Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing.

BACKGROUND: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. METHODS: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). RESULTS: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). CONCLUSION: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted.

Retrospective Validation of the REVEAL 2.0 Risk Score With the Australian and New Zealand Pulmonary Hypertension Registry Cohort.

BACKGROUND: Pulmonary arterial hypertension (PAH) prognosis has improved with targeted therapies; however, the long-term outlook remains poor. Objective multiparametric risk assessment is recommended to identify patients at risk of early morbidity and mortality, and for optimization of treatment. The US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk score is a new model proposed for the follow-up of patients with PAH but has not been externally validated. METHODS: The REVEAL 2.0 risk score was applied to a mixed prevalent and incident cohort of patients with PAH (n = 1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier survival was estimated for each REVEAL 2.0 risk score strata and for a simplified three-category (low, intermediate, and high risk) model. Sensitivity analysis was performed on an incident-only cohort. RESULTS: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ Registry cohort, with a C statistic of 0.74 (both for full eight-tier and three-category models). When applied to incident cases only, the C statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12- and 60-month survival estimates (all risk category comparisons P < .001). Although the full eight-tier REVEAL 2.0 model separated patients at low, intermediate, and high risk, survival estimates overlapped within some of the intermediate- and high-risk strata. CONCLUSIONS: The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of patients with PAH at follow-up. The simplified three-category model may be preferred for clinical use and for future comparison with other prognostic models.

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.

Does exercise pulmonary hypertension exist?

PURPOSE OF REVIEW: The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. RECENT FINDINGS: Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. SUMMARY: Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

Exudative bronchiolitis after lung transplantation.

BACKGROUND: After lung transplantation patients frequently develop small airways disease. Exudative bronchiolitis (EB) has not been described previously in this population. We describe a case series of patients who have developed EB after lung transplantation. METHODS: We reviewed the clinical records and radiologic data of 99 patients who underwent single and bilateral lung transplantation. Data relating to ethnicity, transplant indication, human leukocyte antigen (HLA) status, complications and survival were recorded. The EB cohort, defined by high-resolution computed tomographic (HRCT) evidence of the disease, was compared with a group of patients who had not developed EB. RESULTS: The majority of patients had chronic obstructive pulmonary disease (COPD; n = 51), followed by cystic fibrosis (CF; n = 22), pulmonary fibrosis (n = 8), pulmonary hypertension (n = 7), bronchiectasis (n = 5), lymphangioleiomyomatosis (n = 3) and Eisenmenger's syndrome (n = 3). Thirteen patients were found to have developed EB. EB was more commonly seen in Maori and Pacific Island patients (p < 0.05). EB was significantly associated with early infection post-transplant (p < 0.05) and a history of Aspergillus infection (p < 0.005) or diabetes (p < 0.05). The patients with EB were also significantly more likely to develop bronchiolitis obliterans syndrome (p < 0.0005), bronchiectasis (p < 0.0005) or small airways disease (p < 0.05). Patients with EB had a varied response to treatment, with the majority showing improvement. CONCLUSIONS: EB was noted to occur after lung transplantation in a significant proportion of patients, but will not be detected unless HRCT is used routinely. It has been associated with patients' ethnicity, donor haplotype, infection and the development of airways disease. EB may be a prominent indicator of the likelihood of developing BOS.

Diving-related pulmonary oedema as an unusual presentation of alcoholic cardiomyopathy.

Diving-related pulmonary oedema (DRPO) is an uncommon and incompletely understood phenomenon. Pulmonary oedema has been rarely documented in shallow water. It is also associated with cold water and exertion and has been seen in swimmers as well as divers with no underlying heart disease. We describe an otherwise well 69-year-old lady who developed diving-related pulmonary oedema on her second and third dives in a shallow, heated pool. Follow-up echocardiogram revealed moderate global left ventricular dysfunction with an ejection fraction of 37%. There was a history of alcohol consumption of half a bottle of wine per day, which combined with the echocardiographic findings led to the diagnosis of alcoholic cardiomyopathy. We believe this not only to be the oldest patient with a documented case of DRPO but also the first report where it has clearly unmasked clinically significant underlying heart disease.

A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea.

STUDY OBJECTIVES: To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces. DESIGN: A randomized single-blind crossover study. SETTING: Hospital-based sleep laboratory. PATIENTS OR PARTICIPANTS: 21 CPAP-naïve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) INTERVENTIONS: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05). CONCLUSIONS: This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated.

Home overnight pulse oximetry in patients with COPD: more than one recording may be needed.

STUDY OBJECTIVES: Home overnight pulse oximetry (OPO) is used to assess nocturnal desaturation in patients with COPD, but the current practice of relying on one recording has not been studied. We assessed the variability of nocturnal desaturation in patients with COPD between nights, as measured by home OPO. DESIGN: Study subjects attended for clinical evaluation, spirometry, and arterial blood gas analysis. OPO was prospectively completed at home on 2 consecutive nights (study night 1 [N1] and study night 2 [N2]) and repeated at 3 weeks (study night 3 [N3]). SETTING: Respiratory Services, Green Lane Hospital, Auckland, New Zealand. PATIENTS: Twenty-six patients with clinically stable COPD (mean age, 69.3 years [SD, 6.9]; FEV(1), 28.6% predicted [SD, 10.6]; PO(2), 71.3 mm Hg [SD, 9.8]). Patients with asthma or clinical evidence of obstructive sleep apnea were excluded. MEASUREMENTS AND RESULTS: Mean nocturnal saturation (MNS) and time spent with saturation below 90% (TB90%) were calculated for N1, N2, and N3. Group mean recording length, MNS, and TB90% were similar for each night. Little variation in MNS was seen between nights (N1 and N2 mean difference, 1.31%; N2 and N3, 1.26%; N1 and N3, 1.25%). Larger variation was seen between nights for TB90% (N1 and N2 mean difference, 17.46%; N2 and N3, 9.95%; N1 and N3, 14.05%). No factors were identified that predicted increased variability of TB90%. Using the current definition of "significant nocturnal desaturation" (TB90% > or = 30% of the night), 9 of 26 patients (34.6%) changed category between "desaturator" and "nondesaturator" from N1 to N2. CONCLUSION: Nocturnal desaturation in patients with COPD exhibits considerable night-to-night variability when measured by home OPO. A single home OPO recording may be insufficient for accurate assessment of nocturnal desaturation.