Sudden Cardiac Death and Myocardial Fibrosis, Determined by Autopsy, in Persons with HIV

Abstract

Background: The incidence of sudden cardiac death and sudden death caused by arrhythmia, as determined by autopsy, in persons with human immunodeficiency virus (HIV) infection has not been clearly established.

Methods: Between February 1, 2011, and September 16, 2016, we prospectively identified all new deaths due to out-of-hospital cardiac arrest among persons 18 to 90 years of age, with or without known HIV infection, for comprehensive autopsy and toxicologic and histologic testing. We compared the rates of sudden cardiac death and sudden death caused by arrhythmia between groups.

Results: Of 109 deaths from out-of-hospital cardiac arrest among 610 unexpected deaths in HIV-positive persons, 48 met World Health Organization criteria for presumed sudden cardiac death; of those, fewer than half (22) had an arrhythmic cause. A total of 505 presumed sudden cardiac deaths occurred between February 1, 2011, and March 1, 2014, in persons without known HIV infection. Observed incidence rates of presumed sudden cardiac death were 53.3 deaths per 100,000 person-years among persons with known HIV infection and 23.7 deaths per 100,000 person-years among persons without known HIV infection (incidence rate ratio, 2.25; 95% confidence interval [CI], 1.37 to 3.70). Observed incidence rates of sudden death caused by arrhythmia were 25.0 and 13.3 deaths per 100,000 person-years, respectively (incidence rate ratio, 1.87; 95% CI, 0.93 to 3.78). Among all presumed sudden cardiac deaths, death due to occult drug overdose was more common in persons with known HIV infection than in persons without known HIV infection (34% vs. 13%). Persons who were HIV-positive had higher histologic levels of interstitial myocardial fibrosis than persons without known HIV infection.

Conclusions: In this postmortem study, the rates of presumed sudden cardiac death and myocardial fibrosis were higher among HIV-positive persons than among those without known HIV infection. One third of apparent sudden cardiac deaths in HIV-positive persons were due to occult drug overdose. (Supported by the National Heart, Lung, and Blood Institute.).

Figure 1.. Identification of HIV-Positive Persons with Presumed Sudden Cardiac Death.

Cases of presumed sudden cardiac death (SCD) among persons with known human immunodeficiency virus (HIV) infection were identified through active medical examiner surveillance of all out-of-hospital cardiac arrests among all out-of-hospital deaths in San Francisco County from February 1, 2011, through September 21, 2016. Out-of-hospital cardiac arrest was defined as an event for which the primary impression of emergency medical services (EMS) responders was cardiac arrest. Presumed sudden cardiac death was defined according to World Health Organization (WHO) criteria. Persons who were not symptom-free when last seen alive or who had recently reported symptoms were not considered to meet criteria for presumed sudden cardiac death. DNR denotes do not resuscitate.

Figure 2.. Incidence Rates for HIV-Positive Persons and the Reference Population.

Observed incidence rates per 100,000 person-years are shown for persons with presumed sudden cardiac death and sudden death from arrhythmia, as determined by autopsy, in San Francisco County from February 1, 2011, to September 21, 2016, for HIV-positive persons and from February 1, 2011, to March 1, 2014, for persons in the reference population. The percentages within the bars are the percentages of persons with presumed sudden cardiac death whose deaths were from arrhythmia. Total, sex-specific, and race or ethnic group–specific incidence rate ratios for presumed sudden cardiac death and sudden death from arrhythmia are shown. Confidence intervals for incidence rates and incident rate ratios are 95% confidence intervals, except those for HIV-positive incidence rates for presumed sudden cardiac deaths among Asian and Other populations and confirmed sudden death from arrhythmia among Female, Asian, Hispanic, and Other population groups, which are one-sided 97.5% confidence intervals.

Figure 3.. Quantitative Histologic Analysis of Cardiac Fibrosis.

Shown are trichrome-stained sections of the left ventricle in persons with HIV infection and persons in the reference group (persons without known HIV infection) with sudden death from arrhythmia and sudden death from nonarrhythmic causes. Cases analyzed are those for which consent was obtained from the family of the deceased person. Cases with histologic data as compared with all cases of presumed sudden cardiac death (with respect to demographics, premortem conditions, and final causes of death) are shown in Table S4. For each set of fibrosis data, overall mean (±SD) and percent difference values are shown according to group (HIV-positive group or reference group) and according to cause of presumed sudden cardiac death (arrhythmic or nonarrhythmic), as determined by autopsy. Total fibrosis data include interstitial, perivascular, and replacement fibrosis from the standardized right ventricular free wall; and septal, anterior, inferior, and lateral left ventricular free-wall areas. Samples stained with Masson’s trichrome were assigned fibrosis scores quantified by means of digital image analysis with the use of the Aperio ImageScope (Leica Biosystems) Positive Pixel Count algorithm calibrated for hue and color saturation thresholds of Masson’s trichrome staining. Scores are reported as a percentage of total slide tissue area from all available sections. Differences in fibrosis scores by HIV status were estimated with the use of linear models for log-transformed scores, with adjustment for age, sex, and presence or absence of congestive heart failure, coronary artery disease, and cardiomyopathy. Coefficient estimates were back-transformed to obtain between-group percentage differences.