Myocardial perfusion defects in Bartter and Gitelman syndromes

Abstract

Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events. Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two-dimensional and myocardial contrast echocardiography. BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 +/- 9.1 ms (P < 0.001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 +/- 4% to 78 +/- 5%, P < 0.003) while in seven BS/GS patients (Group 1) it declined (64 +/- 5% to 43 +/- 9%, P < 0.001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: beta (a measure of myocardial flow velocity; 0.89 +/- 0.12 vs. 0.99 +/- 0.12, P < 0.001) and myocardial blood volume (14.4 +/- 2 vs. 20.2 +/- 0.25, P < 0.001), while in Group 1 BS/GS it decreased (0.87 +/- 0.15 vs. 0.67 +/- 0.15, P < 0.001; and 14.5 +/- 1.9 vs. 8.3 +/- 0.22, P < 0.001, respectively). Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in-depth cardiac assessment in order to identify patients at higher risk.