Refractory Pulmonary Hypertension Research Articles

Heterotopic heart transplantation: the United States experience.

More than 3 decades have passed since the first heterotopic heart transplantation (HHT) was reported. Nowadays, this surgical technique is used rarely, and only in patients who do not qualify for standard orthotopic heart transplantation (OHT). Current indications mainly comprise refractory pulmonary hypertension and a donor-recipient size mismatch (>20%). The objective of this study was to analyze the United States experience with HHT. The United Network for Organ Sharing (UNOS) database between 1987 and 2007 was analyzed. Patients who underwent heart transplantation were enrolled in this study. Patients with missing transplant dates or history of retransplantation were excluded. A total of 41,379 patients underwent OHT and 178 HHT; 32,361 and 111 patients, respectively, were enrolled. Overall 1-, 5-, and 10-year survival was significantly (P < .001) better in OHT (87.7%, 74.4%, 54.4%) than HHT patients (83.8%, 59%, 35.1%). Survival in patients with transpulmonary gradients (TPG) >15 mmHg was 86.6 %, 73.3%, and 57.4% in the OHT and 93.8%, 64.8%, and 48.6% in the HHT group (P = .35). Pretransplant criteria (HHT versus OHT) with statistically significant differences (P < .05) were as follows (mean + SD): recipient weight, 78.9 + 19.9 versus 74.1 + 23.4 kg; recipient height, 174.9 + 13.9 versus 168 + 25.1 cm; and TPG 12.1 + 7.2 versus 9.6 + 6.3 mmHg. The results show that HHT remains a feasible option in a highly selected patient population, with overall good results.

Atrial septostomy in a patient with severe pulmonary hypertension and hypoxia: A therapeutic dilemma

Atrial septostomy may be considered in individuals with severe pulmonary arterial hypertension and right heart failure, despite maximal medical therapy, as a palliative procedure or bridge to transplant. Low oxygen saturation is a relative contraindication to atrial septostomy. However, the majority of the patients with severe refractory pulmonary arterial hypertension for whom atrial septostomy may be indicated have a certain degree of hypoxia. We describe a case of an adult patient with severe pulmonary hypertension and hypoxia, who presented with syncope from reduced left ventricular filling. She subsequently underwent successful atrial septostomy. We extensively discuss the role of atrial septostomy and the management conundrum in such patients.

Vasopressin as a Rescue Therapy for Refractory Pulmonary Hypertension in Neonates

To determine the effect of vasopressin therapy on the efficacy of oxygenation and arterial pressure in infants with severe persistent pulmonary hypertension of the newborn. Retrospective case study. Neonatal ICU, Hospital for Sick Children, Toronto, Canada. Neonates with severe persistent pulmonary hypertension. Intravenous infusion of vasopressin. Ten infants satisfied the inclusion criteria. Inhaled nitric oxide was used for median (interquartile range) duration of 15 hours (11-28 hr) prior to vasopressin commencement. Vasopressin was initiated at a mean dose of 0.0002 ± 0.0002 U/kg/min for a median (interquartile range) duration of 49 hours (13-95 hr). Administration of vasopressin was associated with an improvement in oxygenation index, peak effect 6 hours after drug initiation (p = 0.01), and a reduction in inhaled nitric oxide dose (p < 0.05). There was a concomitant improvement in blood pressure (p < 0.05) and urine output (p < 0.05), without drop in the serum sodium level or worsening in serum lactate level. Although there is limited experience of vasopressin use in persistent pulmonary hypertension of the newborn infants, our case series suggests it to be a potential adjunctive therapy for improving the efficacy of oxygenation and systemic hypotension. A prospective randomized trial is needed to confirm its efficacy and safety in the management of severe persistent pulmonary hypertension of the newborn.

Correction: Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening

Correction: Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening

Методы оценки симпатической активности у пациентов с рефрактерными к лечению системными гипертензиями

Despite the availability of modern medicines for treating the majority of cardiovascular diseases, the existence of such severe diseases as refractory arterial hypertension and pulmonary hypertension, has brought us to the development of the pathogenetic invasive method of such conditions treatment. Identification of potential responses at the stage of patients selection will help us to see in details the pathogenesis and development of this nosology, to determine the predictors of the efficacy of alternative methods of treatment sand to develop the protocol for these situations. From there, the article discusses various methods of activity evaluation of the sympathetic part of the vegetative nervous systemas the mainsector of pathogenesis of systemic hypertension development.

Refractory pulmonary hypertension following extremely preterm birth: paradoxical improvement in oxygenation after atrial septostomy

Refractory pulmonary hypertension following extremely preterm birth: paradoxical improvement in oxygenation after atrial septostomy

An unusual cause of refractory persistent pulmonary hypertension of the newborn: anomalous origin of one pulmonary artery

Persistent pulmonary hypertension of the newborn is a source of considerable mortality and morbidity. Anomalous origin of one pulmonary artery, an uncommon congenital cardiac malformation, is a rare cause of persistent pulmonary hypertension. Here, we report the case of a patient with an anomalous origin of one pulmonary artery from the innominate artery who presented with persistent pulmonary hypertension refractory to treatment.

Potts Shunt in a Child With End-Stage Pulmonary Hypertension After Late Repair of Ventricular Septal Defect

We report on a 10-year-old boy with medically refractory pulmonary arterial hypertension (PAH) and end-stage right heart failure after closure of a ventricular septal defect. The boy was a candidate for lung transplantation (LTX), but an alternative option was to create an Eisenmenger physiology with right-to-left shunting. The shunt could be created either as an intracardiac or as an extracardiac shunt. We decided to create a Potts shunt, a direct anastomosis between the left pulmonary artery and the descending aorta. The Potts shunt functioned as a right-to-left shunt, thus reducing the afterload on the right ventricle. The boy's clinical condition improved markedly, so he was discharged two weeks after the procedure. The ultimate therapeutic option for medically refractory PAH is LTX or heart-lung transplantation, but because of the short life span after LTX, time was bought by postponing the time of transplantation.

Transplantation for Idiopathic Pulmonary Arterial Hypertension

Background— Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described. Methods and Results— Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre– and post–lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post–lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival. Conclusions— The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post–lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival.

Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening

BackgroundPulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.Methods/ResultsCECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.ConclusionCECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.

Left Ventricular Dysfunction after Lung Transplantation in Pulmonary Hypertension Patients

Purpose Lung transplantation is the final treatment option for patients with refractory Pulmonary Hypertension (PH). Unfortunately, short term mortality after lung transplantation amongst these patients is high. Transient Left Ventricular Dysfunction (LVD) is a frequent event on these patients. In review of the literature, there is a paucity of reports of this phenomenon. We describe our experiences at a single institution. Methods and Materials We reviewed our lung transplant database for patients with PH (mean PAP > 25mmHg, Wedge 3 Wood units) who underwent lung transplantation between July 2008 and July 2012. Patients with WHO group 2 PH were excluded. The data was analyzed for peri-operative use of inotropes, IV prostacyclin, RHC/LHC, echocardiographic results, ischemic time, bypass time, PGD, ventilator days, length of stay, and mortality. LVD is defined as wall-motion abnormalities and a drop in EF Results Sixteen patients were identified as having PH. The majority of patients (10) had WHO group 1 PH. Four of the 16 did not have a LHC, while the remaining had no significant coronary artery disease. The mean pre-transplant LVEF was 70% while RVEF was 39%. Thirteen patients were on IV prostacyclin therapy and 6 on inotropes pre-operatively. Four patients (pre-EF 69%) developed LVD post transplant(mean 33%) and all had a return of normal function (post-EF 55%) within 4 months. The number of days on inotropes was on average 1 day longer for the patients with LVD; patients spent one more day on the ventilator and had one grade worse PGD. Conclusions Patients with PH are at high risk of developing LVD. Development of LVD was not associated with greater mortality however there was greater morbidity. The etiology of LVD is unclear but as lung transplantation becomes more common in PH patients, we have to be aware of this potential complication.

Percutaneous Atrial Septostomy with Modified Butterfly Stent and Intracardiac Echocardiographic Guidance in a Patient with Syncope and Refractory Pulmonary Arterial Hypertension

Syncope is associated with poor prognosis in patients with pulmonary hypertension. Atrial septostomy improves cardiac index and functional class in appropriately selected patients with pulmonary hypertension, and has been shown to improve syncope. One of the major challenges to its effectiveness is maintaining septostomy patency. We report the case of percutaneous deployment of a modified peripheral stent to create an atrial septostomy in a man with severe pulmonary hypertension and syncope, initially intolerant of medical therapy. Percutaneous butterfly stent deployment across the interatrial septum using intracardiac echocardiography and fluoroscopy. The patient improved in all clinical parameters (BNP, six-minute walk test, dyspnoea score), and was subsequently able to tolerate targeted pulmonary hypertension therapies. Atrial septostomy using butterfly stents to maintain patency may play a role in the treatment of patients with advanced pulmonary hypertension who do not respond to targeted therapy.

280: Circulating endothelial cell levels decrease after vasodilator therapy and are a biomarker of deterioration in pediatric pulmonary hypertension

Pulmonary vasodilators in general and prostacyclin therapy in particular have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cells (CECs) could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that PAH-specific vasodilator therapy might decrease CEC numbers. We quantified CECs in peripheral blood from children with idiopathic PAH (iPAH, n =30) or PAH secondary to congenital heart disease (PAH-CHD, n =30), before and after treatment and during follow up. CEC were enumerated by immunomagnetic separation with mAb CD146-coated beads. CEC counts were significantly decreased in children after treatment with oral endothelin antagonists and/or PDE5 inhibitors. In 10 children with refractory PAH despite combination oral therapies, SC treprostinil was added and we found a further significant decrease in CEC count during the first month of treatment in every patient. We quantified CEC during 6 to 36 months follow-up after initiation of SC treprostinil and found that CEC count is modified according to clinical status. CEC counts fall with vasodilatator therapy in PAH and could also be used as biomarker of deterioration in refractory pediatric pulmonary hypertension treated with SC treprostinil.

571 Malignant Pertussis in the Young Infant: a Case Report

Infections by bordetella pertussis, has resurged in many countries around the world including developed regions. Where as new vaccination strategies for adolescents, pregnant women and adults have been recommended, mortality...

Variation in the Management of Persistent Pulmonary Hypertension of the Newborn: A Survey of Physicians in Canada, Australia, and New Zealand

Despite advances in management of persistent pulmonary hypertension of the newborn (PPHN), the risk of mortality and adverse neurological sequelae remains high. Characterizing variation in practices is a crucial step toward improved patient outcome. Evaluate intensive care practices in Canada and the Australia-New Zealand region (AUS-NZ). A prospective cross-sectional online survey of neonatologists was conducted. A 35-item questionnaire was developed, validated, and piloted to collect information on diagnosis, inhaled nitric oxide (iNO) practices, alternative vasodilators or cardiotropes, and echocardiography. Variation among survey respondents as well as intergroup comparison was performed. Data were collected from 217 respondents. Echocardiography and arterial blood gas were the most common diagnostic tests to assess the severity of PPHN. iNO administration is more frequently scrutinized in Canada (36% versus 10% [AUS-NZ], p < 0.001). Canadian physicians reported higher use of intravenous milrinone (p < 0.001), vasopressin (p = 0.02), and inhaled prostacyclin (p = 0.02), but lower use of sildenafil (p = 0.01) for refractory pulmonary hypertension. A greater proportion of neonatologists in AUS-NZ were trained to perform echocardiography (p < 0.001) to optimize treatment decisions. Wide variation exists in the management of PPHN. There is a need to provide more guidance regarding principles of management in PPHN, while recognizing the dynamic nature of cardiopulmonary physiology in individual patients.

Mechanical Support for Pulmonary Veno-occlusive Disease: Combined Atrial Septostomy and Venovenous Extracorporeal Membrane Oxygenation

The use of atrial septostomy for refractory pulmonary hypertension and right ventricular failure results in an adequate left ventricular preload and improved cardiac output at the expense of a profound hypoxic shunt. Combined dual-lumen venovenous extracorporeal membrane oxygenation and atrial septostomy provides extracorporeal gas exchange of venous return before the directional right atrial to left atrial shunt, can be deployed percutaneously, and results in an ambulatory patient with stable hemodynamics.

Stage IV sarcoidosis: comparison of survival with the general population and causes of death

The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean ± SD age 48.1 ± 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 ± 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn

Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. Descriptive case report. Genetic department and neonatal intensive care unit of a tertiary care children's hospital. None. We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Mechanical Circulatory Support as a Bridge to Transplant Candidacy

The use of mechanical circulatory support (MCS) in nontransplant eligible candidates remains controversial. Our decision to offer MCS for nontransplant candidates has led to their reevaluation after a period of left ventricular assist device (LVAD) support. From 2001 to September 2009, we had 37 patients who received an implantable LVAD, 22 (59%) were not deemed to be transplant eligible at the time of LVAD insertion (bridge to candidacy, BTC group). Fifteen (41%) patients were considered transplant eligible (bridge to transplant, BTT group) at the time of device insertion and received a HeartMate XVE (n = 7), HeartMate 2 (n = 7), or a Novacor LVAS (n = 1). In the BTC group, patients received the HeartMate XVE device (n = 11), HeartMate 2 (n = 5), or the Novacor LVAS (n = 6). The primary criterion for transplant ineligibility was refractory pulmonary hypertension (PH) in 18 patients, 3 patients did not meet our body mass index criteria (>35 kg/m(2)), and 2 patients were dialysis-dependent. Six (27%) BTC patients died on support. Overall, 16/22 patients (73%) were subsequently listed for transplantation, with one listed for combined heart-lung due to refractory PH. Twelve patients (75%) underwent successful heart transplantation. Three patients died during their transplant. Overall posttransplant survival at one year shows lower survival in the BTC group compared to the BTT group (67% vs. 100%, p = 0.05). At two years and three years the survival was lower, but not statistically different (BTC vs. BTT: 67% vs. 90% and 64% vs. 87%, respectively, p = NS). MCS can successfully convert a large proportion of transplant-ineligible patients into acceptable candidates.

First experience with a paracorporeal artificial lung in a small child with pulmonary hypertension

Stabilizing children with decompensating refractory pulmonary hypertension may require extracorporeal circulatory support. Currently, options in this regard are limited to use of venoarterial extracorporeal membrane oxygenation (ECMO), but this approach is frequently fraught with complications. Alternatively, the interventional pumpless lung-assist membrane ventilator (Novalung GmbH, Heilbronn, Germany) can be used through a femoral artery to femoral vein shunt in patients with end-stage lung disease and hypercapnia or hypoxemia refractory to mechanical ventilation and through a pulmonary artery to left atrium shunt in patients with refractory pulmonary hypertension. The latter configuration has several advantages for children with pulmonary hypertension: (1) It provides a parallel low resistance circuit that drastically decreases right ventricular (RV) afterload and native pulmonary pressure, allowing RV recovery and pulmonary vascular remodeling. (2) It may serve as a long-term pulmonary assist device or as a bridge to lung transplant or a bridge to recovery. (3) It allows physical rehabilitation. Here we report the first successful use of the Novalung surgical lung-assist (sLA) device in a small child with pulmonary hypertension.