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Response to Inhaled Nitric Oxide, but Neither Sodium Nitroprusside Nor Sildenafil, Predicts Survival in Patients With

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Response to Inhaled Nitric Oxide, but Neither Sodium Nitroprusside Nor Sildenafil, Predicts Survival in Patients With Jachec et al., J Clin Exp Cardiolog 2015, 6:6 Clinical & Experimental Cardiology http://dx.doi.org/10.4172/2155-9880.1000376 Research Article Open Access Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension Wojciech Jacheć1*, Celina Wojciechowska2, Andrzej Tomasik2, Damian Kawecki2, Ewa Nowalany-Kozielska2 and Jan Wodniecki2 1II Katedra i Oddział Kliniczny Kardiologii w Zabrzu Śląskiego Uniwersytetu Medycznego w Katowicach, ul. Skłodowskiej 10, 41-800 Zabrze, Polska 2Department of Cardiology in Zabrze, Medical University of Silesia in Katowice, Poland *Corresponding author: Wojciech Jacheć, II Katedra i Oddział Kliniczny Kardiologii w Zabrzu Śląskiego Uniwersytetu Medycznego w Katowicach, ul. Skłodowskiej 10, 41-800 Zabrze, Polska, Tel: +48 32 373 23 72; Fax: +48 32 271 10 10; E-mail: [email protected] Received date: May 26, 2015, Accepted date: Jun 25, 2015, Published date: Jun 29, 2015 Copyright: ©2015 Jacheć W. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Introduction: Pulmonary hypertension in patients with dilated cardiomyopathy is associated with higher mortality. Objectives: The aim of the study was to assess the predictive value of the vasodilator response to three different drugs, sodium nitroprusside, inhaled nitric oxide, and oral sildenafil, in patients with dilated cardiomyopathy complicated with pulmonary hypertension. Patients and methods: Twenty-nine patients with dilated cardiomyopathy complicated with postcapillary pulmonary hypertension (left ventricle ejection fraction (LVEF) 20.6 ± 8.2%, mean pulmonary artery pressure (mPAP) 42.49 ± 7.27 mmHg, transpulmonary gradient (TPG)>12 mmHg or pulmonary vascular resistance index (PVRI)>5 WU/m2) underwent single-session vaso reactivity testing with sodium nitroprusside, inhaled nitric oxide (120 ppm), oral sildenafil (50 mg), and a combination of sildenafil and inhaled nitric oxide. The vasodilator responders were defined as those participants who achieved a reduction of PVRI<5 WU/m2 and TPG<12 mmHg. The primary study endpoint was death in the 30-month-long follow-up. Kaplan-Meier analysis and Cox proportional hazard modelling were used to identify the predictors of survival. Results: In the follow-up, eight patients died (six patients with irreversible pulmonary hypertension). Six patients underwent successful heart transplantation. Multivariate Cox proportional hazard analysis disclosed a response to nitric oxide as the only predictor of longer survival (HR=11.77, 95% CI=1.12-123.9 at P=0.04). Conclusions: Vasodilator response to inhaled nitric oxide predicts longer survival in patients with dilated cardiomyopathy complicated with pulmonary hypertension. Keywords: Dilated cardiomyopathy; Pulmonary hypertension; (cGMP) in vascular smooth muscle cells, resulting in pulmonary Nitric oxide; Vasodilator response; Survival arteries vasorelaxation [8]. INO administered to patients with heart failure, in contrast to intravenous sodium nitroprusside, reduces Introduction selectively pulmonary vascular resistance without influence on systemic arterial pressure or systemic resistance [9]. Pulmonary hypertension is frequently observed in patients with dilated cardiomyopathy and heart failure. This results from passive Sildenafil citrate, a phosphodiesterase-5 inhibitor, leads to transmission of elevated left ventricle end-diastolic pressure, and accumulation of cGMP, and it has been proven to be selective for eventually reactive pulmonary vasoconstriction occurs [1]. It is pulmonary circulation [10]. A single oral dose of sildenafil has also considered a relative contraindication to cardiac transplantation been proven to be as effective pulmonary vasodilator as iNO, and their listing, if irreversible [2], and is associated with higher mortality and combination synergistically increases cGMP level [11]. morbidity in heart transplant candidates, recipients [3], and other Several papers have concerned the use of various drugs for testing patients [4,5]. of pulmonary hypertension reversibility in a pre-transplant evaluation According to Costard-Jackle et al. [6], and Drakos et al. [7] [12-14]. The results of these studies were inconsistent. Some favored vasoreactivity testing with intravenous sodium nitroprusside in heart either prostaglandin or prostacyclin, and others favored iNO. It is of transplant candidates, identifies a subgroup of patients with excellent note that the major limitation of these studies was the small number of post-transplant prognosis. enrolled patients. Moreover, the issue of the predictive value of vasodilator response in patients with dilated cardiomyopathy Inhaled nitric oxide (iNO), more specific pulmonary vasodilator, complicated with pulmonary hypertension remains unanswered. increases the concentration of cyclic guanosine monophosphate J Clin Exp Cardiolog Volume 6 • Issue 6 • 1000376 ISSN:2155-9880 JCEC, an open access journal Citation: Jachec W, Wojciechowska C, Tomasik A, Kawecki D, Nowalany-Kozielska E et al. (2015) Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension. J Clin Exp Cardiolog 6: 376. doi:10.4172/2155-9880.1000376 Page 2 of 8 Therefore, we designed and conducted this prospective cohort predicting long-term survival in patients with dilated cardiomyopathy study to examine the utility of vasodilator response to three different and pulmonary hypertension. agents and a combination thereof (oral sildenafil and iNO) in All patients (n=29) Survivors (n=21) Deaths (n=8) P Women n (%) 6 (20.7) 5 (23.8) 1 (12.5) NSa Age, years 45.5 ± 8.9 45.58 ± 8.9 45.8 ± 9.6 NSb Duration of disease, years 5.8 ± 3.8 6.34 ± 3.94 4.52 ± 3.19 NSb Diabetes n (%) 3 (10.3) 1 (4.8) 2 (25) NSa Systemic hypertension n (%) 3 (10.3) 3 (14.3) 0 (0) NSa NTproBNP, pg/mL 1599.4 ± 847.3 1507.3 ± 928.4 1758.7 ± 662.9 NSb I–1; II-10; I-1; II-9; II-1; III-6; NYHA class (n) NSa III–15; IV-3 III-9; IV-2 IV-1 Serum sodium, mmol/L 137.2 ± 5.80 137.3 ± 5.67 137.0 ± 6.58 NSb Serum creatinine, mmol/L 82.88 ± 17.73 80.32 ± 18.81 89.56 ± 13.28 NSb LVEDD, mm 71.24 ± 8.0 70.05 ± 8.50 74.75 ± 5.73 NSb LVEDV, ml 230.5 ± 68.5 220.2 ± 73.18 260.63 ± 48.33 NSb LVEF, % 20.6 ± 8.2 22.86 ± 8.83 15.13 ± 3.80 P<0.05b 6-MWT, m 454.1 ± 73.1 449.5 ± 70.42 486.4 ± 66.77 NSb mABP, mmHg 92.26 ± 13.8 93.91 ± 15.08 88.05 ± 9.01 NSb mPAP, mmHg 42.49 ± 7.27 42.07 ± 7.91 43.46 ± 5.64 NSb TPG, mmHg 15.14 ± 4.32 14.37 ± 4.06 17.31 ± 4.44 NSb PAWP, mmHg 27.24 ± 6.31 27.57 ± 7.35 26.14 ± 6.02 NSb PVRI, WU/m2 8.1 ± 3.31 7.53 ± 3.32 9.69 ± 2.71 NSb SVRI, WU/m2 41.6 ± 10.83 41.09 ± 10.50 43.42 ± 11.59 NSb Vasodilator responder n (%): NTP 20/29 (69.0) 16/21 (76.2) 4/8 (50.0) NSa NO 19/29 (65.5) 17/21 (81.0) 2/8 (25.0) P<0.05a SIL 18/29 (62.1) 15/21 (71.4) 3/8 (37.5) NSa SIL/NO 19/29 (65.5) 17/21 (81.0) 2/8 (25.0) P<0.05a Data presented are mean ± standard deviation or absolute numbers with percentage for categorical data. aχ2 test, bMann-Whitney U test LVEDD: Left Ventricle End-Diastolic Diameter; LVEDV: Left Ventricle End-Diastolic Volume; LVEF: Left Ventricle Ejection Fraction; mABP: Mean Arterial Blood Pressure; 6-MWT: 6 Minute Walking Test; NO: Nitric Oxide; NTP: Sodium Nitroprusside; PAWP: Pulmonary Capillary Wedge Pressure; PVRI: Pulmonary Vascular Resistance Index; SIL: Sildenafil, SIL/NO: Combination of Oral Sildenafil and Inhaled Nitric Oxide; SVRI: Systemic Vascular Resistance Index; TPG: Transpulmonary Gradient Table 1: Demographic, echocardiographic and baseline hemodynamic (B-L) characteristics of patients stratified by vital status at completion of follow-up. Patients and Methods between May 2005 and February 2009. We identified 79 patients with pulmonary postcapillary hypertension defined as mPAP>25 mmHg Of 150 consecutive patients with dilated cardiomyopathy and PWP>15 mmHg. Of these patients, we selected 29 patients (6 (idiopathic or post inflammatory) referred for management of heart women) with TPG>12 mm Hg (24 patients) and/or PVRI>5 WU/m2 failure, 111 patients were subject to routine procedure of periodical (5 patients) for enrollment into the study (Table I) [15]. All of the hemodynamic assessment as a part of heart transplantation evaluation J Clin Exp Cardiolog Volume 6 • Issue 6 • 1000376 ISSN:2155-9880 JCEC, an open access journal Citation: Jachec W, Wojciechowska C, Tomasik A, Kawecki D, Nowalany-Kozielska E et al. (2015) Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension. J Clin Exp Cardiolog 6: 376. doi:10.4172/2155-9880.1000376 Page 3 of 8 patients underwent right heart catheterization and a single session of as cardiac index (CI). Systolic (sABP) and diastolic (dBAP) systemic pulmonary artery vasoreactivity testing with sodium nitroprusside, arterial pressure were measured non-invasively. For each examined iNO (120 ppm), and oral sildenafil (50 mg) and repeat inhalation of drug PWP was measured two times, before and after CO nitric oxide. measurements and systemic arterial pressure was measured three times: before, during third and after fifth CO measurements. Other Inclusion criteria were dilated cardiomyopathy (history of heart hemodynamic parameters were acquired five times during each CI failure longer than six months), left ventricle ejection fraction measurement-mean values were used for final evaluation. Acquired LVEF<35%, mPAP at least 25 mmHg supine at rest and no data enabled calculation of mean pulmonary artery pressure (mPAP) angiographic evidence of coronary artery disease.
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