Pulmonary Vasodilator Therapy Research Articles

Nonketotic Hyperglycinemia Presenting as Pulmonary Hypertensive Vascular Disease and Fatal Pulmonary Edema in Response to Pulmonary Vasodilator Therapy

The association of pulmonary hypertensive vascular disease with nonketotic hyperglycinemia is rare. We describe 5infants diagnosed with nonketotic hyperglycinemia, in whom pulmonary hypertensive vascular disease was themain presenting feature, and who developed severe pulmonary edema in response to pulmonary vasodilators.

Severe Pulmonary Hypertension in Idiopathic Nonspecific Interstitial Pneumonia

Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD), particularly in idiopathic pulmonary fibrosis (IPF) and ILD associated with connective tissue disease, where the underlying pathology is often a nonspecific interstitial pneumonia (NSIP) pattern. The degree of PH in ILD is typically mild to moderate and radiographic changes of ILD are usually prominent. We describe four patients with idiopathic NSIP and severe PH (mPAP > 40 mmHg). The average mean pulmonary artery pressure was 51±7 mmHg and pulmonary vascular resistance was 13±4 Wood's units. Pulmonary function was characterized by mild restriction (total lung capacity 63–94% predicted) and profound reductions in DLCO (19–53% predicted). Computed tomographic imaging revealed minimal to moderate interstitial thickening without honeycombing. In two of the cases, an initial clinical diagnosis of idiopathic pulmonary arterial hypertension was made. Both were treated with intravenous epoprostenol, which was associated with worsening of hypoxemia. All four patients died or underwent lung transplant within 4 years of PH diagnonsis. Lung pathology in all four demonstrated fibrotic NSIP with medial thickening of the small and medium pulmonary arteries, and proliferative intimal lesions that stained negative for endothelial markers (CD31 and CD34) and positive for smooth muscle actin. There were no plexiform lesions. Severe pulmonary hypertension can therefore occur in idiopathic NSIP, even in the absence of advanced radiographic changes. Clinicians should suspect underlying ILD as the basis for PH when DLCO is severely reduced or gas exchange deteriorates with pulmonary vasodilator therapy.

Inhaled Epoprostenol Therapy for Pulmonary Hypertension: Improves Oxygenation Index More Consistently in Neonates than in Older Children

The purpose of this study was to determine the efficacy of inhaled epoprostenol for treatment of acute pulmonary hypertension (PH) in pediatric patients and to formulate a plan for a prospective, randomized study of pulmonary vasodilator therapy in this population. Inhaled epoprostenol is an effective treatment for pediatric PH. A retrospective chart review was conducted of all pediatric patients who received inhaled epoprostenol at a tertiary care hospital between October 2005 and August 2007. The study population was restricted to all patients under 18 years of age who received inhaled epoprostenol for greater than 1 hour and had available data for oxygenation index (OI) calculation. Arterial blood gas values and ventilator settings were collected immediately prior to epoprostenol initiation, and during epoprostenol therapy (as close to 12 hours after initiation as possible). Echocardiograms were reviewed during two time frames: Within 48 hours prior to therapy initiation and within 96 hours after initiation. Of the 20 patients in the study population, 13 were neonates, and the mean OI for these patients improved during epoprostenol administration (mean OI before and during therapy was 25.6±16.3 and 14.5±13.6, respectively, P=0.02). Mean OI for the seven patients greater than 30 days of age was not significantly different during treatment (mean OI before and during therapy was 29.6±15.0 and 25.6±17.8, P=0.56). Improvement in echocardiographic findings (evidence of decreased right-sided pressures or improved right ventricular function) was demonstrated in 20% of all patients. Inhaled epoprostenol is an effective therapy for the treatment of selected pediatric patients with acute PH. Neonates may benefit more consistently from this therapy than older infants and children. A randomized controlled trial is needed to discern the optimal role for inhaled prostanoids in the treatment of acute PH in childhood.

Therapeutic potential of sildenafil in patients with heart failure and reactive pulmonary hypertension

The PDE5 inhibitor sildenafil belongs to the established and approved therapies in pulmonary arterial hypertension (PAH) [1]. While PAH is a relatively rare disease, pulmonary hypertension (PH) due to left heart disease (postcapillary PH; group 2 of the Dana Point classification) is a frequent phenomenon, particularly in patients with congestive heart failure (CHF) [2]. Importantly, in patients with left heart disease the presence of PH and an impaired right ventricular (RV) function, indicating biventricular heart failure, is associated with a particularly poor prognosis [2]. Targeted PAH therapy is currently not recommended in postcapillary PH [1]. However, in patients with severe CHF who present with impaired RV function and PH despite optimized medical therapy, additional treatment of PH may improve exercise tolerance and outcome. Small uncontrolled studies indicate that sildenafil may be beneficial in patientswith CHF [3,4], but these studies did not consider the severity of PH and the extent of prevs. postcapillary pressure elevation. In this context, the current ESC/ERS guidelines on PH distinguish between passive and reactive postcapillary PH, depending on the transpulmonary gradient (TPG). The therapeutic consequence of this hemodynamic definition remains unclear, however patients with a predominant precapillary component of PH may benefit from targeted therapy. In the context of compassionate care, 9 highly selected patients with biventricular heart failure (LVEF b40%; impaired RV function, defined as TAPSE b17 mm; NYHA class III/IV) and reactive PH (PAPmean ≥25 mmHg), characterized by elevated left ventricular filling pressures (PCWP/LVEDP ≥15 mmHg) and an increased TPG (N12 mmHg) were treatedwith sildenafil (20 mg tid) in addition to pre-existing, guidelineoriented treatment of CHF which had been on a stable dose for at least one month. In all patients, right heart catheterization was performed before and after initiation of sildenafil. Additionally, echocardiographic parameters, serummarkers (NTproBNP) and exercise capacity (6MWD) were recorded. The mean age of the patients was 67.4±2.2 years (range 64–75 years). 7 patients were initially in NYHA class III, 2 patients in NYHA class IV. All patients had received best medical treatment for CHF according to current guidelines (β-blockers, ACE inhibitors and/or AT1-receptor antagonists, aldosterone antagonists, diuretics). The mean follow-up after initiation of sildenafil was 19.7±6.9 weeks. The effects of sildenafil on invasive hemodynamics, echocardiographic parameters, serum markers and exercise capacity are summarized in Table 1. Add-on sildenafil treatment particularly resulted in a significant decrease of PAPmean, TPG and PVR as well as a decrease of PCWP and a trend towards decreased SVR. These hemodynamic changes were associated with an improvement of prognostically relevant parameters including an increase of RV function, decreased right atrial and right ventricular dimensions, a reduction of NTproBNP serum levels, and a substantial improvement of the 6MWD by 91±54m. Consistently, the patients clinical status improved markedly, and there were no significant adverse events. In highly selected patients with CHF, PH and impaired RV function, who were characterized by a predominant precapillary component of PH, the PDE5 inhibitor sildenafil significantly improved clinical symptoms, exercise capacity and prognostically relevant parameters. Although these findings suggest a beneficial effect in this special group of patients, they have to be interpreted with great caution. While the extent of the precapillary component in such patients is highly variable and depends on the volume load, it is important to note that all measurements were performed in fully compensated condition, so that the body weight remained unchanged between the first and follow-up hemodynamic measurements (75.0±6.4 vs. 74.8±6.0 kg, n.s.). Furthermore, previous mortality data exist on the effects of pulmonary vasodilator therapy in patients with CHF. In the FIRST trial, treatment with epoprostenol was associated with a higher mortality compared to placebo [5], indicating that pulmonary vasodilationmay be detrimental in CHF. However, there are important differences between this observation and the findings presented

Response to pulmonary vasodilator treatment in a former smoker with combined interstitial lung disease complicated by pulmonary hypertension: Case report and review of the literature

We describe a 76-year-old former smoker with a diagnosis of combined pulmonary fibrosis and emphysema associated with pulmonary hypertension and rapidly progressive right heart failure, in whom combined treatment with sitaxsentan and sildenafil resulted in sustained improvement of his clinical condition and exercise performance, without any relevant adverse events. Combined pulmonary fibrosis and emphysema comprises a recently identified syndrome, probably related to tobacco use, and characterized by the coexistence of upper-lobe emphysema and fibrotic changes of the lower lobes, preserved lung volumes, significant hypoxemia, and a high prevalence of pulmonary hypertension, resulting in severe dyspnea. To date, no prospective series, to the best of our knowledge, has reported on the effects of pulmonary vasodilator therapy in such patients.

Treatment of segmental pulmonary artery hypertension in adults with congenital heart disease

IntroductionPulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) usually has a homogeneous pressure distribution. More rarely, complex CHD patients have segmental PAH. This is often post-surgically. The characteristics of these patients and their responsiveness to specific pulmonary vasodilator therapy have not been described. MethodsSeven adults with segmental PAH complicating CHD were treated at 3 specialized adult CHD centers between January 2006 and December 2010. Clinical characteristics, six minute walking distances (6MWD), laboratory tests and images were obtained from medical records and the responses to Bosentan, an endothelin-1 receptor antagonist, were assessed. ResultsAll patients (mean age 32 (23–42) years, five females) had a primary diagnosis pulmonary atresia (PA), four with major aortopulmonary collateral arteries (MAPCAs). Four segmental PAH patients had a right pulmonary artery stenosis, two a left pulmonary artery stenosis and one a unilateral MAPCA stenosis. All patients were symptomatic (functional class II or III) and bosentan was started empirically. Bosentan treatment led to a significant improvement in functional class compared to baseline (1.7±0.5 versus 2.4±0.5; p<0.01). Mean 6MWD (available in 6 patients) increased by 62m (22–150m) from 386±135 to 448±133m (p=0.03) after 12months treatment. Most improvement was seen in patients with low baseline 6MWD. Higher baseline exercise heart rate was significantly associated with lesser improvement in 6MWD (r=−0.91 p=0.01). Laboratory results did not change after initiation of bosentan treatment. ConclusionThis small retrospective case series suggested a significant improvement of functional class and exercise capacity after bosentan treatment in patients with segmental PAH. These findings warrant a prospective study of the potential benefit of selective pulmonary vasodilator therapy in these complex patients. Therefore, we call on treating physicians to share similar cases.

The management of pregnancy and pregnancy-related medical conditions in pulmonary arterial hypertension patients

This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2-3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2-3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman.

Longitudinal Shortening Accounts for the Majority of Right Ventricular Contraction and Improves After Pulmonary Vasodilator Therapy in Normal Subjects and Patients With Pulmonary Arterial Hypertension

The right ventricle has a unique contraction pattern, with a greater portion of the shortening occurring in the longitudinal plane. However, the relative contributions of longitudinal and transverse shortening to overall right ventricular (RV) function have not been quantified. We sought to quantify the proportions of longitudinal and transverse shortening to RV function in normal subjects and in patients with pulmonary arterial hypertension (PAH) at baseline and following PAH-specific therapy. The normal cohort comprised 90 subjects with normal clinical echocardiograms, whereas the PAH cohort included 36 patients, of whom 25 had echocardiograms before and after initiation of PAH-specific therapy. Assessment of RV function included tricuspid annular plane systolic excursion, RV fractional area change (RVFAC), and relative change in RV area in longitudinal and transverse planes. Longitudinal fractional area change (LFAC) accounted for the majority of total RVFAC (77% ± 14%) in normal subjects. Among patients with PAH, longitudinal shortening still represented the majority of RVFAC, even though it was less than in normal subjects (63% ± 18%, P < .0001). Following PAH therapy, overall RV function improved (RVFAC, 30% ± 13% to 36% ± 9%; P = .026), solely because of an increase in longitudinal area change. As a result, the proportion of longitudinal shortening increased (LFAC, 58% ± 18% to 69% ± 17%; P = .002), whereas transverse shortening fell (transverse fractional area change, 42% ± 18% vs 31% ± 17%; P = .002). Longitudinal shortening accounts for the majority of RV contraction in normal subjects and patients with PAH, although less so in PAH. Improved RV function following pulmonary vasodilator therapy occurs solely from improvements in longitudinal contraction, suggesting that longitudinal shortening may represent the afterload-responsive element of RV functional recovery.

Pulmonary arterial hypertension and lung transplantation

Transplantation remains the only therapeutic option for selected patients with advanced pulmonary arterial hypertension (PAH) who continue to deteriorate despite optimal pulmonary vasodilator therapy – including intravenous prostanoids and combination therapy. Identification of poor prognostic markers in PAH, including persistence in the New York Heart Association functional class III and IV, and adverse pulmonary hemodynamics at right heart catheterization should prompt early referral for transplantation. There is a need for inclusion of more discriminatory markers of PAH prognosis in donor-lung allocation scores to identify patients at risk and optimize survival to transplantation, given the current shortage of donor organ availability worldwide. Double-lung transplantation is the recommended operation for idiopathic PAH. Heart–lung transplantation is reserved for selected patients with idiopathic PAH with severe right ventricular dysfunction, or congenital heart disease with complex or ventricular septal defect-associated PAH. Novel surgical strategies, including atrial septostomy or the pumpless Novalung® lung assist device with conduits, from the pulmonary artery to the left atrium, can be considered as a bridge to transplant for patients with rapid clinical decline, despite maximal medical therapy. Recent transplant outcomes for PAH are encouraging, albeit with early postoperative risks, a requirement for long-term surveillance, immunosuppression and transplant immunosuppression-specific morbidity.

Recent Advances in Chronic Thromboembolic Pulmonary Hypertension

Surgical excellence in pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH) has begun to spread around the world. The perioperative mortality for this procedure is typically under 10%. The maximal benefit from PTE is derived in those patients who have a high proximal clot burden that is surgically accessible, as outlined by the Jamieson classification. Residual pulmonary hypertension after successful PTE is common and increasingly is managed with maintenance oral pulmonary vasodilator therapy such as endothelin antagonists, phosphodiesterase inhibitors, and/or prostaglandins. The role of pulmonary vasodilator therapy in CTEPH before PTE is limited and should not delay definitive surgical therapy. Although plain deep hypothermic circulatory arrest (DHCA) is the classic technique for CTEPH, alternatives such as DHCA with antegrade cerebral perfusion are feasible as well. Prolonged mechanical ventilation after PTE remains common in part because of reperfusion pulmonary edema. Careful perioperative management can reduce the incidence of this syndrome. Because ventilator-associated pneumonia is also a common complication after PTE, it represents a major opportunity for outcome improvement, particularly because there are multiple modalities for its prevention and prompt diagnosis.

Portopulmonary hypertension: From diagnosis to treatment

Portopulmonary hypertension is a form of pulmonary arterial hypertension that has gained interest in recent years with the development of liver transplantation techniques and new pulmonary vasodilator therapies. Portopulmonary hypertension is defined as pulmonary artery hypertension associated with portal hypertension with or without advanced hepatic disease. Echocardiography plays a major role in screening for portopulmonary hypertension but right heart catheterization remains the gold standard for diagnosis. The treatment of patients with portopulmonary hypertension consists of general measures that apply to all patients that carry the diagnosis of pulmonary hypertension and specific vasodilator therapies. These new therapies showed encouraging results in patients who would otherwise have a contraindication for liver transplantation. The review presents a summary of the current knowledge on the epidemiology, diagnosis, treatment and prognosis of patients with portopulmonary hypertension.

Effects of Pulmonary Vasodilator Therapy on Ventilatory Efficiency during Exercise in Adults with Eisenmenger Syndrome

Eisenmenger syndrome, characterized by systemic-level pulmonary arterial resistance with resultant right-to-left shunt, is associated with low exercise capacity and hyperpnea at rest and exercise. Because ventilatory requirements are augmented by right-to-left shunting, we hypothesized that if pulmonary vasodilator treatment improved pulmonary perfusion in this condition, this would also improve ventilatory efficiency during exercise. To investigate this, data from incremental cardiopulmonary exercise tests performed by Eisenmenger patients before and after beginning therapy with pulmonary hypertension medications were retrospectively analyzed. Setting. Ahmanson/University of California, Los Angeles Adult Congenital Heart Disease Center. Ten adults with Eisenmenger syndrome treated with either bosentan or sildenafil. The primary analysis was comparison, before and after treatment, of the efficiency of exercise ventilation as reflected in the ratio of ventilation (.V(E)) to carbon dioxide output (.VCO₂) measured at the anaerobic threshold (AT), the slope of .V(E)/.VCO₂ during incremental exercise, and end tidal partial pressure of CO₂ (PETCO₂) at the AT. Secondary measures included peak oxygen uptake (.VO₂) and AT. Following treatment there were significant reductions in the slope .V(E)/.VCO₂ (59.5 ± 12.9 vs. 50.0 ± 7.2, P= .003), and significant decrease in .V(E)/.VCO₂ ratio (56.9 ± 6.2 vs. 50.2 ± 5.9, P= .00004) and increase in PETCO₂ (21.12 ± 2.43 vs. 23.9 ± 2.62 torr, P= .0092) measured at the AT. Increases in peak .VO₂ (0.73 ± 0.25 vs. 0.78 ± 0.32 L/min, P= .333) and AT (0.61 ± 0.20 vs. 0.68 ± 0.25 L/min, P= .154) were not significant. These findings are consistent with reduction in right-to-left shunt due to improved pulmonary blood flow, though attenuation of ventilatory drive is not excluded. Treatment of adult Eisenmenger patients with pulmonary the pulmonary vasodilators bosentan or sildenafil leads to improvement in parameters of ventilatory efficiency during exercise.

Portopulmonary hypertension as an indication for combined heart, lung, and liver or lung and liver transplantation: Literature review and case presentation

End-stage liver disease with severe portopulmonary hypertension (PPHTN), which is refractory to vasodilator therapies, is a contraindication for isolated liver transplantation (LT) because of the high mortality rate. Combined heart, lung, and liver transplantation (CHLLT) and combined lung and liver transplantation (CLLT) can be lifesaving options for these patients; however, these procedures have rarely been performed. A 52-year-old man had end-stage liver disease due to hepatitis C and PPHTN; the latter showed a suboptimal response to pulmonary vasodilator therapy with continuous intravenous treprostinil sodium and oral sildenafil citrate and was considered a contraindication to isolated LT. His preoperative left ventricular function was normal, and he had mild to moderate right ventricular dysfunction. He underwent CLLT, which consisted of sequential double-lung transplantation under cardiopulmonary bypass followed by standard LT under venovenous bypass. Re-exploration of the chest cavity was necessary because of bleeding, and respiratory failure developed; however, the patient recovered, was discharged home on day 26, and remained well 1 year after CLLT with the standard immunosuppressants (similar to those used for heart and lung transplantation). For PPHTN, combined thoracic organ and liver transplantation has been reported in only 10 patients. Six of these patients, including our case, underwent CLLT, whereas 4 patients underwent CHLLT. Notably, 2 of the 6 CLLT patients expired within 24 hours of transplantation because of acute right heart failure. CHLLT should be considered for patients with refractory PPHTN. The assessment of preoperative cardiac function is a vital part of the decision to include heart transplantation in CLLT.

Novel Use of Intra-arterial Doppler in the Assessment of Pulmonary Artery Flow Velocities—Observations Before and After Therapy for Pulmonary Arterial Hypertension

Background: Intra-arterial Doppler is a novel technique which enables accurate assessment of blood flow haemodynamics. We evaluated the feasibility of using intra-arterial Doppler for insights into the pulmonary artery flow velocity profile in patients with pulmonary arterial hypertension (PAH), and determined the changes in the flow velocity profile following pulmonary vasodilator therapy. Methods: Intra-arterial Doppler was performed in the pulmonary arteries of seven subjects with PAH before and after six months of Bosentan therapy. The following Doppler derived parameters weremeasured: acceleration time (AcT), systolic ejection time (ET), ratio of acceleration time to systolic ejection time (AcT/ET), systolic velocity time integral (sVTI), diastolic velocity time integral (dVTI) and total velocity time integral (tVTI). Relationships between Doppler parameters and clinical response to Bosentan therapy were analysed. Results: At baseline, all PAH patients displayed a standardised pharmacological treatment and computer assisted, intensified follow-up and treatment titration). Methods: VIPER-BP is a multicentre, open-label, randomisedcontrolled trial inGPclinics throughoutAustralia comparing usual GP management with an intensive BP management strategy using three forms of valsartanbased therapy. The primary endpoint is individualised BP control at six months. Results: During recruitment 2334 patients initially screened. Of these, 2131 (91%) commenced a 28 day valsartan 80mg “run-in” phase. Subsequently, 310 patients achieved their individualBP target (15%)whilst 81patients (5.2%) were rescue randomised. Overall, 1555 patients were randomised to usual care (n= 519) or the VIPER-BP Intervention (n= 1036): comprising 948men (62%) and 607 women (aged 59± 12 vs. 60± 12 years, respectively) and 1004 patients (65%) previously treated for hypertension. Individual BP targets (systolic/diastolic BP) were as follows; 125/75mmHg (18%withproteinuria), 130/80mmHg (55% with diabetes or CVD) and 140/90mmHg (27%). Mean BP at randomisation was 149± 17/88± 11mmHg with similar BP profiles for men and women, respectively (149± 16/88± 11 versus 149± 17/87± 10mmHg). Conclusion:With study completion in August 2011, the VIPER-BP Study will provide invaluable insights into the most effective means to optimise BP levels (on an individualised basis) in the primary care setting.

P86 Cardiovascular system and kidney function after delivery in hypertensive gravidas

Right heart catheterisation is the gold-standard for differentiating pre-capillary pulmonary hypertension (high mean pulmonary artery pressure, normal pulmonary wedge pressure) from post-capillary physiology (elevated pulmonary wedge pressure). The new non-invasive parameter, ePLAR (echocardiographic Pulmonary to Left Atrial Ratio) is calculated from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave:septal mitral annular Doppler Tissue Imaging e′-wave ratio (TRVmax/E:e′).Pulmonary hypertension patients (mean pulmonary artery pressure > 25 mm Hg, n = 133, 66 male, average 65.0 ± 16.8 years) were classified by right heart catheterisation as pre-capillary or post-capillary [subdivided into isolated post-capillary (diastolic pulmonary gradient < 7 mm Hg) or combined pre- and post-capillary cases]. The ePLAR values of these groups were compared to each other and to a population sample of 16,356 population reference echocardiograms.ePLAR values for the normal reference population of 16,356 echocardiograms (age 56 ± 16.6 years) were 0.30 ± 0.09 m/s. Pre-capillary pulmonary hypertension patients (n = 35, 26 male, PAPsys 63.9 ± 16.6 mm Hg, PAPdiast 24.1 ± 7.3 mm Hg, PAPmean 37.9 ± 9.4 mm Hg, PCWP 10.6 ± 2.7 mm Hg) had significantly higher ePLAR values than post-capillary cases (n = 98, 40 male, PAPsys 59.9 ± 17.6 mm Hg, PAPdiast 25.0 ± 7.4 mm Hg, PAPmean 38.1 ± 9.8 mm Hg, PCWP 23.5 ± 6.4 mm Hg) − ePLAR 0.44 ± 0.22 m/s vs 0.20 ± 0.11 m/s (p < 0.001). ePLAR values were significantly lower in isolated post-capillary pulmonary hypertension than in combined pre- and post-capillary cases (0.18 ± 0.08 m/s vs 0.28 ± 0.18 m/s, p < 0.001).ePLAR is a simple echocardiographic parameter which can accurately differentiate the smaller subset of patients with pre-capillary pulmonary hypertension from the more common post-capillary aetiology. The use of this easily obtained echocardiographic parameter has the potential to enhance non-invasive triage of patients for specific pulmonary vasodilator therapy.

P85 Optimising blood pressure assessment in the obstetric day assessment unit

Right heart catheterisation is the gold-standard for differentiating pre-capillary pulmonary hypertension (high mean pulmonary artery pressure, normal pulmonary wedge pressure) from post-capillary physiology (elevated pulmonary wedge pressure). The new non-invasive parameter, ePLAR (echocardiographic Pulmonary to Left Atrial Ratio) is calculated from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave:septal mitral annular Doppler Tissue Imaging e′-wave ratio (TRVmax/E:e′).Pulmonary hypertension patients (mean pulmonary artery pressure > 25 mm Hg, n = 133, 66 male, average 65.0 ± 16.8 years) were classified by right heart catheterisation as pre-capillary or post-capillary [subdivided into isolated post-capillary (diastolic pulmonary gradient < 7 mm Hg) or combined pre- and post-capillary cases]. The ePLAR values of these groups were compared to each other and to a population sample of 16,356 population reference echocardiograms.ePLAR values for the normal reference population of 16,356 echocardiograms (age 56 ± 16.6 years) were 0.30 ± 0.09 m/s. Pre-capillary pulmonary hypertension patients (n = 35, 26 male, PAPsys 63.9 ± 16.6 mm Hg, PAPdiast 24.1 ± 7.3 mm Hg, PAPmean 37.9 ± 9.4 mm Hg, PCWP 10.6 ± 2.7 mm Hg) had significantly higher ePLAR values than post-capillary cases (n = 98, 40 male, PAPsys 59.9 ± 17.6 mm Hg, PAPdiast 25.0 ± 7.4 mm Hg, PAPmean 38.1 ± 9.8 mm Hg, PCWP 23.5 ± 6.4 mm Hg) − ePLAR 0.44 ± 0.22 m/s vs 0.20 ± 0.11 m/s (p < 0.001). ePLAR values were significantly lower in isolated post-capillary pulmonary hypertension than in combined pre- and post-capillary cases (0.18 ± 0.08 m/s vs 0.28 ± 0.18 m/s, p < 0.001).ePLAR is a simple echocardiographic parameter which can accurately differentiate the smaller subset of patients with pre-capillary pulmonary hypertension from the more common post-capillary aetiology. The use of this easily obtained echocardiographic parameter has the potential to enhance non-invasive triage of patients for specific pulmonary vasodilator therapy.

Repair of Atrial Septal Defect With Eisenmenger Syndrome After Long-Term Sildenafil Therapy

We report a woman with atrial septal defect and severe pulmonary hypertension with 25.0 Wood unit.m(2) of indexed total pulmonary vascular resistance. She underwent successful corrective repair of atrial septal defect after 2 years of treatment with sildenafil, and has been monitored for 4 years after repair. This case supports a "treat and repair" approach using advanced pulmonary vasodilator therapy in selected patients with inoperable severe pulmonary hypertension associated with atrial septal defect.

Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis

We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil.

Does pulmonary air embolism affect the pulsatility of pulmonary capillary blood flow in dogs?

The difference in the uptake rate through the lungs between nitrous oxide and oxygen has been shown to represent the pulmonary capillary blood flow (Qc). The pulsatility of Qc, defined as the ratio of maximum Qc and mean Qc (Qc max/Qc), the ratio of Qc max and stroke volume (Qc max/SV), and the ratio of systolic Qc and SV (Vsyst/SV), has been also shown to indicate the pulmonary vasodilation as well as vasoconstriction. We measured Qc by means of body plethysmography in dogs with pulmonary air embolism, in order to evaluate its effect on the pulmonary vasculature. Ten adult dogs were anesthetized with pentobarbital and pancuronium, and were mechanically ventilated. A volume of air (0.5 ml/kg) was injected into the central vein. Although there was no significant change in systemic blood pressure, cardiac output, heart rate, and airway pressure after the injection of air, pulmonary arterial pressure and pulmonary vascular resistance increased significantly. Qc, Qc max, Qc max/Qc, and Qc max/SV decreased significantly after the air injection. Since these findings suggest that the pulmonary air embolism provoked pulmonary vasoconstriction, and attenuated the pulsatility of Qc, optimal pulmonary vasodilation therapy would be recommended to improve the pulmonary hypertension secondary to pulmonary air embolism.

Initial Experience with Sildenafil, Bosentan, and Nitric Oxide for Pediatric Cardiomyopathy Patients with Elevated Pulmonary Vascular Resistance before and after Orthotopic Heart Transplantation

Background. Although pulmonary hypertension complicating dilated cardiomyopathy has been shown to be a significant risk factor for graft failure after heart transplantation, the upper limits of pulmonary vascular resistance (PVR) that would contraindicate pediatric heart transplantation are not known. Methods. A retrospective review of all pediatric orthotopic heart transplant (OHT) performed at our institution from 2002 to 2007 was performed. Seven patients with PVR > 6 Wood's units (WU) prior to transplant were compared pre- and postoperatively with 20 matched controls with PVR < 6 WU. All pulmonary vasodilator therapies used are described as well as outcomes during the first year posttransplant. Results. The mean PVR prior to transplantation in the 7 study cases was 11.0 ± 4.6 (range 6–22) WU, compared to mean PVR of 3.07 ± 0.9 WU (0.56–4.5) in the controls (P = .27 × 10−6). All patients with elevated PVR were treated pre-OHT with either Sildenafil or Bosentan. Post-OHT, case patients received a combination of sildenafil, iloprost, and inhaled nitric oxide. All 7 case patients survived one year post-OHT, and there was no statistical difference between cases and controls for hospital stay, rejection/readmissions, or graft right ventricular failure. Mean PVR in the cases at one and three months post-OHT was not significantly different between the two groups. Only one of the cases required prolonged treatment with iloprost after OHT. Conclusions. A PVR above 6 WU should not be an absolute contraindication to heart transplantation in children.