Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension.
ABSTRACT Distal, small-vessel vasculopathy is generally considered a major contributor to the progression of pulmonary hypertension (PH) as chronic thromboembolic pulmonary hypertension (CTEPH) develops over time and is a major determinant of postoperative outcome after pulmonary endarterectomy (PEA). The pathogenesis and natural history of microvascular disease in CTEPH remain uncharacterized. Mechanisms for significant distal disease may involve the following processes: (1) predominant obstructions of "small" subsegmental elastic pulmonary arteries, (2) classical pulmonary arteriopathy of small muscular arteries and arterioles distal to nonobstructed vessels, (3) pulmonary arteriopathy of small muscular arteries and arterioles distal to totally or partially obstructed vessels. Patients in whom obstructed vessels are mainly subsegmental are considered poor surgical candidates. Distal pulmonary vasculopathy in both the occluded and nonoccluded pulmonary vascular bed is characterized by lesions considered typical for idiopathic pulmonary arterial hypertension, including plexiform lesions. The pathogenesis and time course of these vascular lesions remain unclear, but may involve endothelial and/or platelet production and release of mediators and/or altered pulmonary blood flow. The reciprocal contribution of large-vessel (operable) and small-vessel lesions in CTEPH is crucial for the indication and results of PEA. A combination of investigations is used to identify the extent of small-vessel disease, including right-heart catheterization, perfusion lung scan, multidetector spiral computed tomography, pulmonary angiography, and pulmonary arterial occlusion wave-form analysis. Preliminary evidence suggests that medical therapy may provide hemodynamic and clinical benefits for patients in whom PEA cannot be applied, in those who have persistent postoperative PH, or in selected patients with advanced preoperative hemodynamic changes.
Article: Measurement of pulmonary flow reserve and pulmonary index of microcirculatory resistance for detection of pulmonary microvascular obstruction.[show abstract] [hide abstract]
ABSTRACT: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn)) facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn) as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic)/(basal flow)] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressure)x(maximum hyperemic T(mn))]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. Temperature- and pressure-sensor guidewires (TPSG) were placed in segmental pulmonary arteries (SPA) of 13 baboons and intravascular temperature measured. T(mn) and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min) and papaverine (3-24 mg). Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1), supporting T(mn) use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min) & papaverine (to 24 mg) induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn) reductions v baseline, respectively; p<0.0001). PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4), 10(5) & 10(6) microspheres; p = 0.009) and increased PIMR (5.7+/-0.6, 6.3+/-1.0, 6.8+/-0.6 & 7.6+/-0.6 mmHg.sec; p = 0.0048). Thermodilution-derived mean transit time can be accurately and reproducibly measured in the pulmonary circulation using TPSG. Mean transit time-derived PFR and PIMR can be assessed using a TPSG and adenosine or papaverine as hyperemic agents. These novel indices detect progressive pulmonary microvascular obstruction and thus have with a potential role for pulmonary microcirculatory assessment in humans.PLoS ONE 01/2010; 5(3):e9601. · 4.09 Impact Factor
Article: Isolated pulmonary veno-occlusive disease and pulmonary arterial thrombosis in systemic sclerosis – a lethal combination[show abstract] [hide abstract]
ABSTRACT: Arun JeevaganGeneral Medicine, Ipswich NHS Hospital, UKBackground: Isolated pulmonary hypertension secondary to systemic sclerosis is not uncommon. Our patient with systemic sclerosis presented with a very aggressive form of pulmonary hypertension due to a lethal combination of pulmonary veno-occlusive disease (PVOD) and pulmonary arterial thrombosis. This combined presentation has never before been reported in medical literature.Case report: A 75-year-old woman with a 4-month history of atypical chest pains was admitted with a 3-week history of worsening symptoms of shortness of breath, reduced exercise tolerance, and bilateral pitting edema. On examination she had thickened skin in her hands, telangiectasia on her face, maculopapular rash in her legs, raised jugular venous pressure, and bilateral pitting edema. Her autoimmune profile revealed positive anticentromere antibodies, and her echocardiogram showed right ventricular systolic pressure of 91 mmHg. She also had renal impairment secondary to hypoperfusion. A diagnosis of isolated pulmonary hypertension secondary to limited systemic sclerosis was made. As she was clinically improving on slow diuretic infusion and awaiting transfer to a specialist center for management of pulmonary hypertension, our patient died due to cardiopulmonary arrest. Her postmortem revealed that she died of a combination of PVOD and pulmonary arteriopathy due to thrombosis.Conclusion: This is clearly a unique case both in presentation and difficulty of management. Pulmonary vasodilators used in therapy of pulmonary arteriopathy can be detrimental in patients with PVOD. There is no definitive investigation, curative treatment, or management, that exists for a combination of PVOD and pulmonary arteriopathy due to thrombosis secondary to systemic sclerosis.Keywords: pulmonary veno-occlusive disease, pulmonary arterial hypertension, systemic sclerosis, pulmonary arteriopathy with thrombosisInternational Medical Case Reports Journal. 01/2010;
Article: Pulmonary thromboendarterectomy after treatment with treprostenil in a chronic thromboembolic pulmonary hypertension patient: a case report.[show abstract] [hide abstract]
ABSTRACT: In recent years, there has been a major advance in the treatment of pulmonary hypertension. New medications are continually added to the therapeutic arsenal. The prostanoids are among the first agents used to treat pulmonary hypertension and are currently considered the most effective. This case study describes a 63-year-old man who was diagnosed with chronic thromboembolic pulmonary hypertension and successfully treated with subcutaneously administered treprostenil for 6 months before a successful pulmonary thromboendarterectomy. Treatment of chronic thromboembolic pulmonary hypertension often requires a multidisciplinary approach before surgery. Further evaluation of prostanoids is needed to define their role and time of initiation of medical therapy in these patients.International Journal of General Medicine 01/2011; 4:767-72.