CARDIOVASCULAR MEDICINE

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

A M A Shehab¹, R J MacFadyen¹, M McLaren², R Tavendale², J J F Belch², A D Struthers¹

¹ Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK
² Department of Medicine, Ninewells Hospital and Medical School

Correspondence to:
Correspondence to:
Professor Allan D Struthers
Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK; a.d.struthers{at}dundee.ac.uk

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.

Abbreviations: BNP, brain natriuretic peptide; CHF, chronic heart failure; ELISA, enzyme linked immunosorbent assay; IMPRESS, mmunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; PHF, progressive heart failure; SDNN, standard deviation of all NN intervals; SUD, sudden unexpected death; TI, triangular index; UK-HEART, UK heart failure evaluation and assessment of risk trial

Keywords: chronic heart failure; heart rate variability; C reactive protein; sudden cardiac death

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