Barry H. McKeown

Effects of Intravenous Levosimendan on Human Coronary Vasomotor Regulation, Left Ventricular Wall Stress, and Myocardial Oxygen Uptake

Background—Levosimendan is a calcium-sensitizing agent and an inodilator under current investigation in the treatment of decompensated heart failure. The effects of intravenous levosimendan on the human coronary vasculature, together with myocardial wall stress and oxygen uptake, have not been adequately studied. Methods and Results—Ten adult patients underwent right- and left-heart catheterization. Baseline coronary blood flow was determined with quantitative coronary angiography and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured with a coronary sinus catheter. Echocardiography was performed before and 30 minutes after an intravenous infusion of levosimendan (24-&mgr;g/kg bolus over 10 minutes) was begun. Pulmonary capillary wedge decreased 37% (P=0.009), cardiac output increased 9% (P=0.04), and systemic vascular resistance decreased 18% (P<0.001). Left ventricular ejection fraction increased 20% (P=0.009), and meridional systolic wall stress decreased 48% (P=0.009). Coronary artery diameter increased 10% at 15 minutes (P=0.001) and 11% at 30 minutes (P=0.01). Coronary artery velocity increased 10% over baseline (P=0.04). Coronary blood flow increased 45% (P=0.02), whereas coronary resistance decreased 36% at 30 minutes (P=0.03). Myocardial oxygen extraction decreased 9% at 30 minutes (P=0.04). Conclusions—Levosimendan given intravenously exerts vasodilator effects on human coronary conductance and resistance arteries. Despite a decrease in coronary perfusion pressure, coronary blood flow is increased. A reduction in coronary vascular resistance and a decrease in coronary venous oxygen content indicate primary coronary vasodilation by levosimendan. Improved left ventricular systolic function and decreased myocardial oxygen extraction suggest improved myocardial efficiency.

Accuracy of Doppler-Estimated Pulmonary Vascular Resistance in Patients Before Liver Transplantation

The hyperdynamic circulation associated with cirrhosis is typically characterized by high cardiac output and low systemic and pulmonary vascular resistance (PVR). Approximately 4% of cirrhotic patients develop portopulmonary hypertension, which is an important predictor of hemodynamic instability after orthotopic liver transplantation. Doppler estimation of pulmonary artery systolic pressure (PASP) is used as a screening test for the presence of portopulmonary hypertension. We tested the accuracy of a noninvasive measurement of PVR (ratio of peak tricuspid regurgitant velocity [TRV] to right ventricular outflow tract velocity time integral [VTI RVOT]) to detect increased PVR in a population before liver transplantation. We compared test characteristics of the TRV/VTI RVOT ratio to echocardiographically derived PASP for detection of invasively measured PVR >1.5 Wood units. There was no significant correlation between Doppler-derived PASP and invasively measured PVR. There was a moderate and significant correlation between TRV/VTI RVOT ratio and invasively measured PVR. Compared with Doppler-derived PASP, the TRV/VTI RVOT ratio was a more accurate test for PVR >1.5 Wood units. Using a cut-off value of TRV/VTI RVOT >0.12, the sensitivity and negative predictive value for PVR >1.5 Wood units were 100%. In conclusion, the TRV/VTI RVOT ratio is a more accurate screening test for the presence of portopulmonary hypertension than PASP in patients undergoing orthotopic liver transplantation. Routine use of this ratio may decrease the need for invasive hemodynamic assessment in this patient population.

Multiple causes of left ventricular outflow tract obstruction in a 58-year-old woman.

Figure 1. An M-mode through the right ventricle, aorta, and left atrium showing complete opening and early systolic closure of the aortic valve (arrow) consistent with fixed subaortic obstruction. edema, a paradoxically spilt S2, and a harsh systolic murmur. A transthoracic echocardiogram showed asymmetric septal hypertrophy and a late peaking left ventricular (LV) outflow tract gradient of 137 mmHg. An Mmode showed early systolic closure of the aortic valve leaflets suggestive of fixed subaortic stenosis (Fig. 1). A chord to the anterior mitral valve leaflet was markedly thickened and demonstrated systolic anterior motion. There