Sudden unexpected death in heart failure may be preceded by short term, intraindividual increases in inflammation and in autonomic dysfunction: a pilot study

Objective: To see whether sudden unexpected death in chronic heart failure is preceded by intraindividual
worsening in inflammation and in ECG criteria.
Design and setting: Prospective cohort study conducted in the community.
Patients: 34 patients with chronic heart failure were studied. Their mean (SD) age was 68 (8) years, 29
were men, mean (SD) left ventricular ejection fraction was 29 (9)%, and they were in New York Heart
Association functional class II (n = 20), III (n = 11), and IV (n = 3). The patients were examined monthly
over 24 months, with sequential measurement of C reactive protein and neutrophil counts and 24 hour
ambulatory ECG monitoring measuring heart rate variability, mean heart rate, and arrhythmias.
Intraindividual changes in these parameters were related to subsequent cardiac deaths.
Results: During follow up, nine patients died: five patients had a sudden unexpected death (SUD) and four
died of progressive heart failure (PHF). There were significant intraindividual changes in neutrophil counts
(p = 0.02), C reactive protein (p = 0.039), and heart rate variability (p ( 0.018) in those who died of
SUD and PHF. In contrast no significant changes were seen in ventricular extrasystoles, ventricular
tachycardia episodes, brain natriuretic peptide, or aldosterone in the SUD group, but all of these
parameters did increase as expected in those who died of PHF.
Conclusions: This is preliminary evidence that SUD may be preceded by intraindividual increases in both
inflammation and autonomic dysfunction. Both may be causal in genesis but, even if they are not,
intraindividual increases in either may be convenient markers to identify patients at high risk of impending
SUD. Larger studies are needed to confirm the observation from this pilot study.