS and FAMILION-CPVT genetic tests; however, none of these entities participated in this study. Dr. Giudicessi has reported that he has no relationships relevant to the contents of this paper to disclose.
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