Abstract
G Strange,1 M Rose,2 F Kermeen,3 A Keogh,4 L Grigg,5 C O'Donnell,6 R Weintraub,2 D Celermajer1
1Royal Prince Alfred Hospital, Sydney Australia; 2Royal Children's Hospital, Melbourne, Australia;3Prince Charles Hospital, Brisbane, Australia; 4St. Vincent's Hospital, Sydney, Australia; 5Royal Melbourne Hospital, Melbourne, Australia; 6Auckland City Hospital, Auckland, New Zealand
Address correspondence to Dr. Geoff Strange, Pulmonary Hypertension Society ANZ, Inc., PO Box 133, Sans Souci, New South Wales 2219, Australia. E-mail:
There are now more adults (>16 years) than children with congenital heart disease (CHD) in Australasia. Previous data suggest that up to 5% may have pulmonary hypertension (PAH). However, registry data are lacking: the prevalence, characteristics, treatment patterns, and outcomes are not well characterized. We therefore established a binational registry to address some of these questions. A comprehensive database was developed. After appropriate ethics approvals were obtained, subjects from all the major adult CHD units in Australia and New Zealand were identified. Patients were included if they had been seen at least once after January 1, 2000, with an established diagnosis of PAH complicating CHD. Three-hundred sixty patients have been entered into the registry. Sixty percent of the patients were female and 85% Caucasian. Patients had their first diagnosis of CHD at 7.94 ± 15.01 years. Age at first visit to the ACHD center was 31.2 ± 13.99 years. Patients recognized their first symptom at age 24.6 ± 16.45 years, exposing a 6.48 ± 8.91-year interval between symptom recognition and adult-center diagnosis of PAH. Dyspnea was the primary presenting symptom in 85% of patients. Diagnosis was based on right heart study in 58% of patients and on echo only in 32%, with 2% based on clinical findings alone. Sixty-four percent and 65% of patients, respectively, had established RVH and dilation on echocardiogram. Underlying CHD diagnoses in these subjects were ASD (21%), PDA (15%), VSD (34%), AVSD (14%), and the remaining, complex lesions (18%). Thirty-four percent of patients underwent surgical repair, 68% had Eisenmenger syndrome, and 24% had Down syndrome. Functional class (FC) at first ACHD center visit was FC III in 56% of cases and FC II in 34%. Mean 6MWT was 364 m at baseline diagnosis. Survival estimates were 88%, 79%, and 69%, respectively, at 5, 10, and 15 years of follow-up. Baseline walk test had a significant impact on survival. The ANZ PAH-CHD database is one of the largest international registries addressing this question. Substantial delays in adult diagnosis exist. Significant collaboration is warranted to address this delay in presentation, which may impact long-term outcomes.
A Keogh,1 RN Channick,2 N Galiè,3 L Perchenet,4 LJ Rubin,5 G Simonneau6
1St. Vincent's Hospital, Darlinghurst, Sydney, Australia; 2Massachusetts General Hospital, Boston, Massachusetts, USA;3University of Bologna, Bologna, Italy; 4Actelion Pharmaceuticals, Allschwil, Switzerland; 5University of California San Diego, LaJolla, California, USA; 6Hôpital Universitaire de Bicêtre, Université Paris-Sud, Le Kremlin Bicêtre, France
Macitentan, a novel dual endothelin receptor antagonist, significantly reduced the risk of morbidity and mortality (primary end point) in PAH in the SERAPHIN study (NCT00660179). A significant reduction in hospitalization for PAH and death due to PAH (secondary end point) versus placebo was also achieved with macitentan (3 mg: 33%, P = 0.0146; 10 mg: 50%, P < 0.0001). The effect of macitentan on other hospitalization-related end points is reported. Patients (≥12 years) with PAH in WHO functional class (FC) II–IV were randomized to oral macitentan 3 mg (n = 250), macitentan 10 mg (n = 242), or placebo (n = 250) once daily in this double-blind outcomes trial. Time to PAH-related hospitalization up to end of treatment was evaluated via Kaplan-Meier analysis. Annual rates of PAH-related hospitalizations and inpatient hospital-days up to end of treatment were analyzed (adjusted for baseline WHO FC and 6-minute walk distance). Overall, 33%, 23%, and 20% of placebo, macitentan 3 mg, and macitentan 10 mg patients, respectively, were hospitalized at least once for PAH. Reductions in risk of PAH-related hospitalization (3 mg: 39%, P = 0.0040; 10 mg: 50%, P = 0.0001), annual rates of hospitalization (3 mg: 43%, P = 0.0068; 10 mg: 55%, P = 0.0002), and inpatient hospital days (3 mg: 33%, P = 0.2707; 10 mg: 52%, P = 0.0416) with macitentan are shown. Macitentan significantly reduced the risk of hospitalization for PAH and the number of PAH-related hospitalizations and inpatient days (10 mg only) per year. These data provide further evidence that macitentan beneficially impacts long-term PAH-related outcomes.
J Lee,1 T Williams,2 T Miller,2 C Manterfield,2 H Whitford,2 P Myles,2 E Paul,2 D Garner3
1Monash Medical Centre, Melbourne, Australia; 2Alfred Hospital, Melbourne, Australia; 3Royal Melbourne Hospital, Melbourne, Australia
Our objectives were to describe the point prevalence of diastolic dysfunction (LVDD) and associated pulmonary hypertension (PHT) in an Australian population of older adults undergoing elective surgery and to assess consequences on symptoms, functional class, and morbidity. The study was a retrospective analysis of transthoracic echocardiograms of patients over the age of 60 seen in the preadmission clinic in a tertiary hospital over a 12-month period. Ninety-six patients without known significant cardiopulmonary disease were included. Eighty-seven percent of the 77 patients with measurable diastolic parameters had echocardiographic evidence of LVDD. The right ventricular systolic pressure (RVSP) was able to be estimated in 71 patients and averaged 39 mmHg, (borderline pulmonary hypertension range), with 12% of patients having an elevated RVSP above 50 mmHg (moderate or severe). Patients with an RVSP greater than 40 mmHg were more likely to experience subjective dyspnea (66.7% vs. 16.9%, P = 0.0014) and to have a higher WHO functional class (functional class II vs. I; P < 0.001) but did not have significantly prolonged hospital stays (P = 0.61). Diastolic dysfunction, identified using echocardiographic criteria, was seen in the majority of over-60-year-olds without overt cardiorespiratory disease in this study. It was also frequently associated with pulmonary hypertension. Patients with both LVDD and PHT tend to be symptomatic and have a more limited functional class. Population-based studies would appear to be the next step to help to more precisely define prevalence, but more importantly to determine the natural history of asymptomatic LVDD in the older person.
P Choudhary, E Lau, L Simmons, T Corte, D Celermajer
Royal Prince Alfred Hospital, Sydney, Australia
Our aim was to investigate the role of dobutamine stress echocardiography for noninvasive detailed physiological assessment of the pulmonary circulation. Stress testing of the pulmonary circulation (via increasing pulmonary blood flow) enables determination of multipoint mean pulmonary artery pressure–cardiac output (mPpa-Q) relationships. Dobutamine-induced mPpa-Q relationships could provide additional pathophysiologic insights allowing early identification of pulmonary vascular disease. Thirty-eight subjects (pulmonary arterial hypertension [PAH]: n = 16, age 56 ± 9 years; and healthy controls: n = 22, age 46 ± 16 years) underwent dobutamine stress echocardiography using an incremental dose protocol (up to 20 μg/kg/min). Another healthy control group (n = 22, age 44 ± 13 years) underwent exercise echocardiography at progressive workloads. Multipoint mPpa-Q plots were analyzed, and the pulmonary vascular distensibility coefficient α was calculated. Dobutamine stress echocardiography was feasible and informative in 93% of subjects. The average dobutamine-induced mPpa-Q slope was 1.1 ± 0.7 mmHg/L/min in healthy controls and 5.1 ± 2.5 mmHg/L/min in PAH patients (P < 0.001). Dobutamine-induced α was markedly reduced in PAH patients (0.003 ± 0.001/mmHg vs. 0.02 ± 0.01/mmHg in controls, P < 0.001). When exercise and dobutamine stress were compared in healthy controls, exercise-induced mPpa-Q slope was modestly higher (2.2 ± 1.7 mmHg/L/min, P = 0.008 vs. dobutamine). In PAH patients, NYHA functional class status was associated with dobutamine-induced mPpa-Q slopes (P = 0.013) but not with resting total pulmonary vascular resistance. In conclusion, noninvasive assessment of pulmonary mPpa-Q relationships is feasible with dobutamine stress, with marked differences shown between controls and PAH patients. Dobutamine stress echocardiography may potentially be a valuable noninvasive technique for stress testing of the pulmonary vasculature.
W Lau,1 N Dywer,2 D Abelson,1 M Ng,1 D Celermajer1
1Royal Prince Alfred Hospital, Sydney, Australia; 2Royal Hobart Hospital, Hobart, Australia
The assessment of right ventricular afterload is of fundamental importance in pulmonary arterial hypertension (PAH). We present a time domain approach using wave intensity analysis (WIA) to describe ventriculoarterial interactions of the pulmonary circulation. High-fidelity pressure and Doppler flow velocity measurements were made in the pulmonary arteries (PA) in 6 PAH patients and 7 controls. WIA was applied to determine wave speed and to quantify wave energy for the separate forward- and backward-traveling waves. Three consistent waves were present in both PAH patients and controls: (1) an early-systolic forward compression wave (FCW); (2) a late-systolic forward expansion wave (FEW); and (3) a mid-late-systolic backward (reflected) compression wave (BCW). In PAH patients, the most striking difference was a ~5-fold increase in total BCW intensity ([56.9 ± 14.6] × 102 vs. [10.7 ± 5.6] × 102 W m−2 s−1, P < 0.01) compared to controls, originating from a 15 ± 5-cm downstream reflection site. Furthermore, the BCW arrived earlier following the incident FCW in PAH patients (45 ± 20 vs. 89 ± 30 ms, P < 0.05), explained by their higher wave speed (6.9 ± 1.3 vs. 3.8 ± 1.0 m s−1, P < 0.01). Wave speed correlated significantly with PA capacitance (r = 0.7, P = 0.005). Total FCW and FEW intensities were also higher in PAH patients ([164.5 ± 39.7] × 102 vs. [88.3 ± 20.7] × 102 W m−2 s−1, P < 0.01, and [85.1 ± 36.0] × 102 vs. [32.5 ± 13.7] × 102 W m−2 s−1, P < 0.01, respectively). We found distinct alterations in wave travel in patients with PAH, characterized by markedly enhanced early arrival of BCWs originating from distal microcirculatory reflection sites. WIA allows description of pulsatile wave events in a time domain-based model of pulmonary hemodynamics.
N Morris,1 H Seale,2 B Johnson,3 F Kermeen2
1Griffith University, Gold Coast Campus, Southport, Australia; 2Prince Charles Hospital, Brisbane, Australia; 3Mayo Clinic, Rochester, Minnesota, USA
In pulmonary hypertension (PH), the 6-minute walk distance (6MWD) differentiates patients based on WHO Functional Class (FC); however, its relationship to other indices of disease severity, such as pulmonary artery pressure (PAP) and vascular resistance (PVR), is unclear. There is evidence that indices of gas exchange obtained during exercise, such as breathing efficiency (BE: VE/VECO2) and end-tidal CO2 (PETCO2) relate to disease severity; hence, the purpose of this study was to examine the relationship between disease severity and gas exchange measures made during a 6MWT. Fifty patients (49 ± 17 years, FC = 2.2 ± 0.5) completed a 6MWT while gas exchange was measured simultaneously. End-exercise 6MWD, BE, PETCO2, and a noninvasive gas exchange estimate of pulmonary vascular capacitance (PCAP = oxygen pulse × PETCO2) were correlated with resting echocardiography measures of RV systolic pressure (RVSP). In a subgroup (n = 15, FC = 2.3 ± 0.5, category 1 PH), resting right heart catheterizations (RHC) were performed, and PAP and PVR were determined. The mean 6MWD was 504 ± 102 m. There was no relationship between 6MWD and RVSP (70 ± 23 mmHg, r = −0.15, P = 0.51); however, end-exercise BE (42 ± 10, r = 0.63), PETCO2 (27.2 ± 7.1 mmHg, r = −0.60), and PCAP (204 ± 107, r = −0.47) were significantly (P < 0.01) related to RVSP. In the subgroup of RHC patients, only end-exercise PETCO2 (25.7 ± 5.8 mmHg) and PCAP (186 ± 94) were significantly correlated with PVR (PETCO2: r = −0.46, PCAP: r = −0.56) and PAP (PETCO2: r = −0.44, PCAP: r = −0.56). We conclude that noninvasive gas exchange measures may be a useful addition to the 6MWD and provide a more sensitive method for PH screening and tracking response to therapy.
D Seaton,1 B Shearer,1 K Aldridge,1 J Chan,2 A Yamada,2 F Kermeen2
1Queensland Nuclear Imaging, Brisbane, Australia; 2Prince Charles Hospital, Brisbane, Australia
Identifying accurate and reliable echocardiographic parameters for the functional assessment of the right ventricle (RV) in pulmonary hypertension (PHT) remains a challenge. Speckle-tracking echocardiography allows angle-independent evaluation of myocardial strain, does not rely on geometric assumptions, and may provide reliable measurements in patients with PHT. Our aim was to test the utility of RV speckle-tracking strain analysis compared with conventional echocardiographic parameters and with pulmonary hemodynamics, 6MWT, and DLCO.
Fifty-one (72% F) patients from a tertiary PAH center—20 IPAH, 1 FPAH, 6 PAH-CHD, 12 PAH-CVD, 5 CTEPH, 1 portopulmonary, and 6 out-of-proportion PHT—underwent RV protocol strain analysis (EchoPac 2D speckle) over 3/12. Mean age was 56.6 ± 17.7 years, mean NYHA-FC was 2.9 ± 0.6, and mean 6MWT was 414 ± 150.3 m, with 57% of patients prescribed mono, 29% dual, and 14% triple PAH therapies. Echocardiography and RHC confirmed PHT, with mRVSP 85.5 ± 24 mmHg, mRA size 25.4 ± 7.6 cm2, 29% pericardial effusion, TAPSE 18.9 ± 2.3 mm, mPAP 49.4 mmHg, PVR 9.4 WU, and CI 2.3 L/min/m2, compared to mean global strain of −18.2% (range −9.3% to −30%) and mean RV free-wall strain of −19.6% (–11.4% to −25%). Multivariate analysis of the IPAH group showed significant correlation of RV global strain with the percent predicted on 6MWT (r = −0.56, P = 0.006). We conclude that RV strain is a significant predictor of RV dysfunction and correlates with the visual pattern of the “rocking RV” (associated with normal TAPSE, S′) and clinical parameters such as the 6MWT. More research is required to assess the utility of RV strain serial measurements in response to prescription of PAH therapies.
F Kermeen, K O'Brien, P Ve, P Hopkins
Prince Charles Hospital, Brisbane, Australia
Despite improved survival with advanced pulmonary arterial hypertension (PAH) therapies, morbidity and symptom burden related to PAH and its treatment remain significant issues. Our aim was to evaluate end-of-life (EOL) care and referral practices to palliative care from a tertiary PAH center. We conducted a retrospective review of 115 deaths (62% female) from 2004 to 2012 among 427 patients, 43% with PAH-collagen vascular disease, 21% with idiopathic PAH, 10% with PAH-congenital heart disease, and 26% with other PAH. Mean age of death was 63.5 ± 14 years, mean WHO FC was 3.3 ± 0.8, and mean duration of PAH therapy was 33 ± 24 months, with 56% receiving mono, 29% dual, and 15% triple therapies, including IV epoprostenol. Seventy-five percent died from progressive PAH, 12% died from non-PAH-related causes, 8% had a sudden death, and 5% died from PAH crisis. Of the 37% who chose to die at a PAH center, half lived outside the hospital district (OHD), defined as beyond a 100-km radius. Thirty-three percent (2/3 OHD) chose to die at home and 28% (2/3 OHD) at another hospital, and 2% were admitted to a hospice. Sixty-six percent of patients referred to community palliative care chose to die either at a PAH center or at home. Patients with collagen vascular disease are overrepresented in deaths from PAH. Despite geographical barriers and referral to palliative care, a significant percentage of patients chose EOL care at a PAH referral center. Caring physicians and health professionals of PAH require skills in palliative care as part of their core competencies.
P Moodie,1 K Whyte,2 L Beckert,3 A Aitken,4 C O'Donnell,2 H Wilson, N Ninow1
1Pharmaceutical Management Agency (PHARMAC), Wellington, New Zealand; 2Auckland City Hospital, Auckland, New Zealand;3Christchurch Hospital, Christchurch, New Zealand; 4Wellington Hospital, Wellington, New Zealand
In July 2009, the New Zealand government's medicines-funding agency, PHARMAC, established criteria for access to pulmonary vasodilator therapy via a panel of clinicians. Combination therapy is funded if there is convincing evidence of deterioration. We report the outcome of decisions made by the PAH panel between July 2009 and December 2012 (41 months). Three hundred eighty-three initial applications led to 308 approvals (80%), 6 withdrawals, and 68 declines (18%). Of 265 patients starting treatment since July 2009, 163 (62%, 37.1 per million population) continued to receive PAH medication by December 2012, with most ex-recipients having died or undergone transplantation. Overall survival data were influenced by patients who had initiated therapy prior to the panel being established: in effect, “prevalent” rather than “incident” patients. Seventy approvals were for patients under 10 years of age. Indications were predominately congenital/persistent pulmonary hypertension of the newborn (n = 47) or to improve a Fontan circulation (n = 10); 6 children had idiopathic PAH. Twelve patients with Eisenmenger physiology were approved for vasodilator therapy. Use of combination therapy has not increased appreciably and currently comprises 28% of patients. For adult patients with group 1 PAH, the proportion receiving combination therapy is 24%–30% overall. In conclusion: (1) management via a special panel seemly reduces the inappropriate use of pulmonary vasodilator therapy; (2) we have observed a significant and unforeseen demand for these therapies in neonates and infants; and (3) decision by a panel may be a cost-effective way to provide appropriate access, including combination therapy.
Seale,1 N Morris,2 J Harris,1 K Hall,1 F Kermeen1
1Prince Charles Hospital, Brisbane, Australia; 2Griffith University, Gold Coast Campus, Southport, Australia
CHD-associated PAH is characterized by exercise intolerance, fatigue, and significant oxygen desaturation and is related to morbidity and mortality. The study aimed to characterize the cardiopulmonary exercise responses to the 6MWT and the relationship to disease severity. We hypothesized that the degree of desaturation would be related to end-exercise gas exchange measurements of breathing efficiency (BE) and PETCO2. Prospectively, 19 patients (16 F, 41 ± 14.3 years) completed a 6MWT while gas exchange was simultaneously measured. Pre- and end-exercise measurements of VO2, VCO2, VE, and BE were determined from 30-second averages. Heart rate (HR), SpO2, and breathlessness were recorded every minute. All patients underwent echocardiography, with standard measurements of right ventricular (RV) function. Data are presented as mean ± SD. Mean 6MWD was 467.2 ± 115 m, WHO functional class was 2.3 ± 0.5, FEV1 was 75.1% ± 14.9%, DLCO was 66.0% ± 18%, RVSP was 86.4 ± 20.7 mmHg, and TAPSE was 15.7 ± 4.4 mm. During 6MWT, significant (P < 0.001) increases in VO2 (pre: 5.9 ± 1.2, end: 12.1 ± 3.3 mL kg−1 minute−1), VE (pre: 17.3 ± 5.4, end: 39.9 ± 112.4 L minute−1), HR (pre: 84 ± 13, end: 174 ± 12 beats minute−1), and breathlessness (pre: 0.4 ± 0.8, end: 3.6 ± 1.6) and a significant (P < 0.001) fall in SaO2 (pre: 91.1% ± 5.8%, end: 73.5% ± 14.8%) were observed. No significant change in BE (pre: 43.3 ± 7.1, end: 44.9 ± 10.1). The fall in SaO2 was significantly related to the end-exercise VEVCO2 (r = 0.63, P < 0.01) and PETCO2 (r = 0.58 P < 0.01). This study demonstrates that breathing efficiency and PETCO2 correlate to degree of desaturation and contribute to mechanisms of exercise intolerance in CHD-associated PAH.
J Cham, D Boshell, D Boyd, A Keogh, E Kotlyar
St. Vincent's Hospital, Sydney, Australia
Pulmonary endarterectomy (PEA) represents a curative therapeutic option for patients with surgically amenable chronic thromboembolic pulmonary hypertension (CTEPH). This retrospective study evaluates PEAs conducted at St. Vincent's Hospital, Sydney, Australia. Eighteen consecutive CTEPH patients (mean age: 68 ± 9 years) underwent PEA between November 2010 and September 2013. PEA involved median sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest (DHCA at 20°C) to enable complete endarterectomy. Two patients with pulmonary angiosarcoma were excluded. Patients were New York Heart Association (NYHA) classes II (n = 2), III (n = 11), or IV (n = 4) preoperatively. Follow-up was at 3, 6, and 12 months. Pulmonary vascular resistance improved immediately postoperatively, from 889 ± 362 to 332 ± 81 dynes/s/cm5 (P = 0.00001). Mean pulmonary arterial pressure fell from 50.6 ± 11.9 to 31.0 ± 4.1 mmHg (P = 0.0000002). Cardiac index improved from 2.1 ± 0.5 to 2.6 ± 0.5 L/min/m2 (P = 0.005). Six-minute-walk test scores increased from 297 ± 124 m preoperatively to 418 ± 55 m at 6 months post-PEA (P = 0.009) and 428 ± 64 m at 12 months post-PEA (P = 0.004). One mortality (5.6%) resulted from persistent pulmonary hypertension in a patient with preoperative decompensated right heart failure, in whom PEA was performed as a salvage procedure. At last follow-up, patients were NYHA classes I (n = 5), II (n = 10), or III (n = 1), with 2 patients awaiting 3-month follow-up. Mean bypass time was 333 ± 86 minutes, and mean DHCA time was 48 ± 17 minutes. We conclude that in CTEPH patients with surgically accessible disease, PEA leads to immediate reduction in pulmonary pressures followed by significant improvements in exercise capacity and quality of life.
P Ve, K O'Brien, N Brar, F Kermeen
Prince Charles Hospital, Brisbane, Australia
Despite intravenous (IV) epoprostenol improving survival and exercise capacity, health professionals have limited knowledge about the lifestyle changes and psychosocial burden facing patients diagnosed with pulmonary arterial hypertension (PAH). Our aim was to investigate and understand the physical, social, emotional, and practical burdens of delivering IV epoprostenol to improve the provision of complex medical therapies and quality of life in PAH patients. A quantitative survey using open-ended questions, pictorial representations, and the disease-specific Cambridge Pulmonary Hypertension Outcome Review (Camphor) was distributed to patients from a tertiary PAH center in Queensland. Seventy percent of patients responded (16 female, 4 male; 2 were excluded), with 14% aged 16–40 years, 65% 40–60 years, and 21% >60 years on triple PAH therapy for a mean of 26 months. More than half of all participants reported that CADD pumps were excessively heavy and annoying to carry and interfered with work, housework, showering, dressings, caring for children, recreational activities, and being intimate with their partners. Social stigma was highly experienced in all participants, leading to social isolation, frustration, and uncertainty. Participants aged 40–60 years reported more technical problems with the pump, particularly dealing with alarms, removing air from lines, and priming the cassette. Data compiled from the Camphor questionnaire remain to be presented. Our data suggest that health professionals underappreciate the significant practical and psychosocial burden of patients living with a diagnosis of PAH and requiring advanced therapies. Furthermore, greater resources are required to explore and improve delivery systems of IV epoprostenol.
M Lysenkov, T Martynuk, V Sergienko, I Chazova
Russian Cardiology Research and Production Complex, Moscow, Russia
Pulmonary arterial hypertension (PAH) is a devastating lung vascular disease. Despite advances in the diagnosis of this condition, early detection and ascertainment of the genesis of pulmonary hypertension are still a difficult task. We supposed that the method of a single-photon emission computed tomography–computed tomography (SPECT/CT) imaging facility is a good alternative in the diagnosis of the genesis of pulmonary hypertension, especially in the early period of the disease and in patients with complex differential diagnosis. We examined 10 people with suspected pulmonary hypertension. Previously, patients underwent right heart catheterization and CT angiography. Three patients' diagnoses of pulmonary hypertension were not confirmed; in 4 cases idiopathic pulmonary hypertension was suspected and in 3 cases pulmonary embolism. After that, the 7 patients with pulmonary hypertension underwent SPECT/CT with intravenous injection of the radiopharmaceutical 99Tc-MAA (macroaggregates of albumin). Because of the capabilities of SPECT/CT to assess perfusion at the level of subsegmental pulmonary arteries, a diagnosis of pulmonary embolism was additionally established in 2 patients from the group with idiopathic pulmonary hypertension. In the other cases, the diagnoses were correct. In our data, we established that the use of SPECT/CT has helped us to establish the correct diagnosis that allows us to assign proper and timely treatment. So we confirmed our hypothesis that the modern method of diagnosis of pulmonary hypertension—SPECT/CT—is no less accurate than the standard methods and is probably preferable in difficult diagnostic cases.
P Ve, K O'Brien, N Brar, F Kermeen
Prince Charles Hospital, Brisbane, Australia
Continuous intravenous epoprostenol improves pulmonary arterial hypertension (PAH) patients' exercise capacity, quality of life, and long-term survival but requires intensive education in the safe and compliant administration of prostacyclin and CADD pumps on a continual basis. Our aim was to evaluate PAH patient's satisfaction with educational material delivered during the institution of IV epoprostenol from a tertiary PAH center in Queensland. Ninety-five percent of patients responded, with 31% aged 16–40 years, 46% 40–60 years, and 23% >60 years. Average time of triple PAH therapies was 17.6 months. Carers are responsible for preparation of drug in 25% of patients 16–40 years old, 16% of those 40–60 years old, and 33% of those >60 years old. Only 75% of patients aged 16–40 years were satisfied with the education booklet, and 75% of those aged 16–40 years and 50% of those aged 40–60 years asked that educational material be available on either USB, a video clip on YouTube, or an app on iPhone or iPad. All age groups asked for more information on Hickman line infections. In conclusion, PAH patients are generally satisfied with current educational material, but the younger cohort requested materials to be provided through social media, including the development of apps to phones and tablets.
M Waugh, P Ve, K O'Brien, M-E Bilby, F Kermeen
Prince Charles Hospital, Brisbane, Australia
Patient support groups provide significant support, which can complement contemporary medical care. A patient pulmonary hypertension (PHT) support group and a follow-up newsletter were established in 2009 by a dedicated social worker with experience in PHT. Review of the literature suggests that little is known about how often these services are actually used in clinical practice or the factors that influence participation. Our aim was to evaluate patients' perceptions and the belief systems of the patient support group and newsletter. We undertook a quantitative survey of 200 patients who attended tertiary PHT service in Queensland. Seventy-nine (39.5%) of the 200 questionnaires were returned. Eighteen patients (22%), aged 17–67 years, and their carers who lived in metropolitan Brisbane attended the support group regularly and reported personal gains of empathy, emotional information, experiential knowledge, and practical information. Overall, 60% of respondents reported that distance was the major barrier to attendance and asked for regional support groups. Eighty-seven percent found the newsletter most beneficial and advocated for more frequent and continued publication. In conclusion, distance is a major barrier for PHT patients to attend a support group in Queensland, but those who attended found the group beneficial. The newsletter provided a much-needed gap to regional patients. PHT patient associations are very much in their infancy in Australia.
D Keating, T Williams, T Miller, C Manterfield
Alfred Hospital, Melbourne, Australia
This case describes the presentation of profound hypoxia and consolidation in a previously asymptomatic 15-year-old female. The first episode was in a peripheral hospital, where persistent desaturation (50%) resulted in ventilation; however, lack of improvement prompted initiation of VV ECMO. A CT angiogram confirmed the presence of a large right-sided AVM. The patient was successfully weaned over 3 days, was discharged, and returned to school. In outpatient care 3 months later, she had oxygen saturations documented at 89% on room air, and an echocardiogram revealed elevated PA pressures, reduced RV function, and hypertrophy. A subsequent virus caused a significant step-down in her clinical status, whereby she required initiation of nitric oxide, but she arrested during intubation and was commenced on VA ECMO. Pulmonary angiography showed minimal blood flow to the left lung and a large AVM in the right lower lobe. Occlusion of the AVM with an angiography balloon resulted in amplification of the PVR (from 22 to 43 WU) and a diminished cardiac index (from 1.6 to 1.3), making radiological coiling unsafe. Additionally, a bronchoscopy was performed and demonstrated a poorly perfused right lung. She was listed for transplantation and was successfully bridged with VA ECMO to lobar transplantation 2 weeks later. Genetic testing showed no mutations (endogen/ELC2) associated with hereditary hemorrhagic telangiectasia. This case illustrates the link between AVM formation and the development of pulmonary arterial hypertension as a result of high-cardiac-output states. In addition, we show the feasibility of ECMO to successfully bridge patients to lung transplantation in highly selected cases.
L Williams,1 B Thomson,1 F Kermeen,2 D Dallimore,3 M Ziegenfuss,4 T Bull,4 D Mullany,4 J Fraser4
1Department of Cardiothoracic Services, Prince Charles Hospital, Brisbane, Australia; 2Queensland Lung Transplant Service, Prince Charles Hospital, Brisbane, Australia; 3Department of Anaesthesia, Prince Charles Hospital, Brisbane, Australia; 4Adult Intensive Care Services, Prince Charles Hospital, Brisbane, Australia
ECMO has been described as perioperative support to facilitate high-risk surgery. Combined pulmonary endarterectomy (PEA), mitral valve replacement (MVR), and myomectomy has not been reported in the literature. Our aim was to describe a patient with severe pulmonary hypertension (PHT) secondary to left ventricular outflow obstruction on background of hypertrophic cardiomyopathy (HOCM), mitral regurgitation (MR), and chronic thromboembolic pulmonary disease (CTEPH), successfully treated with bridging VA-ECMO to PEA, mechanical MVR, and septal myomectomy. A 35-year-old man presented with HOCM (peak LVOT gradient: 98 mmHg, moderate MR, grade II diastolic dysfunction, RV dysfunction, RVSP: 73 mmHg), chronic renal failure (creatinine: 380 mm/L), moderate airflow limitation, obesity (BMI: 34 kg/m2), and OSA. RHC mPAP was 49 mmHg, mRAP was 18 mmHg, LVEDP was 40 mmHg, TPG was 9 mm, PVR was 1.2 WU, and CI was 2.7 L/min/m2. Pulmonary angiogram multiple segmental pulmonary defects consistent with CTEPH out of proportion to PVR. The patient deteriorated preoperatively, with worsening gas exchange and infiltrates on CXR. The combination of pathologies severely limited medical therapeutic options, and the decision was made to commence central VA ECMO to bridge to surgery. Severe pulmonary reperfusion injury and biventricular failure occurred post-PEA, mechanical MVR (31 mm ATS), and septal myomectomy, and central VA ECMO was reestablished and transitioned to VV ECMO 5 days later. Total ECMO duration was 25 days, mechanical ventilation duration was 53 days, and the patient was discharged to rehabilitation on day 63. This case highlights the importance of a multidisciplinary approach and the possibility of bridging patients with reversible life-threatening PHT to surgery using ECMO.
M FitzPatrick,1 CE Wright,2 JE Bourke1
1Lung Health Research Centre, University of Melbourne, Parkville, Victoria, Australia.;2Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia
Intrapulmonary arteries and airways represent an important therapeutic target in many lung diseases, such as pulmonary hypertension and asthma. The development of a novel lung-slice technique, in which changes in artery and airway areas can be visualized simultaneously in situ, provides a potential platform for the assessment of responsiveness to contractile agents and investigation of novel therapies. Since endothelin-1 (Et-1) is a potent vaso- and bronchoconstrictor implicated in disease, our aim was to compare its pharmacology in intrapulmonary arteries and airways. Male Sprague-Dawley rats (250–300 g) were used for preparation of lung slices. Briefly, gelatin (4% in HBSS/HEPES) was injected into the right ventricle, followed by agarose (2% in HBSS/HEPES) into the trachea via cannula, with both gels allowed to set at 4°C. Slices (150-μm thickness) were cut using a vibratome and incubated overnight at 37°C. Changes in artery and airway areas were imaged via phase-contrast microscopy during perfusion with Et-1 in the absence and presence of the nonselective Et-1 antagonist bosentan. Both small arteries and airways (~200–300-μm diameter) contracted in response to Et-1, with maximum reductions in lumen area of ~70% and pEC50 values of 7.7 ± 0.2 and 7.9 ± 0.4, respectively. Comparable contraction was observed in response to serotonin, with lower potency. Bosentan 10 μM significantly antagonized Et-1-induced contraction in both arteries and airways. We have confirmed contractile responses to both Et-1 and serotonin and inhibition of Et-1-mediated contraction by bosentan in intrapulmonary arteries and airways in rat lung slices. Future studies will apply validated disease models to explore mechanisms underlying altered reactivity and assessment of novel therapeutics for lung diseases, including pulmonary hypertension.
N Whitehead,1 S Miles,2 N Collins,1 G Warner,2 E Kotlyar3
1John Hunter Hospital, Newcastle, Australia; 2Calvary Mater Hospital, Newcastle, Australia; 3St. Vincent's Hospital, Sydney, Australia
Pulmonary hypertension (PH) in hereditary hemorrhagic telangiectasia (HHT) is uncommon, occurring in less than 2% of HHT patients. It can be from true PAH, indistinguishable from Bone Morphogenetic Protein Receptor type II (BMPRII) mutation–associated PAH, or from high-output cardiac failure. There are no controlled trials of therapy in HHT-PAH, with therapy described in limited case reports only. We present an unusual case of HHT-PAH, in which a 20-year-old woman presented with reduced effort capacity to 10 m. Investigations found a large left-lung arteriovenous malformation with shunt of 8%. Severe pulmonary hypertension was confirmed by echocardiography and right heart catheterization. The patient was successfully treated with bosentan and then combination therapy with sildenafil, with marked improvements in 6-minute walk test and functional status. Current evidence and therapeutic options are discussed, including the benefits and risks of arteriovenous malformation closure. We conclude that results of this case study add weight to previous reports supporting the use of bosentan and sildenafil in HHT-associated PAH.