Recurrent Pulmonary Hypertension Research Articles

Effect of Sildenafil on Pulmonary Artery Pressure, Systemic Pressure, and Nitric Oxide Utilization in Patients With Left Ventricular Assist Devices

Pulmonary artery hypertension can complicate the early postoperative care of patients with left ventricular assist devices (LVADs). Inhaled nitric oxide (INO) is frequently used to manipulate pulmonary resistance after LVADs have been placed. We evaluated the effect of oral sildenafil therapy on pulmonary artery pressure, systemic pressure, and nitric oxide utilization. After Institutional Review Board approval, the records of 10 consecutive adult patients with LVADs and pulmonary hypertension who received sildenafil were reviewed. Demographics, surgical history, INO use, inotrope requirements, and hemodynamic response to oral sildenafil at multiple intervals were collected. Hemodynamic data were analyzed with a two-way analysis of variance of repeated measures with correction for multiple comparisons. There were 8 men and 2 women with 6 Heartmate XVE LVADs and 4 Thoratec LVADs (both, Thoratec, Pleasanton, California). When weaning was attempted, 8 patients who received INO demonstrated rebound pulmonary hypertension or increased right heart dysfunction. All patients were on inotropic therapy with dobutamine and milrinone. Sildenafil produced a significant reduction in pulmonary artery systolic pressure within 90 minutes of oral administration (p = 0.042). Significant changes in systolic blood pressure, mean arterial pressure, systemic vascular resistance, and heart rate were not observed. All 8 patients receiving INO were weaned within 12 hours without recurrent pulmonary hypertension. All 10 patients were weaned from inotropic support within 72 hours. No patient suffered right-side heart failure requiring intervention. Oral sildenafil represents a useful adjunctive therapy for patients with LVADs. In our series, it provided additional reduction of pulmonary artery pressure, and facilitated weaning from INO and inotropes without deleterious hemodynamic consequences.

Goals and guidelines for treating hypertension in a patient with heart failure

Hypertension promotes left ventricular (LV) hypertrophy and myocardial remodeling and is frequently present in patients with systolic or diastolic heart failure. Control of hypertension in both of these settings may attenuate progressive LV hypertrophy and remodeling and improve clinical outcomes. Guidelines for the management of heart failure recommend that hypertension should be treated in all patients with preclinical heart failure as well as in those with heart failure with reduced or preserved LV systolic function. Consistent with national hypertension guidelines, the goal for blood pressure control in hypertensive patients with heart failure is less than 140/90 mm Hg, but lower targets (< 130/80 mm Hg) may be desirable in those with concomitant diabetes mellitus or renal disease. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and beta-adrenoreceptor antagonists are first-line options for hypertension treatment in heart failure. Calcium channel antagonists and the alpha blocker doxazosin should be avoided. Episodes of recurrent pulmonary edema and hypertension may also indicate underlying severe renovascular disease that may respond to percutaneous renal artery intervention.

Preoperative ECMO in Transposition of the Great Arteries With Persistent Pulmonary Hypertension

Persistent fetal circulation in transposition of the great arteries results in severe persistent pulmonary hypertension, which increases the risk of early mortality. We report the case of a newborn with transposition of the great arteries and intact ventricular septum associated with pulmonary hypertension. After the failure of immediate balloon atrial septostomy and supportive therapy including inhaled nitric oxide, preoperative extracorporeal membrane oxygenation reversed pulmonary hypertension and ventricular insufficiency and preceded a safe, delayed, cardiac surgical procedure. Unlike the authors of the other few case reports on this subject, we recommend a preoperative stabilization period after discontinuation of extracorporeal membrane oxygenation to avoid left ventricular "deconditioning" and postoperative deterioration related to recurrent persistent pulmonary hypertension.

Moving to a slow beat

A 70-year-old woman with a history of recurrent atrial fibrillation and pulmonary hypertension became increasingly fatigued over the course of several days. Treatment with amiodarone was discontinued about 3 weeks earlier when her atrial fibrillation was deemed to be chronic. Her pulse was in the 30s, prompting an immediate ECG.

Recurrent pulmonary embolism and pulmonary hypertension in chronic tetraplegia

Case report. To describe an unusual case of progressive pulmonary hypertension due to recurrent pulmonary embolism in a chronically paralyzed spinal cord injury patient. Veterans Administration Hospital, West Roxbury, MA, USA. A 57-year-old man, tetraplegic, sensory incomplete and motor complete for 30 years due to a diving accident, complained of lightheadedness and shortness of breath intermittently for 7 years. Examination during the latest episode revealed anxiety, confusion, respirations 28 per min, blood pressure 80/60 mmHg, and arterial pH 7.41, P(CO2) 28 mmHg, P(O2) 95 mmHg on 2 l of oxygen. A chest film 2 weeks earlier had revealed a right-sided cutoff of pulmonary vasculature; the current film showed right-sided pleural effusion. Review of EKGs showed a trend of increasing right axis deviation with recovery and recurrences during the previous 9 years and a current incomplete right bundle branch block with clockwise rotation and inverted T waves in V1-4. Computerized tomography with contrast material revealed small pulmonary emboli, but only in retrospect. The patient died shortly after scanning. The pulmonary arteries were free of thromboemboli on gross examination but medium and small-sized arteries were constricted or obliterated with thrombotic material microscopically. The estimated ages of the thromboemboli ranged from days to years. The right ventricle was hypertrophied; the coronary arteries were patent. Recurrent pulmonary emboli resulted in chronic pulmonary hypertension and eventual death in a patient with chronic tetraplegia.

Antiphosphatidylethanolamine antibodies contribute to the diagnosis of antiphospholipid syndrome in patients with systemic lupus erythematosus

Objective: To evaluate the correlation between antiphosphatidylethanolamine antibodies (aPE) and some antiphospholipid antibodies (aPL)-related clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods: Patients with SLE (n = 217) were tested for the presence of aPE, anticardiolipin antibodies (aCL), and lupus anticoagulant (LA). The prospective aPL-related clinical manifestations studied were: thrombosis, thrombocytopenia, recurrent fetal losses, heart valvulopathies, hemolytic anemia, livedo reticularis, and pulmonary hypertension. Results: A total of 109 SLE patients (50.23%) were IgG aPE-positive; 17.51% presented aPE as the sole autoantibody and had some clinical features of aPL-related clinical manifestations. IgG aPE were associated to the presence of heart valvulopathies (p = 0.002). A statistical difference was also found when considering high levels of IgG aPE (O.D.> 0.600) in patients with livedo reticularis (p = 0.008). Conclusion: The evaluation of IgG aPE may allow us to detect some more patients with aPL-related clinical manifestations in the SLE population. aPE correlated particularly with valvulopathies and livedo reticularis.

Reoperative pulmonary thromboendarterectomy

Background. Recurrent symptomatic pulmonary hypertension is uncommon after primary pulmonary thromboendarterectomy (PTE). We reviewed our experience with patients undergoing repeat PTE to determine the risk factors for recurrent disease, and the selection criteria, relative risks, and functional outcomes of reoperative PTE.Methods. Since 1990, 13 of 870 (1.5%) patients underwent reoperative PTE at our institution. These 7 men and 6 women (mean age 38.6 years) were contrasted with the most recent 225 patients (111 men, 114 women, mean age 52.7 years) who underwent primary PTE for whom complete hemodynamic data are available. The preoperative evaluation of all patients was similar. Pulmonary hemodynamic data and outcome measures were compared between groups.Results. Of 13 reoperated patients: 69% (9/13) had their primary operation at another institution, 54% (7/13) initially underwent unilateral PTE, 38% (5/13) had identifiable coagulation disorders, 38% (5/13) had ineffective caval filtration, 31% (4/13) had suboptimal anticoagulation management, and 31% (4/13) had complete unilateral pulmonary artery obstruction. The mean interval to reoperation was 5.2 years (range 0.7 to 10.9 years). All control patients underwent bilateral PTE using hypothermic circulatory arrest. Operative mortality was 7.7% (1/13) with reoperation vs 8.4% (19/225) in controls. No difference (p = NS) was observed between groups in the preoperative pulmonary artery pressure (PAP) or pulmonary vascular resistance; however, the control group had a significantly (p < 0.05) greater reduction in the postoperative PAP (46/19, mean 28 mm Hg vs 59/23, mean 35 mm Hg) and PVR (271 ± 172 vs 399 ± 154 dynes/s/cm−5) compared with the redo group. No substantial difference in morbidity or functional outcomes was observed between groups.Conclusions. Reoperative PTE can be performed with a perioperative risk comparable with primary PTE, although the improvement in pulmonary hemodynamics is not as favorable. Bilateral primary operation, effective caval filtration, and vigilant anticoagulant management would prevent the need for most reoperative PTEs.

Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia

Background/Purpose: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension.Methods: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's t test. A P value of less than .05 was considered significant.Results: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 ± 8.4 mm Hg to 58.4 ± 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension.Conclusions: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a therapy. A multicenter prospective trial is advocated.

Recurrence of pulmonary hypertension after ventricular septal defect closure and perioperative response to nitric oxide

The ability of inhaled nitric oxide to reduce pulmonary vascular resistance is currently used to select borderline patients for reparative surgery and to treat postoperative crises of pulmonary hypertension. A case of an infant with non-restrictive VSD who classified as a nitric oxide responder both in the catheterization laboratory and after surgery, but developed recurrent pulmonary hypertension is described. The limitations of inhaled nitric oxide in predicting the natural history of successfully operated patients are discussed.

The Use of a Second Course of Extracorporeal Membrane Oxygenation in Neonatal Patients

Extracorporeal membrane oxygenation (ECMO) has been successful in rescuing near term or term infants in cardio-respiratory failure that results from a reversible disease process. In most cases, only one course of ECMO is needed to save these infants. However, a second course of ECMO may be beneficial in a select group of infants when recurrent persistent pulmonary hypertension develops. Other than abstract form, this is the first report of the use of a second course of ECMO in the literature. The authors report on three infants, two with recurrent persistent pulmonary hypertension secondary to congenital diaphragmatic hernia and one with necrotizing tracheobronchitis after Group B streptococcal sepsis who were treated at their institution with a second course of ECMO. Technical considerations in using a second course of ECMO depend upon the initial vessel cannulation site, time elapsed between cannulations, and the condition of the original artery and vein. By adopting a stenting procedure in those infants whose initial trial off was equivocal, a second cannulation may be prevented in neonatal patients with recurrent persistent pulmonary hypertension.

Nitric oxide avoids the need for a second course of ECMO in congenital diaphragmatic hernia

Inhaled nitric oxide was effectively used to avoid the need for a second course of extracorporeal membrane oxygenation (ECMO) in a neonate with a congenital diaphragmatic hernia and recurrent pulmonary hypertension following ECMO.

Evaluation of pulmonary hypertension in biopsies of the lung

The most common reasons for biopsy in the evaluation of pulmonary hypertension are to establish the diagnosis of primary pulmonary hypertension, and to determine the grade and reversibility of arterial changes in children with congenital heart disease. Optimal evaluation of lung biopsies for vascular disease entails adequate fixation and staining for clastic tissue, adequate sampling, and a complete clinical history. Virtually all of the changes of pulmonary hypertension are non-specific, and include plexiform lesions, dilatation lesions, arteritis, intimal thickening, and medial hypertrophy. The significance of thrombosis in primary pulmonary hypertension, and the distinction between recurrent thromboembolism and thrombotic primary pulmonary hypertension remain controversial. Primary pulmonary arterial hypertension is a diagnosis of exclusion, and is associated with portal hypertension and autoimmune disease in a minority of cases. The most common form of idiopathic post-capillary pulmonary hypertension is pulmonary veno-occlusive disease, which is occasionally associated with chemotherapy and bone marrow transplantation. The pathologist must be aware of a host of secondary forms of precapillary pulmonary hypertension, including congenital heart disease, chronic major vessel thromboembolic pulmonary hypertension, hypoxia, interstitial lung disease, haematologic disorders, talc emboli, and tumour emboli, and a host of post-capillary lesions, including acquired heart disease, sarcoidosis, mediastinal disease, and cardiac tumours.

Timing of repair of congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation support

Treatment of congenital diaphragmatic hernia (CDH) has undergone a revolutionary change in philosophy, from previous urgent repair to the present practice of stabilization and delayed repair. However, when extracorporeal membrane oxygenation (ECMO) is required, many people believe that the risk of postoperative pulmonary hypertension (PPHN) mandates hernia repair while on ECMO. This report details the experience in two ECMO centers with stabilization, ECMO if required, and CDH repair post-ECMO. All CDH patients symptomatic in the first hour of life with a gestational age of at least 34 weeks during the period were reviewed retrospectively. Standard criteria were used to select patients for ECMO. High-frequency jet or oscillating ventilators and nitric oxide were not routinely available throughout the study period, but were used in some of the more recent patients. A total of 60 patients presented to the two centers; 24 cases were stabilized with conventional management, repair of the CDH was done elective, and survival was 100%. Eight patients were referred after having repair elsewhere; six survived (75%). The two deaths were attributable to associated lethal lesions-complex cyanotic heart disease and alveolar capillary dysplasia. Eight patients who required ECMO were managed with the intention of repairing the defect on ECMO. Four survived (50%). Two patients died before repair. Twenty patients were managed with ECMO, with the intention of repairing the defect after decannulation. Overall survival was 13 (65%), deaths were caused by pre-ECMO hypoxia, pulmonary insufficiency, and associated cardiac disease. No patient had recurrent pulmonary hypertension after late repair. The incidence of operative complications and the requirement for blood transfusion were significantly lower for the patients who had repair after ECMO. Overall, 47 of the 60 patients survived (78%). The results compare favorably with those of previous studies and the authors recommend that children with CDH be managed with a protocol of initial stabilization, ECMO if required, and repair of the CDH after decannulation.

Nitric oxide reversal of recurrent pulmonary hypertension and respiratory failure in an infant with CDH after successful ECMO therapy

Nitric oxide (NO) represents a new therapeutic modality for treating neonatal pulmonary hypertension and may obviate the need for extracorporeal membrane oxygenation (ECMO) in a number of cases of neonatal respiratory failure. Recently, the authors treated an infant with a congenital diaphragmatic hernia and pulmonary hypertension with NO on two separate occassions. During the initial period of stabilization, NO failed to reverse the pulmonary hypertension and prevent the development of progressive respiratory failure. After a successful course of ECMO, recurrent pulmonary hypertension developed that was successfully treated with continuous low-dose NO therapy for over 1 month. Prolonged administration of NO in varying doses titrated to clinical and echocardiographic parameters was well tolerated by the infant and prevented the need for a second run of ECMO.

Experience with delayed repair of congenital diaphragmatic hernia during extracorporeal membrane oxygenation in a European center

In high-risk patients with congenital diaphragmatic hernia (CDH), we conducted a strategy of delayed repair following preoperative stabilization, including ECMO if necessary. From January 1991 to July 1992, preoperative ECMO treatment was delivered to 6 out of 14 high-risk patients with CDH. In this study, we report our experience with this policy of preoperative stabilization in six ECMO-treated patients in whom the diaphragmatic defect was repaired on ECMO. In all patients bleeding complications occurred. Three of the six ECMO-treated patients died, in two cases due to recurrent persistent pulmonary hypertension. Overall mortality was 43%.

A case report of unilateral absence of left pulmonary artery.

The Unilateral absence of a pulmonary artery (UAPA) is an uncommon congenital anomaly. Approximately 160 cases have been reported in the literature since Frantzel's first report in 1968. Most of the patients with UAPA are asymptomatic but some patients may suffer from recurrent respiratory infections, hemoptysis, or pulmonary hypertension. The diagnosis could be suspected from the chest roentgenogram and lung scan, and definitely confirmed by pulmonary angiography. We experienced a case of UAPA in a 39-year-old male with the recurrent hemoptysis. Chest X-ray revealed that the left lung volume was moderately decreased and the heart and mediastinum were displaced to the left side. Lung perfusion scan showed that the left lung was not perfused. Pulmonary angiography revealed the absence of the left main pulmonary artery. Aortic arch and descending aorta on aortogram were right sided. Blood supply to the left lung was originated from numerous systemic collaterals from intercostal and brachiocephalic origin. No other intrinsic or internal abnormalities of the cardiac chambers were noted.

Antiphospholipid Antibodies and Arterial Thrombosis

Antiphospholipid antibodies are a relatively heterogeneous mix of immunoglobulins with binding specificities for negatively charged or neutral phospholipids. Currently, the most commonly detected antiphospholipid antibodies include the anticardiolipin antibody, the lupus anticoagulant, and an antibody implicated in false-positive VDRL testing. Recently, a clinical syndrome of vaso-occlusive disorders associated with antiphospholipid antibodies has been identified and may result from immune-mediated disruption of endothelial function. This clinical syndrome encompasses arterial and venous thrombosis, recurrent fetal loss, neurologic dysfunction (eg, migraine, chorea, and encephalopathy), systemic and pulmonary arterial hypertension, and endocardial disease. Although most commonly associated with systemic lupus erythematosus, the antiphospholipid antibody syndrome also has been identified in patients with vaso-occlusive disease without systemic lupus erythematosus. Recently, identification of antiphospholipid antibodies has been facilitated by the development of a more sensitive assay for anticardiolipin antibody. In this article, case histories of three patients with arterial thrombosis and associated anticardiolipin antibodies, including the first associated case of terminal aortic thrombosis, are reviewed and the subject of the antiphospholipid antibody syndrome is discussed.

Recurrent pulmonary arterial hypertension following neonatal treatment with extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and cardiac support to neonates with life-threatening persistent pulmonary arterial hypertension unresponsive to other therapies (1, 2). After ECMO treatment, ≥80% of patients with persistent pulmonary arterial hypertension survive (3) and are frequently weaned from mechanical ventilation within a few days (4). Treatment of persistent pulmonary arterial hypertension with ECMO assumes that a) pulmonary arterial hypertension will improve over several days after correcting hypoxemia and reducing mean airway pressure (5); and b) after improvement, pulmonary arterial hypertension will not recur. However, in some infants, especially those patients with congenital diaphragmatic hernia, persistent pulmonary arterial hypertension and lung function do not improve despite ECMO therapy (6). These nonresponders account for many of the approximately 20% of all ECMO patients who do not survive (3, 6). Pulmonary artery pressures and echocardiographic findings after ECMO are not well studied, and the return of severe pulmonary arterial hypertension following apparently successful ECMO has not been described. We report life-threatening, recurrent pulmonary arterial hypertension after apparently successful ECMO therapy in three patients, two of whom survived without repeat courses of ECMO therapy.

Lupus anticoagulants in systemic lupus erythematosus: prevalence and clinical associations.

The prevalence of lupus anticoagulant (LAC) and its relation with reported clinical associations has been determined in 55 patients with systemic lupus erythematosus (SLE) from northern India who were studied prospectively. Kaolin clotting time was used to screen for LAC, which was detected in seven (13%) of the patients. Significant associations were found between LAC and thrombotic events, onset of disease at an early age, and disease of shorter duration. No statistically significant association could be found between LAC and recurrent abortions, pulmonary hypertension, thrombocytopenia, and neurological manifestations. It is concluded that LAC is a useful marker for a subset of patients with SLE at risk of thromboembolic events.

Recurrent pulmonary thromboembolism and pulmonary hypertension in rabbits receiving repeated intravenous infusions of autologous thrombus

Recurrent pulmonary thromboembolism and pulmonary hypertension in rabbits receiving repeated intravenous infusions of autologous thrombus