Home-made fenestrated amplatzer occluder for atrial septal defect and pulmonary arterial hypertension

We report the management of a patient with secundum atrial septal defect (ASD) and severe pulmonary hypertension. A 65-year-old male with recently diagnosed atrial septal defect was referred to our centre for decompensated right heart failure with rest and exercise induced dispnea and severe pulmonary hypertension. Right heart catheterization confirmed a mean pulmonary pressure of about 55 mmHg and a Qp/Qs of 2.7. An occlusion test with a compliant large balloon demonstrated partial fall of pulmonary arterial pressure. The implantation of a home-made fenestrated Amplatzer ASD Occluder (ASO) was planned in order to decrease left-to-right shunt and promote further decrease of pulmonary arterial pressure in the long-term. Thus, by means of mechanical intracardiac echocardiography study with a 9F 9 MHz UltraIce catheter (Boston Scientific Corp.), we selected a 34 mm ASO for implantation. Four millimeter fenestration was made inflating a 4 mm non-compliant coronary balloon throughout the waist of the ASO, which was successfully implanted under intracardiac echocardiography. After six months, a decrease of pulmonary arterial pressure to 24 mmHg and full compensated right heart failure was observed on transthoracic echocardiography and clinical examination. This case suggests that transcatheter closure with home-made fenestrated ASD in elderly patients with severe pulmonary hypertension is feasible.     

Pulmonary artery thrombi detected by echocardiography in patients with pulmonary hypertension secondary to atrial septal defect.

This report presents three patients with severe pulmonary hypertension secondary to atrial septal defect associated with thrombus and spontaneous echo contrast within the pulmonary artery diagnosed by transthoracic and transoesophageal echocardiography. Clinical and echocardiographic features seem to suggest local thrombus formation within the pulmonary arteries as a direct consequence of pulmonary hypertension rather than venous thromboembolism.     

Assessment and treatment of pulmonary arterial hypertension: an Australian perspective in 2006

Pulmonary arterial hypertension is a group of diseases which forms a small subset of those with elevated pulmonary artery pressure (pulmonary hypertension). The recent development of selective pulmonary vasodilator has lead to a substantial resurgence of interest in what have been previously regarded as rare and incurable diseases. This review aims to describe the spectrum of pulmonary vascular diseases, the evolving understanding as to pathogenesis, the evolving evidence of efficacy for drug therapies, trying to put this into a contemporary Australian context. Several key pathogenic pathways may be involved: prostacycline, Nitric Oxide-cGMP-phosphodiesterase 5 and endothelin- all of which are exploited for therapeutic benefit by newly available drug therapies. A recently modified classification system reasserts the importance of precise diagnosis. The cardinal symptom of exertional dyspnea warrants careful evaluation in an attempt to prevent (frequently occurring) substantial delay in diagnosis. Echocardiogram is the cornerstone of screening for pulmonary arterial hypertension; however, a detailed evaluation including a carefully performed right heart catheterisation with sufficient data to allow calculation of pulmonary vascular resistance is key to accurate diagnosis. These new approaches to therapy are already substantially improving quality of life and prognosis.     

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration

Background Cheyne–Stokes respiration disrupts sleep, leading to daytimesomnolence and cognitive impairment. It is also an independentmarker of increased mortality in heart failure. This study evaluatedthe effectiveness of oxygen therapy for Cheyne–Stokesrespiration in heart failure. Methods Eleven patients with stable heart failure and Cheyne–Stokesbreathing were studied. Oxygen and air were administered for4 weeks in a double-blind, cross-over study. Sleep and disorderedbreathing was assessed by polysomnography. Symptoms were assessedusing the Epworth Sleepiness Scale, visual analogue and qualityof life scores. Cognitive function was assessed by neuro-psychometrictesting. Overnight urinary catecholamine excretion was usedas a measure of sympathetic nerve activity. Results Ninety-seven percent of apnoeas were central in origin. Oxygentherapy reduced the central apnoea rate (18·4±4·1vs 3·8±2·1 per hour;P=0·05) andperiodic breathing time (33·6±7·4 vs 10·7±3·9%of actual sleep time;P=0·003). Oxygen did not improvesleep quality, patient symptoms or cognitive failure. Oxygenreduced urinary noradrenaline excretion (8·3±1·5vs 4·1±0·6nmol.mmol^–1urinary creatinine;P=0·03). Conclusion Oxygen stabilized sleep disordered breathing and reduced sympatheticactivity in patients with heart failure and Cheyne–Stokesrespiration. We were unable to demonstrate an effect on eitherpatient symptoms or cognitive function.     

Living-related lobar transplantation and simultaneous atrial septal defect closure in a young patient with irreversible pulmonary hypertension: a case report

A 6-year-old boy was diagnosed as having atrial septal defect with oversystemic pulmonary hypertension, and gradually developed hypoxia and heart failure. At the age of 11, living-related bilateral lobar lung transplantation from his parents was indicated, because of his critical condition. The estimated forced vital capacity calculated by the donors lower lobes was 104% of his age. The operation was carried out with simultaneous closure of the atrial septal defect under full cardiopulmonary bypass. The postoperative course was complicated with pulmonary edema and phrenic nerve palsy, which were eventually resolved. Six months after surgery he was free from heart failure and rehabilitating at home without oxygen. The final diagnosis was primary pulmonary hypertension with atrial septal defect. Living-related bilateral lobar lung transplantation with simultaneous intracardiac repair may be an optional strategy for children with Eisenmenger syndrome or primary pulmonary hypertension with intracardiac defect when cadaveric transplantation is not possible.     

IVI epoprostenol as salvage therapy in pulmonary arterial hypertension: an Australian perspective

Background: IVI epoprostenol is the only therapy for pulmonary arterial hypertension (PAH) with a randomized controlled trial demonstrating improved survival, when used as first‐line monotherapy. In Australia it is used as salvage therapy for those failing treatment with other targeted therapies or presenting in World Health Organization functional class (FC) IV. Aims: Report experience with IVI epoprostenol, administered as salvage therapy for the treatment of adults with PAH in a single Australian PAH centre. Methods: Retrospective case series of all patients commenced on IVI epoprostenol for PAH, between 2002 and 2010. Review of case notes with collection of data at baseline and after treatment, including FC, 6‐min walk test (6MWT), right ventricular systolic pressure (RVSP) on echocardiogram, patient survival and treatment complications. Change in indices was assessed using the Wilcoxon Sign Rank Test and is expressed as median (inter‐quartile range). Results: A total of 23 patients was included. Treatment was generally well tolerated with few major complications. At the end of the study period, nine patients were successfully bridged to transplant, five had a sustained response to IVI epoprostenol, six had an incomplete response but were clinically stabilized, two died awaiting transplant and one died who was not a candidate for transplantation. Overall, when measured at best level post initiation of IVI epoprostenol, there were significant improvements in FC ?1 [0 to ?1] (P < 0.0001), 6MWT (m) +117 [70–264] (P= 0.002) and RVSP (mmHg) ?7.0 [4.0 to ?45] (P= 0.03). Conclusion: Findings support efficacy of epoprostenol as salvage therapy for patients with PAH.     

Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: a pilot study

Despite the introduction of new drugs that have changed the course of pulmonary arterial hypertension (PAH), some patients are still refractory to treatment and deteriorate rapidly. Long-acting phosphodiesterase-5 inhibitors are a new class of drugs that are effective in PAH. This prospective study assessed the potential of combination therapy with prostacyclin and tadalafil for treatment of severe PAH. We report four cases of severe PAH that deteriorated despite prostacyclin therapy. Two patients had Eisenmenger syndrome, one had pulmonary hypertension associated with scleroderma and one had histiocytosis X. All were treated with tadalafil, 10-20 mg once daily, in addition to prostacyclin. After 3 months of treatment, all patients improved clinically, with an increase in mean 6MWD from 214 to 272 m. In three patients, the New York Heart Association functional class decreased from IV to III. Echocardiograms showed no significant changes in pulmonary arterial pressure. Although this study was limited by the small sample size, it suggests that tadalafil in combination with prostacyclin is an effective treatment for severe PAH. Tadalafil may be beneficial for the treatment of patients with advanced disease.     

Ectopic pancreatic fat as a risk factor for hypertension in children and adolescents with nonalcoholic fatty liver disease

Although nonalcoholic fatty liver disease (NAFLD) is known to be a risk factor for cardiovascular diseases, few studies have reported an association between ectopic fat deposition and metabolic complications, including hypertension, in children with NAFLD. The present study evaluated the risk factors for hypertension in children with NAFLD from the aspect of ectopic fat. This cross‐sectional retrospective study investigated 65 children with NAFLD (49 boys, mean age 13.0 ± 3.2 years, mean body mass index z‐score [BMI‐z] 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging‐based fat fraction measurement for ectopic hepatic and pancreatic fats, as well as anthropometry, blood pressure, laboratory tests, and body composition analysis. A logistic regression model was used to identify the risk factors for hypertension. Through a simple logistic regression analysis, age (OR 1.392), BMI‐z (OR 3.971), waist circumference‐to‐height ratio (OR 1.136), fat‐free mass index (OR 1.444), γ‐glutamyl transferase (OR 1.021), quantitative insulin sensitivity check index (OR 0.743), dyslipidemia (OR 5.357), and pancreatic fat fraction (PFF) (OR 1.205) were associated with hypertension. The optimal cut‐off of PFF to divide children with NAFLD into two groups with and without hypertension was 4.39% (area under the curve 0.754, p = .001, sensitivity 82.4%, specificity 73.9%). Multiple logistic regression analysis in the fully adjusted model revealed both BMI‐z (OR 4.912, 95% CI, 1.463–16.497) and PFF (OR 1.279, 95% CI, 1.007–1.624) were independent risk factors for hypertension. In conclusions, in addition to BMI‐z, ectopic pancreatic fat is an important risk factor for hypertension in children with NAFLD.     

Hemodynamic effects of nifedipine and oxygen in children with pulmonary hypertension

Summary Fourteen patients, 2 to 20 years old were investigated. Two had primary pulmonary hypertension, 11 had congenital heart disease and post-tricuspid shunts, and 1, a 20-year-old patient, was investigated after he had undergone surgical correction of truncus arteriosus I. Pulmonary arterial pressure, pulmonary flow index, peripheral systolic blood pressure and heart rate were measured before, and several times after intrapulmonary injection into the pulmonary artery of 0.5 g nifedipine/kg. Six patients were given an additional dose of 1 g nifedipine per kilogram into the pulmonary artery and hemodynamic measurements were repeated. In eight children, receiving 100% oxygen via a breathing mask, nifedipine effects were compared with oxygen effects. After 10 minutes under oxygen, the same hemodynamics were determined as after nifedipine. In addition, in four of these children aortic pressure and arterial oxygen saturation were also measured. Maximal effects occurred within 4 minutes. 0.5 g nifedipine per kilogram caused a slight reduction in mean pulmonary arterial pressure (p<0.05), as well as increase in pulmonary flow index (p<0.005). However, no significant change in heart rate or in systolic blood pressure was observed. 1 g nifedipine per kilogram IP had almost the same effects. No adverse side effects occurred, besides mild headaches in one child. A comparison of nifedipine injected into the pulmonary artery with oxygen breathing in congenital heart disease combined with pulmonary hypertension, is reported for the first time. Nifedipine had a more pronounced and beneficial effect with a selective action on the pulmonary vascular bed.     

Residual pulmonary vasoreactivity to inhaled nitric oxide in patients with severe obstructive pulmonary hypertension and Eisenmenger syndrome

OBJECTIVE—To determine whether inhaled NO (iNO) can reduce pulmonary vascular resistance in adults with congenital heart disease and obstructive pulmonary hypertension or Eisenmenger syndrome.
DESIGN—23 patients received graded doses of iNO. Pulmonary and systemic haemodynamic variables and circulating cyclic guanosine monophosphate (cGMP) concentrations were measured at baseline and after 20 and 80 ppm iNO. Patients were considered responders when total pulmonary resistance was reduced by at least 20%, and rebound was defined as a greater than 10% increase in total pulmonary resistance upon withdrawal from iNO.
RESULTS—In response to 20 ppm iNO, total pulmonary resistance decreased in four patients (18%, 95% confidence interval (CI), 2% to 34%), while in response to 80 ppm iNO it decreased in six patients (29%, 95% CI 10% to 38%). Systemic blood pressure did not change. Withdrawal resulted in rebound in three patients (16%, 95% CI 0% to 32%) after cessation of 20 ppm iNO, and in six patients (35%, 95% CI 12% to 58%) after cessation of 80 ppm iNO. Patients with predominant right to left shunting did not respond. In all patients cGMP increased from (mean (SD)) 28 (13) µmol/l at baseline to 55 (30) and 78 (44) µmol/l after 20 and 80 ppm iNO (p < 0.05 v baseline).
CONCLUSIONS—NO inhalation is safe and is associated with a dose dependent increase in circulating cGMP concentrations. Pulmonary vasodilatation in response to iNO was observed in 29% of patients and was influenced by baseline pulmonary haemodynamics. Responsiveness to acute iNO may identify patients with advanced obstructive pulmonary hypertension and Eisenmenger syndrome who could benefit from sustained vasodilator treatment.


Keywords: nitric oxide; pulmonary hypertension; Eisenmenger syndrome     

Nebulized therapies for childhood pulmonary hypertension: an in vitro model

OBJECTIVES: Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. DESIGN: Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model. RESULTS: Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles < or = 5 microm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model. CONCLUSIONS: All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug.     

Combined percutaneous pulmonary valvuloplasty and atrial septal defect closure for pulmonary valvular stenosis and associated secundum atrial septal defect in an adult.

Percutaneous balloon valvuloplasty is the treatment of choice for congenital pulmonary valve stenosis, and percutaneous closure of secundum atrial septal defects has become a promising alternative to surgery in selected patients. We report a case of combined percutaneous pulmonary valvuloplasty and secundum atrial septal defect occlusion in an adult patient.     

Prospects for improving outcomes in systemic sclerosis‐related pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Approximately one in 10 will develop PAH during their lifetime. These patients have a worse prognosis than those with PAH due to other causes. The most common clinical feature of SSc‐PAH in the early stages is non‐specific exercise intolerance that can be erroneously attributed to other manifestations of SSc. Screening provides an opportunity for early identification of SSc‐PAH and prompt initiation of therapies with the potential to improve quality of life and survival. International guidelines recommend annual transthoracic Doppler echocardiography (TTE), but TTE has limitations. The tricuspid regurgitant jet required for estimating the systolic pulmonary artery pressure is absent in up to 39% of patients, including a proportion with PAH. This has prompted a move to new screening algorithms that are less dependent on TTE. Not all pulmonary hypertension (PH) in patients with SSc is PAH. Other causes include PH secondary to left heart disease, interstitial lung disease‐related PH, chronic thromboembolic PH and pulmonary veno‐occlusive disease. With the advent of evidence‐based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. The role of anti‐coagulation for SSc‐PAH has been the subject of a recent meta‐analysis of nine observational studies that suggests it may confer a survival benefit, but to date, there have been no randomised controlled trials to confirm this.     

Survival after the initiation of combination therapy in patients with pulmonary arterial hypertension: an Australian collaborative report

Background: Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. Methods: From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II–IV PAH deteriorating on monotherapy received non‐parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6‐min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6‐monthly intervals thereafter. Results: After varying periods of monotherapy (18.7 ± 13.4 months), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3 years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1 year and 79% at 2 years, and for scleroderma‐related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1 ± 0.6 on monotherapy to 2.2 ± 0.6 at 12 months. Similarly, dual therapy improved 6‐min walk distance from 316 ± 119 m to 406 ± 129 m at 12 months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. Conclusions: Dual non‐parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long‐term outcomes.