Irreversible Pulmonary Hypertension Research Articles

Device Closure of a Large Atrial Septal Defect in a Patient with Lung Pathology

The incidence of Atrial Septal Defect (ASD) is approximately 3 per 10,000 live births. Ostium secundum ASD is most common type of ASD accounting for 75% of all ASD cases. Patients with irreversible Pulmonary Arterial Hypertension (PAH) are considered ineligible for shunt closure. It is important to ascertain the cause of PAH particularly to rule out pulmonary cause as in present case. A 56-yearold female patient, known case of Ostium secundum ASD presented with NYHA class IV dyspnea and chest infection. A transthoracic echocardiogram revealed 30 mm ASD with bidirectional shunt, dilated Right Atrium (RA), Right Ventricle (RV), severe Tricuspid Regurgitation (TR) (max PG 85 mmHg) and RV dysfunction. She was intubated and put on mechanical ventilator. CT chest showed right lower lobe bronchiectasis with infective changes. However repeated attempts to wean patient off Bipap support were unsuccessful. Subsequently cardiac catheterization and Balloon Occlusion of ASD revealed Qp/Qs ratio of 8:1 with step up in oxygen saturation of 19%. Mean pulmonary artery pressure was 35 mmHg. Later she underwent successful device closure for ASD with AMPLATZER septal occlude (36 mm) (AGA Medical Corp., Minneapolis, MN, USA). Her physical activity and symptoms were much improved. Follow up transthoracic echocardiography after 5 months revealed normal RV contractility and no PAH. While initially chest infection prevented ASD device closure, underlying bronchiectasis which got worsened by ASD shunt, prevented her from weaning off ventilator. ASD device closure thereby helped to reduce pulmonary blood flow and improvement in lung function enabling her to wean off ventilator support.

(790) - Heterotopic Heart Transplantation in Argentina

The presence of irreversible pulmonary hypertension and/ or anthropometric significant differences between donor and recipient (> 20%) are one of the main constraints in the selection of suitable donors to enable the completion of a successful orthotopic heart transplant. The use of pre-transplant ventricular assistance or the selection of heavier donors, and the heterotopic heart transplantation (HHTx) had been considered in different transplant programs to try to overcome this drawback and also as a bridge to recovery. We present here our experience in HHTx. In an attempt to address this issue we evaluate our experience in 11 HHTx performed at our institution between 2001 and 2013, in 10 patients [8 Males (73 %), 3 Females (27 %); Age 42.5 ± 15 years (18/65)]; one patient (Pts) received a second HHTx at 15 month post first HTxC. Pre transplant diagnosis were: idiopathic dilated cardiomyopathy 7 Pts (63.6%), necrotic dilated cardiomyopathy 1 Pts (9.1%), Chagas cardiomyopathy 1 Pts (9.1%), hypothyroid cardiomyopathy 1 Pts (9.1%) and graft vascular disease 1 Pts (9.1%). Three of the recipients were in national emergency waiting list at the time of transplantation, 2 in urgency and 6 in elective lists. The donor / recipient selection criteria was done taking in account significant high pulmonary vascular resistances and / or anthropometric mismatch, and/or sex mismatch. In all Pts the donor pulmonary artery was anastomosed to the recipient right atrium without the use of any prosthetic material to spare the donor right ventricle and assisting recipient’s left ventricle using the recipient right ventricle to support the pulmonary circulation. Proper synchronization between the two hearts was performed using pacemakers. Ischemic times varied between 76 and 245 minutes (mean 184.1 ± 57.8). Standard immunosuppression scheme was used. The actuarial survival including hospital mortality was 67% at one year and 56% at 5 years. The average follow-up of patients was 4.46 years, and longer survival reached is 13.6 years. All patients who survive more than 3 month returned to normal life. Several attempts to perform HHTx in our country failed using the conventional surgical technic. In our experience, applying the technic described by Yacoub and Khaghani, we consider that is feasible for a selected group of patients with acceptable medium term results.

Pathologic markers for evaluation of reversibility in pulmonary hypertension related to congenital heart disease

To assess the pathologic markers for evaluation of reversibility in pulmonary hypertension (PAH) related to congenital heart disease. Twenty-eight patients with congenital heart disease complicated by PAH were subclassified into reversible pulmonary hypertension (RPAH) and irreversible pulmonary hypertension (IPAH), according to post-operative mean pulmonary artery pressure (MPAP). Pulmonary vascular lesion was analyzed according to Ruan's method. Mean medium thickness percent, mean medium area percent and pulmonary arteriolar density were measured by quantitative morphometry. Immunohistochemical study for transgelin and filamin A was carried out. Amongst the 28 cases studied, 24 were RPAH and 4 were IPAH. Of the 24 patients with RPAH, 13 (54.2%, 13/24) had pulmonary vascular lesion of grade 0, 9 (37.5%, 9/24) of grade 1 and 2 (8.3%, 2/24) of grade 2. Of the 4 patients with IPAH, 1 had lesion of grade 1, 1 of grade 2 and 2 of grade 3. Both preoperative and postoperative MPAP were higher in IPAH patients than that in RPAH patients[(53.3±23.4) mmHg versus (34.1±12.7) mmHg, P=0.020 and (35.0±8.8) mmHg versus (17.8±3.9) mmHg, P<0.01]. Compared to patients with pulmonary vascular lesion of grades 0 and 1, the preoperative MPAP in patients with grades 2 and 3 showed no significant difference, but the postoperative MPAP was higher (P<0.05 or 0.01). Compared to control group, mean medium thickness percent and mean medium area percent were significantly higher in RPAH and IPAH categories (12.0±3.5, 8.5±2.0 versus 5.7±1.0, P<0.01 and 55.8±11.1, 49.0±9.4 versus 34.0±5.5, P<0.01). Mean medium thickness percent was significantly higher in IPAP group than that in RPAH group (12.0±3.5 versus 8.5±2.0, P=0.001). Correlation analysis demonstrated that mean medium thickness percent and mean medium area percent had positive correlation with preoperative and postoperative MPAP. There was no correlation between grading of pulmonary vascular lesion and reversibility. Transgelin and filamin A had stronger staining in pulmonary vascular smooth muscle cells in IPAH than those in RPAH and controls(P<0.05). Pathologic assessment of lung biopsy remains the gold standard for evaluation of the reversibility in PAH related to congenital heart disease. Mean medium thickness percent, mean medium area percent and immunoreactivity for transgelin and filamin A are useful parameters.

The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update

Mandeep R. Mehra, MD (Chair), Charles E. Canter, MD, Margaret M. Hannan, MD, Marc J. Semigran, MD, Patricia A. Uber, PharmD, David A. Baran, MD, Lara Danziger-Isakov, MD, MPH, James K. Kirklin, MD, Richard Kirk, MD, Sudhir S. Kushwaha, MD, Lars H. Lund, MD, PhD, Luciano Potena, MD, PhD, Heather J. Ross, MD, David O. Taylor, MD, Erik A.M. Verschuuren, MD, PhD, Andreas Zuckermann, MD and on behalf of the International Society for Heart Lung Transplantation (ISHLT) Infectious Diseases, Pediatric and Heart Failure and Transplantation Councils

Senning operation as a palliative therapy for a girl with complex heart defect and Eisenmenger syndrome (RCD code: II-1A.4d)

Development of irreversible pulmonary hypertension in D-transposition of the great arteries (D-TGA) with ventricular septal defect (VSD) is a well-known phenomenon. Coexistence of left ventricular outflow tract obstruction (LVOTO) should theoretically protect the patient against pulmonary arterial hypertension (PAH). Application of the Blalock-Taussig shunt (B-TS) temporarily improves condition of the patient, but may contribute to irreversible PAH requiring palliative complex therapy. We present a case of a 18 year-old female with congenital complex heart defect: D-TGA with inflow VSD and subpulmonary stenosis, Eisenmenger syndrome, who was treated with several subsequent palliative cardiosurgical operations, including B-TS and Senning procedure and eventually, combined PAH-specific therapy, what resulted in stabilization of clinical status. JRCD 2016; 3 (1): 14–16

Irreversible pulmonary hypertension associated with Troglostrongylus brevior infection in a kitten

A four month-old kitten was referred at the Veterinary Teaching Hospital of Teramo, Italy. Physical examination, echocardiography, thoracic radiography, copromicroscopy and biomolecular assays led to a diagnosis of severe parasitic bronchopneumonia by Troglostrongylus brevior complicated by pulmonary hypertension. A single administration of a spot on solution containing imidacloprid 10%/moxidectin 1% was effective in stopping larval shedding but clinical, radiographic and echocardiographic signs of bronchopneumonia and pulmonary hypertension still persisted after further follow-ups. While cases of pulmonary hypertension are known in infections by Aelurostrongylus abstrusus, this is the first report of irreversible pulmonary hypertension in a kitten with troglostrongylosis.

The various hemodynamic profiles of the patent ductus arteriosus in adults.

The patent ductus arteriosus (PDA) has diverse clinical and hemodynamic manifestations depending on its size and the degree of the ensuing left-to-right shunt. A small PDA that causes minor shunting has no major hemodynamic consequences. Conversely, a large PDA with a significant left-to-right shunt may lead to various hemodynamic abnormalities. These include left-sided volume overload that may result in heart failure and/or pulmonary hypertension, the latter being a flow-dependent and mostly reversible phenomenon. The most feared complication is the development of severe and irreversible pulmonary hypertension (Eisenmenger physiology). In this manuscript, we provide examples of the various hemodynamic profiles of PDA as assessed by echocardiography in the adult population.

Association study of circulating endothelial cells and clinical outcome of pulmonary hypertension secondary to congenital heart disease

Objective To compare the count of circulating endothelial cells (CECs) between patients with reversible pulmonary hypertension (RPH) and irreversible pulmonary hypertension (iRPH) by flow cytometry in order to find a new biomarker to distinguish RPH from iRPH. Methods Ninety pulmonary hypertension associated with congenital heart disease patients treated in our hospital between September 1, 2013 to March 31, 2014 were enrolled in this study. According to the mean pulmonary arterial pressure (mPAP) measured by echocardiography in six months after treatment, the patients were separated into 2 groups: iRPH group (mPAP≥50 mmHg), RPH group (mPAP<50 mmHg). Results Totally the clinical data of 87 patients were enrolled in the statistic analysis, 86 patients finished the follow-up in 6 months after the surgery, 1 patient died from pulmonary hypertensive crisis. The count of CECs was not correlated with the extent of pulmonary hypertension (P=0.925). The number of CECs was higher in iRPH group than that of RPH group (0.46‰ vs. 0.09‰, Z=-5.021, P=0.000). And also the age of patients in iRPH group was elder than that of patients in RPH group [(43.1±37.4) months vs. (9.3±12.6) months, t=-5.079, P=0.000]. Conclusion The count of CECs is significantly increased in iRPH patients. It could be used as one biomarker to distinguish RPH from iRPH. Key words: Pulmonary hypertension; Congenital heart disease; Circulating endothelial cells; Biomarkers

PATENT DUCTUS ARTERIOSUS: DON’T THROW FLOW UNDER THE BUS

Uncorrected patent ductus arteriosus (PDA) can cause irreversible pulmonary hypertension (PH) with development of Eisenmenger syndrome. Balloon occlusion establishes reversible PH. If balloon occlusion is impractical, vasodilator challenge with inhaled nitric oxide (INO) can demonstrate reversible

Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension

Introduction: Pulmonary hypertension in patients with dilated cardiomyopathy is associated with higher mortality. Objectives: The aim of the study was to assess the predictive value of the vasodilator response to three different drugs, sodium nitroprusside, inhaled nitric oxide, and oral sildenafil, in patients with dilated cardiomyopathy complicated with pulmonary hypertension. Patients and methods: Twenty-nine patients with dilated cardiomyopathy complicated with postcapillary pulmonary hypertension (left ventricle ejection fraction (LVEF) 20.6 ± 8.2%, mean pulmonary artery pressure (mPAP) 42.49 ± 7.27 mmHg, transpulmonary gradient (TPG)>12 mmHg or pulmonary vascular resistance index (PVRI)>5 WU/m2) underwent single-session vaso reactivity testing with sodium nitroprusside, inhaled nitric oxide (120 ppm), oral sildenafil (50 mg), and a combination of sildenafil and inhaled nitric oxide. The vasodilator responders were defined as those participants who achieved a reduction of PVRI<5 WU/m2 and TPG<12 mmHg. The primary study endpoint was death in the 30-month-long follow-up. Kaplan-Meier analysis and Cox proportional hazard modelling were used to identify the predictors of survival. Results: In the follow-up, eight patients died (six patients with irreversible pulmonary hypertension). Six patients underwent successful heart transplantation. Multivariate Cox proportional hazard analysis disclosed a response to nitric oxide as the only predictor of longer survival (HR=11.77, 95% CI=1.12-123.9 at P=0.04). Conclusions: Vasodilator response to inhaled nitric oxide predicts longer survival in patients with dilated cardiomyopathy complicated with pulmonary hypertension.

Anomalous origin of left pulmonary artery from aorta with tetralogy of Fallot in an adult: what is protecting the lung?

Anomalous origin of one-branch pulmonary artery from aorta (AOPA) is a rare congenital anomaly. Uncorrected, it leads to rapid and frequently irreversible pulmonary hypertension. Association with tetralogy of Fallot is very rare and poses a problem of variable pulmonary vascular resistance. Surgical correction involves closure of ventricular septal defect, relief of right ventricular outflow obstruction, and reconstruction of the pulmonary confluence. The AOPA lung appears to be protected from irreversible vascular changes even in adulthood by unknown mechanisms.

Comparison of ambrisentan with sildenafil in congenital heart disease with irreversible pulmonary artery hypertension

Comparison of ambrisentan with sildenafil in congenital heart disease with irreversible pulmonary artery hypertension

HIGH MORTALITY IN THE FISCHER RAT MODEL OF SEVERE PULMONARY ARTERIAL HYPERTENSION LINKED TO STRAIN-SPECIFIC DEFICIENCY IN RIGHT VENTRICULAR ADAPTATION

Inhibition of VEGFR2 with SU5416 (SU), in combination with chronic hypoxia (CH), causes severe, irreversible pulmonary arterial hypertension (PAH) in rats associated with the development of complex intimal and plexiform lesions. In this study, we compared the response of Sprague-Dawley (SD) vs. Fischer rats to SU/CH, to explore the potential importance of genetic Background in the development of the severe PAH phenotype. SU5416 (SU: 20mg/kg), or vehicle (Control), was delivered by subcutaneous injection in 6-week-old Sprague-Dawley (SD, Harlan, USA)) or Fischer rats (CDF, Charles River) followed by a 3-week exposure to CH (10% oxygen). As expected, SU+CH (n=6) resulted in marked RVSP (104± 13 mmHg) or RV hypertrophy (RV/LV+septum: 68±5%) in SD rats; however, all animals survived to 8 weeks. Fischer rats developed a similar severe PAH phenotype in response to SU+CH (RVSP: 102±6 mmHg; RV/LV+septum: 72±6%; NS compared with SD rats) but exhibited high mortality (77%; Figure 1A). At 4 weeks after SU/CH, both Fischer and SD rats showed significant increase in RV wall thickness and decreased PA acceleration time by echo, with no significant differences in RV diameters. However, at 7 to 8 weeks, Fisher, but not SD, rats showed an increase in the ratio of RV internal diameter to LV internal diameter (RVID/LVID), evidence of RV dysfunction, and this was predictive of poor survival in this model (Figure 1B: RVID/LVID in live vs. dead). These data identify important strain differences that impact on the outcomes in a clinically relevant model of severe PAH. Although Fischer rats showed similar hemodynamic responses compared with SD rats in the SU/CH model, they exhibited much higher mortality, possible due to differences in RV adaptation in response to the increased hemodynamic load. Therefore, this model provides a unique opportunity to explore both the mechanisms underlying RV failure and strategies aimed at improving RV adaptation in severe PAH.

Comparación de hallazgos electrocardiográficos y clínicos a la radiografía de tórax en pacientes portadores de CIA con o sin repercusión hemodinámica ecocardiográfica

Background: Atrial septal defect (ASD) is the most frequent congenital heart disease reaching adulthood without diagnosis. It can be presented as a heart anorganic murmur. Some ASD require surgical closure, before irreversible pulmonary hypertension and / or arrhythmias. Objective: Describe imagenologic, electrocardiographic and clinical findings in patient with ASD with or without hemodynamic repercussion. Methods and Materials: We reviewed medical records of patients with echocardiographic ASD in Félix Bulnes Hospital, in a 1 year period. ASD was considered as ≥ 3 millimeters diameter septal defects, without associated heart&#x0D; disease, hemodynamic repercussion was considered as right ventricular enlargement. We also analyzed: reason for referral, sex, age, cardiologic examination, electrocardiography, chest radiography, treatment and outcome. Results: We analyzed 56 patients, 59% female. The median diagnosis age was 5 months. Of the total referral causes, 70% was heart murmur and 30% for other reasons. Ten showed hemodynamic repercussion, most of them referred for heart murmur, 2 for radiological cardiomegaly, 7 had ECG changes. Eight required treatment, three of them surgical. Conclusions: The most common finding in children with ASD diagnosis is heart murmur. Timing on referral is important, especially if the murmur is associated with ECG changes and/or radiological cardiomegaly, because in these cases is more frecuent to find hemodynamic repercution and some may require a faster and specific treatment.

Pulmonary thromboembolism in congenital heart defects with severe pulmonary arterial hypertension

IntroductionCongenital heart defect (CHD) with shunt can lead to severe, even irreversible pulmonary arterial hypertension (PAH); in extreme form to Eisenmenger syndrome (ES). Despite relatively good long-term survival, these patients often suffer from cyanosis and multisystemic dysfunction, where pulmonary artery thrombosis can be a potentially fatal complication. Together with bleeding these are the most frequent causes of non-cardiac death in patients with severe PAH due to CHD. Patients and methodsProspective study of 40 patients with severe PAH due to CHD (28 female/12 male, median age 41.5 years) was performed, with the aim to analyze the presence of pulmonary artery thrombosis and correlating anatomical and laboratory risk factors. ResultsPrevious thrombosis and/or thromboembolic event was found in 7 patients (17.5%). Significant differences in cyanotic vs non-cyanotic patients were in red blood count parameters: median hemoglobin level 195 vs 141 (p<0.0001), median erythrocytes count 6.62 vs 4.88×1012/l (p<0.0001), median hematocrit 0.58 vs 0.44 (p<0.0001). Laboratory findings causing increased risk for thrombosis were increased thrombocytes aggregation in 15 patients (37.5%), hypercoagulation in 5 patients (12.5%) and endothelial dysfunction in 8 patients (20%). Anatomical risk factor—severe pulmonary artery dilatation (>40mm in female and >45mm in male) was found in 19 patients (51.4%). ConclusionsPatients with severe PAH due to CHD represent a high-risk group for pulmonary artery thrombosis with morphological and flow pathology combined with secondary erythrocytosis and coagulation abnormalities. A relatively high incidence of platelet hyperaggregability shown in our study would propose that aspirin therapy might be considered in some highly selected patients with severe PAH due to CHD. Further studies though are needed to support this data.

Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension

Increased pulmonary flow in left-to-right shunt lesions and decreased pulmonary flow and hypoxia in right-to-left shunt lesions constitute the main cause of morbidity and mortality in congenital heart diseases. This study was planned to determine the relation of vasoactive mediators and pulmonary hypertension in congenital heart disease with shunt lesions. Materials and methods: Patients (31 females, 22 males; 5 months to 16 years old) were divided into 2 groups according to their shunt lesions (acyanotic, cyanotic), pulmonary artery mean pressure (below 30 mmHg: nonhypertensive, above 30 mmHg: hypertensive), and pulmonary resistance (below 2 U/m2: low, above 2 U/m2: high). The acyanotic group was further divided into subgroups based on pulmonary artery mean pressure values. Vascular endothelial growth factor, interleukin 6, interleukin 8, fibroblast growth factor, and endothelin levels were determined in systemic arterial, pulmonary artery, and venous blood samples. Results: All vascular endothelial growth factor levels were significantly elevated in the high pulmonary resistance group. Arterial and venous endothelin levels were significantly elevated in the cyanotic group and high pulmonary resistance group. Positive correlations were found between vascular endothelial growth factor and interleukin 6, interleukin 8, and pulmonary artery systolic pressures. Conclusion: Vascular endothelial growth factors play an important role in the development of irreversible pulmonary hypertension; therefore, evaluation of vascular endothelial growth factor levels could guide the management of treatment.

Circulation: Cardiovascular Interventions Editors’ Picks

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Endothelin‐1 as a Mediator and Potential Biomarker for Interferon Induced Pulmonary Toxicity

Endothelin-1 is a potent vasoconstrictor and a therapeutic target in pulmonary arterial hypertension. Endothelial cells are the physiological source of endothelin-1 but in vitro data from our group shows that interferons (IFNα, IFNβ or IFNγ) induce endothelin-1 in pulmonary vascular smooth muscle cells. IFNs are integral to innate immunity and their antiviral and immunomodulatory capability has been harnessed therapeutically; for example, IFNα plays a critical role in the treatment of chronic hepatitis C infection. However, in some patients, IFN causes pneumonitis and possibly irreversible pulmonary arterial hypertension. In this study, we found that of 16 patients undergoing a six-month course of IFNα therapy, two demonstrated considerably increased serum levels of endothelin-1. We propose that IFN therapy results in elevated levels of endothelin-1 in some patients and when clinically significant levels are reached, pulmonary side effects could ensue. This hypothesis can be easily tested in IFN-treated patients by measuring serum endothelin-1 levels and cardiopulmonary physiological parameters.

Percutaneous Ventricular Assist Device in Hypertrophic Obstructive Cardiomyopathy With Cardiogenic Shock: Bridge to Myectomy

We present the case of a 69-year-old woman with end-stage hypertrophic obstructive cardiomyopathy who developed cardiogenic shock. She underwent emergent placement of a percutaneous left ventricular assist device (TandemHeart) in the catheterization lab as a bridge support device until a septal myectomy could be performed as definitive treatment. This case suggests a novel and promising use of the TandemHeart as a bridge to myectomy.

Project 5: Does High Altitude Protect Against Irreversible Pulmonary Hypertension?

Project 5: Does High Altitude Protect Against Irreversible Pulmonary Hypertension?