Acute hemodynamic effects of nicorandil in patients with primary pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension is managed with vasodilators, and till date no specific drug has been identified with sufficient degree of success. Potassium channels have been implicated in the pathogenesis of primary pulmonary arterial hypertension. We undertook this study to assess the acute effect of oral nicorandil in patients of pulmonary arterial hypertension. METHODS AND RESULTS: We studied acute hemodymanic response of 40 mg oral nicorandil in 10 patients with primary pulmonary arterial hypertension aged between 15 and 39 years (mean age 27.2 +/- 6.7 years). Responders (Group I) were defined as those with > or =20% reduction of pulmonary vascular resistance index and no change or increase in cardiac index; and non-responders (Group II) were those with < 20% reduction of pulmonary vascular resistance index. There were 7 responders (pulmonary vascular resistance index decreased from 22.8 +/- 9.3 to 17.9 +/- 6.5 Wood units) and 2 non-responders (pulmonary vascular resistance index decreased from 26 +/- 3.5 to 25 +/- 1.0 Wood units). The maximum reduction in pulmonary vascular resistance index from baseline was 29.77 +/- 6.53% (23.7-40.5%) in responders and 7.3 +/- 4.2% (4.3-10.3%) in non-responders. The study was halted prematurely in one patient who developed hypotension, requiring intravenous inotropes. CONCLUSIONS: Our results suggest that nicorandil significantly decreases pulmonary artery pressure in primary pulmonary arterial hypertension acutely and can be cautiously tried for the therapeutic use in primary pulmonary arterial hypertension. Further studies are warranted.

Predictors of left atrial appendage clot: a transesophageal echocardiographic study of left atrial appendage function in patients with severe mitral stenosis.

BACKGROUND: The purpose of this study was to prospectively evaluate a large group of consecutive, non-anticoagulated patients with severe rheumatic mitral stenosis and to analyze the left atrial appendage function in relation to left atrial appendage clot and spontaneous echo contrast formation. METHODS AND RESULTS: We prospectively studied left atrial appendage function in 200 consecutive patients with severe mitral stenosis who underwent transesophageal echocardiography and correlated it with spontaneous echo contrast and left atrial appendage clot. The mean age was 30.2 +/- 9.4 years. Fifty-five (27.5%) patients were in atrial fibrillation. Left atrial appendage clot was present in 50 (25%) patients and 113 (56.5%) had spontaneous echo contrast. The older age, increased duration of symptoms, atrial fibrillation, spontaneous echo contrast, larger left atrium, depressed left atrial appendage function and type II and III left atrial appendage flow patterns correlated significantly (p<0.05) with the left atrial appendage clot. Left atrial appendage ejection fraction was significantly less in patients with clot (21.8 +/- 12.8% v. 39.1 +/- 13.2%, p<0.0001) and in those with spontaneous echo contrast (30.3 +/- 16.2 % v. 40.3 +/- 11.8%, p<0.001). Left atrial appendage filling (18.0 +/- 11.7 v. 27.6 +/- 11.8 cm/s, p <0.0001) and emptying velocities (15.4 +/- 7.0 v. 21.5 +/- 9.6 cm/s, p<0.001) and filling (1.4 +/- 1.0 v. 2.5 +/- 1.4 cm, p<0.0001) and emptying (1.5 +/- 1.2 v. 2.1 +/- 1.2 cm, p <0.05) velocity time integrals were also significantly lower in patients with clot as compared to those without clot. On multivariate regression analysis, atrial fibrillation (odds ratio 6.68, 95% CI 1.85-24.19, p=0.003) and left atrial appendage ejection fraction (odds ratio 1.06, 95% CI 1.00 - 1.11, p=0.04) were the only two independent predictors of clot formation. Incidence of clot was 62.59% in patients with left atrial appendage ejection fraction < or = 25% as compared to 10.4% in those having left atrial appendage ejection fraction >25%. Similarly patients with spontaneous echo contrasthadlower filling (21.7 +/- 11.5 v. 29.4 +/- 12.7 cm/s, p<0.0001) and emptying (17.0 +/- 8.1 v. 23.9 +/- 10.9 cm/s, p<0.0001) velocities, as well as filling (1.9 +/- 1.3 v. 2.7 +/- 1.3 cm, p<0.01) and emptying (1.7 +/- 1.0 v. 2.3 +/- 1.4 cm, p<0.01) velocity time integrals as compared to patients without spontaneous echo contrast. In a subgroup of the patients with normal sinus rhythm, the left atrial appendage ejection fraction was significantly less in patients with clot compared to those without clot (31.2 +/- 13.2 v. 41.3 +/- 11.5 %, p<0.01). CONCLUSIONS: In the patients with severe mitral stenosis, besides atrial fibrillation, a subgroup of patients in normal sinus rhythm with depressed left atrial appendage function (left atrial appendage ejection fraction < or = 25%) had a higher risk of clot formation in left atrial appendage and these patients should be routinely anticoagulated for prevention of clot formation.