Imaging of myocardial cell apoptosis uncovers early signs of worsening heart failure

A SPECT imaging protocol that detects programmed cell death with technetium-99m annexin A5 may give clinicians an early warning of worsening heart failure.

Myocardial apoptosis imaged with annexin A5 enabled researchers in the cardiology and nuclear medicine departments at the University of Maastricht in the Netherlands to differentiate patients whose conditions would improve from patients who would decline in the year after imaging.

Dr. Bas L.J.H. Kietselaer and colleagues in the laboratory of Dr. Leo Hofstra tested the annexin A5 protocol on nine consecutive patients with nonischemic cardiomyopathy and advanced heart failure. Eight had idiopathic dilated cardiomyopathy. The remaining patient had developed heart failure secondary to familial hypertropic cardiomyopathy caused by a mutation in the myosin gene at locus 14q11-q12.

Coronary angiography was performed to exclude patients with coronary artery disease, and ventricular function was quantified.

Imaging was performed on a dual-head gamma camera six hours after intravenous administration of Tc-99m annexin A5 and 30 minutes after an injection of thallium-201 for myocardial perfusion.

The trial's results suggest success beyond meeting the modest goal of establishing the feasibility of Tc-99m annexin A5 SPECT with a small group of patients. Of the nine congestive heart failure patients in the trial, four showed annexin A5 uptake indicative of regions of elevated apoptosis in the left ventricular myocardium. No uptake was seen in the right ventricles of these patients.

Uptake was focal in one patient, multifocal in two patients, and diffuse in one patient. It did not correspond with single coronary territories, however, as often seen after myocardial infarction, according to the authors.

The potential prognostic value of these results became clear when the ventricular function was measured again a year later. Left ventricular ejection fraction had fallen an average of 10% for the four patients who had positive annexin A5 uptake in their initial scans. The left ventricular ejection fractions of all five patients without initial annexin A5 uptake either rose or remained stable. The average increase was 7%.

The ability of annexin A5 to detect programmed cell death in this way is especially relevant in light of the development of caspase 3 inhibitors to reduce the amount of myocardial damage inflicted by various diseases, according to Kietselaer. Though conclusions must be tempered by small sample size, its results suggest that Tc-99m annexin A5 could be used to monitor the direct cellular effects of anti-apoptotic treatments.

Results were reported in the April issue of the Journal of Nuclear Medicine (2007;48[4]:562-567).

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