Oral Presentation 6th Australian Health and Medical Research Congress 2012

Translational Research and the Coronary Slow Flow Phenomenon (#196)

John Beltrame 1
  1. University of Adelaide, Adelaide, SA, Australia

The coronary slow flow phenomenon (CSFP) was considered an angiographic curiosity 20 years ago but has now evolved to a recognised clinical disorder with some investigators referring to it as ‘Syndrome Y’. Angiographically, the condition is characterised as delayed filling of the distal coronary vasculature despite the absence of significant obstructive coronary artery disease. Previously this was thought to be ‘interesting’ but the patient was instructed that their chest pain was not cardiac in nature and that no further follow-up was necessary. However, systematic clinical studies confirmed that an increased coronary microvascular resistance was responsible for the delayed vessel filling and that the CSFP was a new coronary microvascular disorder. Moreover, during the clinical management of these patients, it became apparent that the novel calcium channel blocker, mibefradil, was particularly effective in controlling the chest pain experienced by these patients. These clinical observations were confirmed in a randomised, double-blind, placebo-controlled, cross-over study that documented a 56% reduction in angina frequency with prolonged episodes reduced by over 70%.

In a bedside-to-bench approach, basic laboratory techniques were employed to elucidate the mechanisms responsible for the increased coronary microvascular resistance and the benefits of mibefradil. These isolated microvessel physiologic and molecular studies implicated the potent microvascular constrictor endothelin as a potential pathogenetic agent with the calcium T-channel also involved. These findings have provided further therapeutic targets for clinical studies.

Clinical epidemiologic approaches have also been utilised to increase our understanding of this disorder.  On-going studies are evaluating the clinical outcomes experienced by these patients, with the intention of identifying predictive clinical markers. Also, genetic polymorphism studies have contributed to our understanding of the disorder.

In summary, the CSFP exemplifies how translational research utilising basic, clinical and epidemiologic methods can result in the discovery of a novel disorder, an understanding of its mechanisms and identification of an effective therapy, thereby improving patient care.