International Journal of Cardiology 185 (2015) 148–149
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Dramatic improvement of clinical and hemodynamic parameters of a heart transplant candidate with sildenafil treatment Demet Menekse Gerede ⁎, Tamer Sayın, Veysel Kutay Vurgun, Irem Muge Akbulut, Cetin Erol Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 3 February 2015 Accepted 8 March 2015 Available online 10 March 2015 Keywords: Pulmonary hypertension Treatment Sildenafil Heart failure
Pulmonary hypertension (PHT) is classically defined as an increase in mean pulmonary arterial pressure ≥ 25 mm Hg at rest as assessed by right heart catheterization [1]. It is associated with various clinical conditions. These clinical conditions are classified into five groups. The treatment modalities for group 1 pulmonary hypertension (pulmonary arterial hypertension [PAH]) have diversified enormously in the last decade, including prostanoids, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors. Unfortunately, therapeutic options for group 2 patients (pulmonary hypertension associated with left-sided heart disease) haven't evolved much and the prognosis for this group still remains poor. However, sildenafil has been recently shown to have some acute beneficial effects in patients with left heart failure (HF) in some trials [2]. In this case presentation we discuss a gentleman with advanced left heart failure who showed dramatic clinical and hemodynamic improvement with oral sildenafil treatment. A 55-year-old gentleman was admitted to our clinic for heart failure decompensation. His medical history included coronary artery bypass surgery, an Implantable Cardioverter Defibrillator (ICD) implantation for primary prevention six years later, and an upgrading of his ICD to Cardiac Resynchronization Therapy (CRT) with his ablation due to frequent inappropriate ICD shocks as a consequence of atrial fibrillation. His ejection fraction (EF) was calculated as 25% on transthoracic echocardiographic examination. His peak VO2 value was measured as 12 ml/kg/min via a cardiopulmonary stress test. Due to frequent hospitalizations for decompensation and class 4 symptoms refractory to ⁎ Corresponding author at: Department of Cardiology, Ankara University School of Medicine, Cebeci Heart Center, Cebeci, Ankara 06590, Turkey. E-mail address: [email protected] (D.M. Gerede).
http://dx.doi.org/10.1016/j.ijcard.2015.03.101 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
effective medical therapy, the patient was evaluated as a candidate for heart transplantation. A right heart catheterization (RHC) was performed to determine the patient's eligibility for transplantation. Pulmonary artery pressures and pulmonary vascular resistance were found to be in the ineligible/gray zone (Table 1). Vasoreactivity testing with dobutamine and nasal oxygen was performed to determine the reversibility of the high pulmonary pressures. A partial decrease in pulmonary artery systolic pressure (about 15%) with stable systemic arterial pressure was noted. We decided to add oral sildenafil 50 mg (three times a day) to his ongoing treatment, referring to trials showing beneficial pulmonary hemodynamic effects in patients with advanced heart failure. The patient reported dramatic symptomatic improvement and his New York Heart Association (NYHA) class improved to II from III after the initiation of sildenafil therapy. A follow-up six-minute walk test (MWT) was performed and the result improved to 450 m from 330 m. Three months after the initiation of the therapy, a follow-up RHC was performed, demonstrating dramatic improvement (Table 1). Left heart failure is a common endpoint of many clinical conditions, and despite all the advances in clinical cardiology it still has a high mortality ratio [2]. Some recent studies have investigated the fact that selective inhibition of type 5 phosphodiesterase (PDE5) might have beneficial effects on heart failure [3]. As a result, sildenafil, one of the novel drugs commonly used in the treatment of pulmonary arterial hypertension (group 1), is increasingly being used off-label to treat pulmonary hypertension due to left heart failure. Some trials have shown that oral sildenafil treatment reduced pulmonary vascular resistance, improved exercise performance and peak VO2, and, therefore, reduced breathlessness [4]. It is controversial as to whether the prolonged usage of sildenafil in heart failure patients is associated with harmful effects. Some studies state that hyperkinetic arrhythmias, abnormalities in heart rate and blood pressure, may occur with sildenafil use [4]. In our case, no adverse effects happened due to sildenafil use. We observed the beneficial hemodynamic and clinical effects as stated in the literature. The pulmonary hemodynamic effects of sildenafil were quite dramatic in our patient (Table 1). Our case is important because it is very demonstrative of the beneficial and promising effects of sildenafil in advanced heart failure patients. Classically PAH medications are not indicated in treating PHT with left heart disease (group 2 PHT). The data from studies of using prostanoids and endothelin receptor antagonists to treat heart failure patients have shown that those treatment options have a negative effect. However, sildenafil, a member of a different PAH treatment pathway, may have a role in the given setting. Positive small series and
D.M. Gerede et al. / International Journal of Cardiology 185 (2015) 148–149 Table 1 Right heart catheterization parameters before (02/14) and after (05/14) sildenafil treatment. Parameter
Before sildenafil
After sildenafil
PCWP PAP (systolic/mean) RV (peak systolic/end diastolic) RA Trans pulmonary gradient Cardiac index Pulmonary vascular resistance
34 mm Hg 75/52 mm Hg 75/13 mm Hg 13 mm Hg 18 mm Hg 1.6 lt/min/m2 5.6 wood
23 mm Hg 45/32 mm Hg 45/6 mm Hg 6 mm Hg 9 mm Hg 1.95 lt/min/m2 2.3 wood
PCWP: pulmonary capillary wedge pressure; PAP: pulmonary arterial pressure; RV: right ventricle; RA: right atrium.
case reports have led investigators to initiate larger randomized studies in this setting. The findings of our case dramatically show the benefit of sildenafil therapy for group 2 PHT and this supports the relevant literature with more objective RHC data. Sildenafil may have a role in treating HF patients with low EF and PHT.
149
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] N. Galie, M.M. Hoeper, M. Humbert, A. Torbicki, J.L. Vachiery, J.A. Barbera, M. Beghetti, P. Corris, S. Gaine, J.S. Gibbs, M.A. Gomez-Sanchez, G. Jondeau, W. Klepetko, C. Opitz, A. Peacock, L. Rubin, M. Zellweger, G. Simonneau, ESC Committee for Practice Guidelines. Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT), Eur. Heart J. 30 (2009) 2493–2537. [2] X.D. Zhuang, M. Long, F. Li, X. Hu, X.X. Liao, Z.M. Du, PDE5 inhibitor sildenafil in the treatment of heart failure: a meta-analysis of randomized controlled trials, Int. J. Cardiol. 172 (2014) 581–587. [3] S.R. Goldsmith, Type 5 phosphodiesterase inhibition in heart failure: the next step, J. Am. Coll. Cardiol. 50 (2007) 2145–2147. [4] M. Guazzi, M. Samaja, R. Arena, M. Vicenzi, M.D. Guazzi, Long-term use of sildenafil in the therapeutic management of heart failure, J. Am. Coll. Cardiol. 50 (2007) 2136–2144.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Dramatic improvement of clinical and hemodynamic parameters of a heart transplant candidate with sildenafil treatment Demet Menekse Gerede ⁎, Tamer Sayın, Veysel Kutay Vurgun, Irem Muge Akbulut, Cetin Erol Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 3 February 2015 Accepted 8 March 2015 Available online 10 March 2015 Keywords: Pulmonary hypertension Treatment Sildenafil Heart failure
Pulmonary hypertension (PHT) is classically defined as an increase in mean pulmonary arterial pressure ≥ 25 mm Hg at rest as assessed by right heart catheterization [1]. It is associated with various clinical conditions. These clinical conditions are classified into five groups. The treatment modalities for group 1 pulmonary hypertension (pulmonary arterial hypertension [PAH]) have diversified enormously in the last decade, including prostanoids, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors. Unfortunately, therapeutic options for group 2 patients (pulmonary hypertension associated with left-sided heart disease) haven't evolved much and the prognosis for this group still remains poor. However, sildenafil has been recently shown to have some acute beneficial effects in patients with left heart failure (HF) in some trials [2]. In this case presentation we discuss a gentleman with advanced left heart failure who showed dramatic clinical and hemodynamic improvement with oral sildenafil treatment. A 55-year-old gentleman was admitted to our clinic for heart failure decompensation. His medical history included coronary artery bypass surgery, an Implantable Cardioverter Defibrillator (ICD) implantation for primary prevention six years later, and an upgrading of his ICD to Cardiac Resynchronization Therapy (CRT) with his ablation due to frequent inappropriate ICD shocks as a consequence of atrial fibrillation. His ejection fraction (EF) was calculated as 25% on transthoracic echocardiographic examination. His peak VO2 value was measured as 12 ml/kg/min via a cardiopulmonary stress test. Due to frequent hospitalizations for decompensation and class 4 symptoms refractory to ⁎ Corresponding author at: Department of Cardiology, Ankara University School of Medicine, Cebeci Heart Center, Cebeci, Ankara 06590, Turkey. E-mail address: [email protected] (D.M. Gerede).
http://dx.doi.org/10.1016/j.ijcard.2015.03.101 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
effective medical therapy, the patient was evaluated as a candidate for heart transplantation. A right heart catheterization (RHC) was performed to determine the patient's eligibility for transplantation. Pulmonary artery pressures and pulmonary vascular resistance were found to be in the ineligible/gray zone (Table 1). Vasoreactivity testing with dobutamine and nasal oxygen was performed to determine the reversibility of the high pulmonary pressures. A partial decrease in pulmonary artery systolic pressure (about 15%) with stable systemic arterial pressure was noted. We decided to add oral sildenafil 50 mg (three times a day) to his ongoing treatment, referring to trials showing beneficial pulmonary hemodynamic effects in patients with advanced heart failure. The patient reported dramatic symptomatic improvement and his New York Heart Association (NYHA) class improved to II from III after the initiation of sildenafil therapy. A follow-up six-minute walk test (MWT) was performed and the result improved to 450 m from 330 m. Three months after the initiation of the therapy, a follow-up RHC was performed, demonstrating dramatic improvement (Table 1). Left heart failure is a common endpoint of many clinical conditions, and despite all the advances in clinical cardiology it still has a high mortality ratio [2]. Some recent studies have investigated the fact that selective inhibition of type 5 phosphodiesterase (PDE5) might have beneficial effects on heart failure [3]. As a result, sildenafil, one of the novel drugs commonly used in the treatment of pulmonary arterial hypertension (group 1), is increasingly being used off-label to treat pulmonary hypertension due to left heart failure. Some trials have shown that oral sildenafil treatment reduced pulmonary vascular resistance, improved exercise performance and peak VO2, and, therefore, reduced breathlessness [4]. It is controversial as to whether the prolonged usage of sildenafil in heart failure patients is associated with harmful effects. Some studies state that hyperkinetic arrhythmias, abnormalities in heart rate and blood pressure, may occur with sildenafil use [4]. In our case, no adverse effects happened due to sildenafil use. We observed the beneficial hemodynamic and clinical effects as stated in the literature. The pulmonary hemodynamic effects of sildenafil were quite dramatic in our patient (Table 1). Our case is important because it is very demonstrative of the beneficial and promising effects of sildenafil in advanced heart failure patients. Classically PAH medications are not indicated in treating PHT with left heart disease (group 2 PHT). The data from studies of using prostanoids and endothelin receptor antagonists to treat heart failure patients have shown that those treatment options have a negative effect. However, sildenafil, a member of a different PAH treatment pathway, may have a role in the given setting. Positive small series and
D.M. Gerede et al. / International Journal of Cardiology 185 (2015) 148–149 Table 1 Right heart catheterization parameters before (02/14) and after (05/14) sildenafil treatment. Parameter
Before sildenafil
After sildenafil
PCWP PAP (systolic/mean) RV (peak systolic/end diastolic) RA Trans pulmonary gradient Cardiac index Pulmonary vascular resistance
34 mm Hg 75/52 mm Hg 75/13 mm Hg 13 mm Hg 18 mm Hg 1.6 lt/min/m2 5.6 wood
23 mm Hg 45/32 mm Hg 45/6 mm Hg 6 mm Hg 9 mm Hg 1.95 lt/min/m2 2.3 wood
PCWP: pulmonary capillary wedge pressure; PAP: pulmonary arterial pressure; RV: right ventricle; RA: right atrium.
case reports have led investigators to initiate larger randomized studies in this setting. The findings of our case dramatically show the benefit of sildenafil therapy for group 2 PHT and this supports the relevant literature with more objective RHC data. Sildenafil may have a role in treating HF patients with low EF and PHT.
149
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] N. Galie, M.M. Hoeper, M. Humbert, A. Torbicki, J.L. Vachiery, J.A. Barbera, M. Beghetti, P. Corris, S. Gaine, J.S. Gibbs, M.A. Gomez-Sanchez, G. Jondeau, W. Klepetko, C. Opitz, A. Peacock, L. Rubin, M. Zellweger, G. Simonneau, ESC Committee for Practice Guidelines. Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT), Eur. Heart J. 30 (2009) 2493–2537. [2] X.D. Zhuang, M. Long, F. Li, X. Hu, X.X. Liao, Z.M. Du, PDE5 inhibitor sildenafil in the treatment of heart failure: a meta-analysis of randomized controlled trials, Int. J. Cardiol. 172 (2014) 581–587. [3] S.R. Goldsmith, Type 5 phosphodiesterase inhibition in heart failure: the next step, J. Am. Coll. Cardiol. 50 (2007) 2145–2147. [4] M. Guazzi, M. Samaja, R. Arena, M. Vicenzi, M.D. Guazzi, Long-term use of sildenafil in the therapeutic management of heart failure, J. Am. Coll. Cardiol. 50 (2007) 2136–2144.
