Use of Oral Sildenafil in Patients With Irreversible Pulmonary Hypertension Not Eligible for Heart Transplantation

Gómez-Moreno, S.; Lage, E.; Hernández, Ana; Campos, Ana; Cabezón, Soledad; Ordóñez, Antonio; Hinojosa, R.

doi:10.1016/j.transproceed.2005.02.013

Cited by 18 publications

(7 citation statements)

References 2 publications

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“…16 With regard to its potential to allow for transplantation, it supports and extends to the case report by Gomez-Moreno et al in which a dilated cardiomyopathy patient with a persistently elevate PVR (from Becker muscular dystrophy) failed dobutamine infusion and was treated with four months of sildenafil and later successfully transplanted after lowering PVR to alevel considered acceptable for transplantation. 31 Jabbour et al used sildenafil to lower PVR in potential cardiac transplant patients, although these patients had elevated PCWP and also demonstrated a response to nitrates or prostacyclins. 30 Thus, the degree of persistent PH in these patients could not be quantified.…”

Section: Discussionmentioning

confidence: 99%

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PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Tedford

Hemnes

Russell

et al. 2008

Circ: Heart Failure

173

107

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BACKGROUND Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle (LV) unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A (PDE5A) inhibition would decrease PH in this population. METHODS AND RESULTS We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, one hundred thirty-eight consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure (PCWP), and PH (defined by a pulmonary vascular resistance (PVR) > 3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their PCWP to a value < 15 mmHg (11.8 +/− 2.0 mmHg from baseline 23.2 +/− 6.2 mmHg) one to two weeks after LVAD implantation, but despite this improvement, the PVR of these patients was only minimally affected (5.65 +/−3.00 to 5.39 +/− 1.78 Wood Units). Twenty-six consecutive patients from this group with persistently elevated PVR were started on oral PDE5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth three times per day. The average PVR in the sildenafil treated group fell from 5.87 +/− 1.93 to 2.96 +/− 0.92 Wood Units (P<0.001) and the mean pulmonary artery pressure (mPAP) fell from 36.5 +/− 8.6 to 24.3 +/− 3.6mmHg (P<0.0001) and was significantly lower when compared to the thirty-two LVAD recipients not receiving sildenafil at weeks 12–15 after the initial post LVAD hemodynamic measurements (13 to 17 weeks post LVAD implantation). In addition, hemodynamic measurements of right ventricular (RV) function in sildenafil treated patients was also improved compared with patients not receiving sildenafil. CONCLUSIONS In patients with persistent PH after recent LVAD placement, PDE5A inhibition in this open label trial resulted in a significant decrease in PVR as compared with control patients.

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Section: Discussionmentioning

confidence: 99%

“…30 Several case reports exist in which long term oral sildenafil therapy decreased PVR in a patient with an elevated PCWP to a transplantable level. 31–32 …”

Section: Introductionmentioning

confidence: 99%

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Tedford

Hemnes

Russell

et al. 2008

Circ: Heart Failure

173

107

View full text Add to dashboard Cite

show abstract

“…New approaches based on treatment of heart transplant candidates with pulmonary hypertension have increased the number of patients suitable for placement on the waiting list and additionally it has shown beneficial effect on survival after HTx. Recently, sildenafil, a fosfodiesterase-5-inhibitor and traditional drug for erectile dysfunction treatment, has been successfully introduced into the algorithms for testing and treatment of pre-transplant pulmonary hypertension [14][15][16][17] . Elevated PVR in heart transplant candidates can also be reduced using a left ventricular assist device.…”

Section: Discussionmentioning

confidence: 99%

Impact of pulmonary hypertension on early hemodynamics, morbidity and mortality after orthotopic heart transplantation. A single center study

Bedáňová

Orban²,

Vrsanský³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims.To determine the effect of pre-existing pulmonary hypertension (PHT) on early hemodynamics, morbidity and mortality after heart transplantation (HTx). Methods. Data were prospectively collected from 149 patients, who underwent HTx between January 2000 and December 2007. The subjects were divided into 3 groups: Group A (n=84) without PTH, group B (n=50) with mild to moderate PTH and group C (n=15) with severe PTH. We studied hemodynamic profile, tricuspid valve regurgitation (TR), incidence of acute cellular rejections (AR), infections, duration of hospitalization, 30-day mortality and a longterm survival. Results. Baseline characteristics were similar in all groups. Using vasodilator treatment PVR was successfully brought down to normal range 2.5 ± 0.6 Wood' units (WU) on the day 1 following the surgery in all groups. Over 80% of patients were treated in Group C, 32% in Group A and 46% in Group B. There was no significant difference in the severity of TR among the 3 groups early after HTx (severe TR was observed in 46%, 54%, 33%, respectively). There was no significant difference in incidence of AR (G ≥ 2 Banff classification) (23%, 23%, 33%, respectively), infections (28%, 32%, 33%, respectively) or duration of hospitalization (30, 30, 28 days, respectively). There was no correlation between pre-transplant PHT and 30-day mortality or a long-term survival. Conclusions. In our cohort, PHT dropped very quickly after HTx, and was not associated with acute right heart failure following the surgery. Reversible PTH does not have a negative impact on short-or long-term survival after HTx.

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“…The subsequent reduction in workload of the right ventricle that is observed as a consequence of the drop in pulmonary arterial resistance and pressure raised the possibility that PDE5 inhibitors may also improve the symptoms of right-sided heart failure. Moreover, an early clinical study reported that sildenafil administered to a single BMD patient to improve pulmonary hypertension also led to improved cardiac output [480]. However, subsequent studies have demonstrated that PDE5 inhibitors can directly block cardiac hypertrophy and improve myocardial function by deactivating multiple hypertrophy signalling pathways triggered by pressure load [481].…”

Section: No/cgmpmentioning

confidence: 99%

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

Fairclough

Perkins²,

Davies³

2012

CGT

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DMD is a devastatingly progressive muscle wasting disorder of childhood that significantly shortens life expectancy. Despite efforts to develop an effective therapy that dates back over a century, clinical interventions are still restricted to management of symptoms rather than a cure. The rationale to develop effective therapies changed in 1986 with the discovery of the dystrophin gene. Since then extensive research into both the molecular basis and pathophysiology of DMD has paved the way not only for development of strategies which aim to correct the primary defect, but also towards the identification of countless therapeutic targets with the potential to alleviate the downstream pathology. In addition to gene and cell-based therapies, which aim to deliver the missing gene and/or protein, an exciting spectrum of pharmacological approaches aimed at modulating therapeutic targets within DMD muscle cells through the use of small drugs are also being developed. This review presents promising pharmacological approaches aimed at targeting the primary defect, including suppression of nonsense mutations and functional compensation by upregulation of the dystrophin homologue, utrophin. Downstream of the primary membrane fragility, inflammation and fibrosis are reduced by blocking NF-κB, TGF-α and TGF-β, and free radical damage has been targeted using antioxidants and dietary/nutritional supplements. There are new hopes that ACE and PDE5 inhibitors can protect against skeletal as well as cardiac pathology, and modulating Ca2+ influx, NO, BMP, protein degradation and the mitochondrial permeability pore hold further promise in tackling the complex pathogenesis of this multifaceted disorder.

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Use of Oral Sildenafil in Patients With Irreversible Pulmonary Hypertension Not Eligible for Heart Transplantation

Cited by 18 publications

References 2 publications

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Impact of pulmonary hypertension on early hemodynamics, morbidity and mortality after orthotopic heart transplantation. A single center study

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

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