The Cardiomyopathy of Sickle Cell Disease

Cardiac morbidity, early mortality, and sudden death are the major consequences of sickle cell disease (SCD) in patients surviving into adulthood. Pulmonary hypertension (PH), elevated tricuspid regurgitant jet velocity (TRV), and diastolic dysfunction have all been identified to correlate with early mortality in adults with SCD. However, the unifying pathophysiology behind these abnormalities and its connection with early mortality and sudden death have not been recognized previously. We have found that SCD patients have a unique cardiomyopathy characterized by restrictive physiology (diastolic dysfunction, left atrial dilation and normal systolic function) superimposed on features of hyperdynamic circulation (left ventricular [LV] enlargement and eccentric LV hypertrophy. The restrictive cardiomyopathy of SCD causes pulmonary congestion and post-capillary PH. This can be detected by a mild elevation in TRV, which is likely a marker of the SCD-related cardiomyopathy rather than pulmonary arterial disease. Similar to other restrictive cardiomyopathies, the SCD cardiomyopathy predisposes to arrhythmias and sudden death, even when pulmonary pressures are not severely elevated. We have also found that diffuse myocardial fibrosis is common in SCD and may underlie the diastolic dysfunction, but more studies are needed to understand the mechanisms of SCD-related cardiomyopathy and to identify new therapies to decrease cardiac morbidity and improve the life expectancy of SCD patients.