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Five-minute heart rate variability can predict obstructive angiographic coronary disease
  1. D Kotecha1,2,
  2. G New3,
  3. M D Flather2,
  4. D Eccleston1,
  5. J Pepper4,
  6. H Krum1
  1. 1Monash Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia
  2. 2Clinical Trials and Evaluation Unit, Royal Brompton Hospital and Imperial College, London, UK
  3. 3Box Hill Hospital, Monash University, Melbourne, Australia
  4. 4Department of Cardiothoracic Surgery, Royal Brompton Hospital and Imperial College, London, UK
  1. Correspondence to Dr Dipak Kotecha, Clinical Trials and Evaluation Unit, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; dipak.kotecha{at}


Objective Obstructive coronary artery disease (CAD) is evident in only half of patients referred for diagnostic angiography. Five-minute heart rate variability (HRV) is a non-invasive marker for autonomic control of the vasculature, which this study hypothesised could risk-stratify cardiac patients and reduce unnecessary angiograms.

Design A prospective observational study (the Alternative Risk Markers in Coronary Artery Disease (ARM–CAD) study).

Setting Three cardiac centres in Melbourne, Australia.

Patients 470 consecutive patients undergoing elective angiography (with predominantly normal cardiac rhythm), regardless of co-morbidity.

Main outcome measures The presence of obstructive CAD (≥50% stenosis) on angiography.

Results Patients with obstructive CAD had significantly reduced HRV, particularly in the low frequency (LF) range (median 180 vs 267 ms2 without CAD; p<0.001). There was a linear trend with the severity of CAD; median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400), single-vessel CAD 212 (396) and more severe disease 170 (327) ms2; p value for trend 0.003. There was a similar reduction in LF power regardless of the anatomical location of coronary stenoses. Comparing patients with LF less than 250 and 250 ms2 or greater, the adjusted OR for obstructive CAD using multivariate regression was 2.42, 95% CI 1.33 to 4.38 (p=0.004). No interactions were noted in subgroup analysis and HRV added to risk prediction irrespective of the baseline Framingham risk (p<0.0001).

Conclusion Low HRV is strongly predictive of angiographic coronary disease regardless of other co-morbidities and is clinically useful as a risk predictor in patients with sinus rhythm.

Clinical trial registration information

  • Aortic root disease
  • aortic valve disease
  • coronary angiography
  • coronary artery disease
  • coronary bypass surgery
  • dissection
  • heart rate variability
  • Marfans
  • risk factors
  • risk stratification
  • statistics

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  • Funding The ARM-CAD study was investigator initiated and supported by the Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, the Royal Brompton and Harefield NHS Trust Clinical Trials and Evaluation Unit, London, and an unrestricted research grant from IM Medical Ltd, Melbourne.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was approved by Monash University, Alfred Hospital HREC, Eastern Health HREC, Northern Hospital HREC.

  • Provenance and peer review Not commissioned; externally peer reviewed.