Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation

Abstract

Objective: To determine the acute vasodilator effect of sublingual sildenafil in heart transplant candidates with severe pulmonary hypertension due to severe left ventricular dysfunction (LVD). Background: Pulmonary hypertension confers an increased risk of early graft failure. Patients and methods: Seven patients, (mean age of 53 F 8) with severe LVD (mean EF: 19 F 1.7%, functional class III -IV) due to coronary artery disease, dilated cardiomyopathy and valvulopathy were evaluated for heart transplant. All patients presented a mean transpulmonary gradient > 12 mmHg and pulmonary vascular resistances >2.5 W.U., despite full treatment for advanced heart failure. The following hemodynamic data were obtained at basal state and then 15, 30 and 45 min after administration of 100 mg of sublingual sildenafil: right atrial, mean pulmonary artery pressure (mPAP), mean pulmonary capillary wedge pressures, mean transpulmonary gradient (mTPG), blood pressure, cardiac output, pulmonary vascular resistances (PVR) and systemic vascular resistances. Sublingual sildenafil was given without changing the previous treatment of heart failure. Results: After 30 min of sublingual sildenafil, mPAP decreased from 37 (28 -61) to 30 (16 -42) mmHg and PVR decreased from 5.2 (1.9 -13.8) to 2.5 (1.4 -3.9) W.U. after 45 min. Mean TPG decreased from 19 (16 -33) to 12 (8 -14) mmHg at 45 min. Mean pulmonary capillary wedge pressure, cardiac output, systemic vascular resistances and mean blood pressure were unchanged. Sublingual sildenafil was well tolerated, with only transient facial flushing in 4 patients and mild headache in 2. Conclusions: Based on this initial study, sublingual sildenafil may be a useful alternative drug to perform acute vasodilator test in heart transplant candidates with significant pulmonary hypertension due to severe LVD. Nevertheless, further studies are warranted to confirm our results.

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

“…changes were accompanied by a reduction in cardiac norepinephrine spillover, a measure of cardiac efferent sympathetic activity. Similar to the recent observations of other groups, we documented a significant reduction in right atrial and mean pulmonary arterial pressure with an accompanying increase in cardiac output [9,10]. The vasodilatory effects of sildenafil were preferentially directed at the pulmonary circulation.…”

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation

“…[9][10][11][12][13] The reversibility of fixed PH by the use of left ventricular assist device (LVAD) support has recently been demonstrated. [14][15][16][17] However, having a less aggressive and simpler therapy to reduce severe PH and allow HT would be of a great value.…”

“…8 Assessment of the reaction of pulmonary hemodynamics to vasodilators has a crucial role in candidate selection. 6,10 Classic pharmacologic tests during right heart catheterization include intravenous milrinone, sodium nitroprusside, inhaled nitric oxide (NO), or iloprost. The American Heart Association guidelines 8 define fixed PH as mean pulmonary artery pressure (MPAP) 4 25 mm Hg and PVR 4 2.5 Wood units (WU) and/or transpulmonary gradient (TPG) 4 12 mm Hg after pharmacologic tests or the continuous administration of inotropic drugs.…”

Sildenafil vs. Nitroprussiato de Sódio durante Teste de Reatividade Pulmonar pré-transplante cardíaco

“…Gómez-Sánchez et al 6 and Freitas Jr. et al 7 have shown that a single dose of 100 mg of sublingual SIL was effective and safe in reducing pulmonary pressure during the PH reversibility test before cardiac transplantation, without significantly interfering with systemic arterial blood pressure. However, during prolonged administration, Katz et al 8 have shown that SIL causes endothelium-dependent Thus, an ideal vasodilator would serve not only to test vascular responsiveness of pulmonary pressure, but would not interfere negatively with systemic circulation, would enhance right cardiac output, and would maintain a sustained reduction in PH.…”