P. Steele

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.

Late cardiopulmonary complication of ventriculo-atrial shunt

A 30-year-old man presented in 1991, with an 18-month history of progressive dyspnoea and cough. His past history included a lumbosacral meningomyelocele. At 7 months of age progressive hydrocephalus was treated by insertion of a ventriculo-atrial (VA) shunt. The meningomyelocele was repaired at 8 months of age. He also had an ileocutaneous ureterostomy, bilateral ileopsoas transplants, and multiple orthopaedic procedures for subluxation of the hips. By the age of 14 years, the VA shunt had been revised on four occasions because of recoil of the distal catheter into the superior vena cava. Two further shunt revisions were done, one for spontaneous disconnection of the proximal catheter and the other for infection. Catheter associated thrombosis was not found on any of the revisions. He had no history of chronic liver disease, deep venous thrombosis, intravenous drug or appetite suppressant use, systemic hypertension, haemoglobinopathies, or other systemic diseases. On examination he had an elevated jugular venous pressure, parasternal heave, a right ventricular gallop rhythm, and an accentuated pulmonary component of the second heart sound. There was no pulsatile liver or evidence of peripheral oedema.

Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?

BackgroundPulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients.MethodsWe performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH) Registry to estimate long-term survival with each therapy.ResultsTen RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD) age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH), 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%.ConclusionWhen applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH therapy.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand

BACKGROUND Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. METHODS Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. RESULTS Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality.

99mTc-imidodiphosphate — A better tracer for infarct-avid imaging

A new radiotracer, 99mTc-imidodiphosphate, has been investigated in a series of 101 consecutive admissions to a Coronary Care Unit in a large teaching hospital to assess its potential as an acute myocardial infarct imaging agent. This agent shows high sensitivity for transmural infarction (0.96), subendocardial infarction (0.88) and high overall specificity (1.00). The clarity of the images produced, and the time after the acute episode when studies were positive suggest that it is the agent of choice for imaging the acutely infarcted myocardium.