Gerry Coghlan, MD, FRCP, studied cardiology at Harefield Hospital from 1988 to 1994, where he also completed his MD thesis (in association with Brunel University) on “Free Radicals in Ischaemic Heart Disease”. He became Consultant Interventional Cardiologist at the Royal Free Hospital in 1997, where he has developed, together with Professor Dame Carol Black & Prof C Denton, a specialist pulmonary hypertension service for patients with connective tissue disease. Dr. Coghlan is a founder member of the Pulmonary Hypertension Physicians’ Group, which has standardised care for pulmonary arterial hypertension (PAH) in the UK, and has worked with government organisations (NSCAG) to secure funding for PAH as a recognised supraregional speciality.
Abstract: Heart and pulmonary vasculature in sickle cell disease
Impaired effort tolerance and early cardiovascular mortality are well documented in sickle cell disease, nevertheless real difficulty has been encountered in providing clear methods of diagnosing or treating the suggested underlying abnormalities.
Abnormalities of nitric oxide metabolism leading to a high prevalence of proliferative pulmonary arteriopathy was assumed to be an important contributor when Gladwin et al found a strong association between tricuspid velocity and outcome. The result was two unsuccessful large-scale therapeutic trials. A number of investigators have recently fully characterised the population with elevated TV invasively, showing that most of these patients do not have pulmonary arterial hypertension or post capillary pulmonary hypertension. Patients with isolated TV abnormalities do not exhibit a worse functional capacity when compared to those with a normal TV. By contrast studies relying on echocardiographic evaluation alone demonstrate a clear relationship between TV and effort intolerance.
The failure to find a high prevalence of pulmonary arterial hypertension in patients with raised TV has led to consideration of diastolic dysfunction as a cause of raised pulmonary pressures, thus in parallel much effort has been directed toward understanding the basis of this assumed cardiac abnormality. Evidence has been presented supporting endothelial dysfunction leading to reduced systemic arterial compliance, cardiac autonomic dysfunction and electrophysiological abnormalities. In addition a high prevalence of more subtle markers of diastolic dysfunction have been identified. Thus the concept of minor cardiac abnormalities leading to exercise limitation and cardiac mortality remains unfalsified.
The question at present is whether TV associated morbidity and mortality reflect a very poor outcome and in the subgroup with cardiac and pulmonary vascular abnormalities, are explained by non cardiac issues such as chronic haemolysis or are artifactual. Only large scale prospective studies of markers of morbidity and mortality in well characterized populations will ultimately provide much needed clarity.