Cost-Effectiveness of Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation in the Australian Health Care System.

BACKGROUND: Heart transplantation is an effective treatment for end-stage congestive heart failure, however, achieving the right balance of immunosuppression to maintain graft function while minimising adverse effects is challenging. Serial endomyocardial biopsies (EMBs) are currently the standard for rejection surveillance, despite being invasive. Replacing EMB-based surveillance with cardiac magnetic resonance (CMR)-based surveillance for acute cardiac allograft rejection has shown feasibility. This study aimed to assess the cost-effectiveness of CMR-based surveillance in the first year after heart transplantation. METHOD: A prospective clinical trial was conducted with 40 orthotopic heart transplant (OHT) recipients. Participants were randomly allocated into two surveillance groups: EMB-based, and CMR-based. The trial included economic evaluations, comparing the frequency and cost of surveillance modalities in relation to quality-adjusted life years (QALYs) within the first year post-transplantation. Sensitivity analysis encompassed modelled data from observed EMB and CMR arms, integrating two hypothetical models of expedited CMR-based surveillance. RESULTS: In the CMR cohort, 238 CMR scans and 15 EMBs were conducted, versus (vs) 235 EMBs in the EMB group. CMR surveillance yielded comparable rejection rates (CMR 74 vs EMB 94 events, p=0.10) and did not increase hospitalisation risk (CMR 32 vs EMB 46 events, p=0.031). It significantly reduced the necessity for invasive EMBs by 94%, lowered costs by an average of AUD$32,878.61, and enhanced cumulative QALY by 0.588 compared with EMB. Sensitivity analysis showed that increased surveillance with expedited CMR Models 1 and 2 were more cost-effective than EMB (all p<0.01), with CMR Model 1 achieving the greatest cost savings (AUD$34,091.12±AUD$23,271.86 less) and utility increase (+0.62±1.49 QALYs, p=0.011), signifying an optimal cost-utility ratio. Model 2 showed comparable utility to the base CMR model (p=0.900) while offering the benefit of heightened surveillance frequency during periods of elevated rejection risk. CONCLUSIONS: CMR-based rejection surveillance in orthotopic heart transplant recipients provides a cost-effective alternative to EMB-based surveillance. Furthermore, it reduces the need for invasive procedures, without increased risk of rejection or hospitalisation for patients, and can be incorporated economically for expedited surveillance. These findings have important implications for improving patient care and optimising resource allocation in post-transplant management.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Acute Myocarditis and Pericarditis After mRNA COVID-19 Vaccinations-A Single-Centre Retrospective Analysis.

BACKGROUND: With the rapid rollout of COVID-19 vaccinations, numerous associated and suspected adverse events have been reported nationally and worldwide. Literature reporting confirmed cases of pericarditis and myocarditis following SARS-CoV-2 mRNA vaccinations has evolved, with a predominance in adolescent males following the second dose. METHODS: This was a retrospective analysis of all patients presenting to St Vincent's Hospital, Sydney, Australia with suspected COVID-19 vaccine-related myocarditis and pericarditis. The Brighton Collaboration Case Definitions of Myocarditis and Pericarditis were used to categorise patients into groups based on diagnostic certainty. Cardiac magnetic resonance imaging findings were reviewed against updated Lake Louise Criteria for diagnosing patients with suspected myocarditis. RESULTS: We report 10 cases of confirmed, possible or probable myocarditis and pericarditis. The mean age of presentation in the vaccine group was 33±9.0 years. The most common presenting symptom was pleuritic chest pain (n=8, 80%). Eight patients (80%) had electrocardiogram (ECG) abnormalities (n=6 pericarditis, n=2 myocarditis). Five patients (50%) had a minimum 24 hours of cardiac monitoring. One patient had multisystem inflammatory syndrome following vaccination (MIS-V) with severely impaired left ventricular ejection fraction and required admission to the intensive care unit. DISCUSSION AND CONCLUSION: Cardiac complications post mRNA vaccines are rare. Our case series reflects the worldwide data that vaccine-related myocarditis and pericarditis most frequently occur in young males, following the second dose of the vaccine. These cardiac side effects are mild and self-limiting, with adequate responses to oral anti-inflammatories. One patient developed a severe reaction, with no fatal cases.

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.

Clinical characteristics and prognosis of cardiac amyloidosis defined by mass spectrometry-based proteomics in an Australian cohort.

BACKGROUND: Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival. AIM: Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis. METHODS: We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry. RESULTS: A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis. CONCLUSIONS: AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

Efficacy of bortezomib, cyclophosphamide and dexamethasone in cardiac AL amyloidosis.

Cardiac light chain (AL) amyloidosis is a condition with a very poor prognosis. We report a retrospective analysis comparing the traditional melphalan and dexamethasone protocol with cyclophosphamide, bortezomib and dexamethasone in late-stage cardiac AL amyloidosis. The primary end points were overall survival and haematological response. Both regimens provided meaningful responses in this difficult to treat patient group.

Chronic thromboembolic pulmonary hypertension in Australia and New Zealand: An analysis of the PHSANZ registry.

BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand. METHODS: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported. RESULTS: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients. CONCLUSION: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities.

Pulmonary arterial hypertension with below threshold pulmonary vascular resistance.

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25-30 mmHg), PAWP 13 mmHg (IQR 11-14 mmHg) and PVR 2.2 Wood units (IQR 1.9-2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280-416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7-96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32-101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and "borderline" PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.

BACKGROUND AND OBJECTIVE: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. METHODS: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. RESULTS: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. CONCLUSION: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.

Pharmacological Treatment of Pulmonary Arterial Hypertension in Australia: Current Trends and Challenges.

BACKGROUND: Combination drug therapy for pulmonary arterial hypertension (PAH) is the international standard of care for most patients, however in Australia there are barriers to drug access. This study evaluates current treatment of PAH patients in Australia and the consistency of therapy with international guidelines. METHODS: Cross-sectional analysis of patients with Group 1 PAH enrolled in the Pulmonary Hypertension Society of Australia and New Zealand Registry (PHSANZ) at 31 December 2017. Drug treatment was classified as monotherapy or combination therapy and adequacy of treatment was determined by risk status assessment using the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculator. Predictors of monotherapy were assessed using a generalised linear model with Poisson distribution and logarithmic link function. RESULTS: 1,046 patients met the criteria for analysis. Treatment was classified as monotherapy in 536 (51%) and combination therapy in 510 (49%) cases. Based on REVEAL 2.0, 184 (34%) patients on monotherapy failed to meet low-risk criteria and should be considered inadequately treated. Independent predictors of monotherapy included age greater than 60 years (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.09-1.38; p=0.001), prevalent enrolment in the registry (RR 1.21 [95%CI 1.08-1.36]; p=0.001) and comorbid systemic hypertension (RR 1.17 [95%CI 1.03-1.32]; p=0.014), while idiopathic/heritable/drug-induced PAH subtype (RR 0.85 [95%CI 0.76-0.96]; p=0.006), functional class IV (RR 0.50 [95%CI 0.29-0.86]; p=0.012), increased right ventricular systolic pressure (RR 0.99 [95%CI 0.99-1.00]; p<0.001) and increased pulmonary vascular resistance (RR 0.96 [95%CI 0.95-0.98]; p<0.001) were less likely to be associated with monotherapy. CONCLUSIONS: Most Australian PAH patients are treated with monotherapy and a significant proportion remain at risk of poor outcomes. This is below the standard of care recommended by international guidelines and at risk patients should be escalated to combination therapy.

Diagnostic Performance of Pulmonary Capacitance at Rest and During Exercise in Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Reliable markers of early disease are needed in pulmonary arterial hypertension (PAH). As measures of the contribution of abnormal vascular compliance to overall vascular resistance, resting and exercise pulmonary capacitance-defined as the stroke volume divided by the change in pulmonary pulse pressure-may be sensitive markers of early disease. METHODS: We examined all patients in our pulmonary hypertension database with idiopathic PAH, who had undergone rest and exercise right heart catheterisation in one sitting. Standard haemodynamic measurements were obtained, including pulmonary capacitance. These results were compared to age- and sex-matched normal controls. RESULTS: We analysed 27 right heart catheterisations in idiopathic PAH patients and 23 in controls. Mean pulmonary artery pressure (MPAP), mean pulmonary capillary wedge pressure (mPCWP), pulmonary vascular resistance (PVR) and right ventricular stroke work index (RVSWI) were significantly higher at baseline in diseased patients, while Cardiac Index (CI) and pulmonary capacitance were significantly lower. MPAP, mPCWP, cardiac index and RVSWI increased significantly in both groups with exercise. Pulmonary capacitance decreased significantly in both groups. Pulmonary vascular resistance decreased with exercise in the control group only. Capacitance and PVR were inversely correlated at rest (time-constant of 0.79s) and with exercise (time-constant of 0.56s). The receiver operating characteristic (ROC) curve for capacitance as a diagnostic marker demonstrated an AUC of 0.96 at rest and 0.95 with exercise. CONCLUSIONS: In idiopathic pulmonary arterial hypertension (IPAH) there is a reduction in pulmonary capacitance at baseline and left-shift of the inverse capacitance-PVR relationship with exercise. Both resting and exercise pulmonary capacitance have potential as diagnostic markers in early disease.

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.

The benefit of exercise training in pulmonary hypertension: a clinical review.

Pulmonary hypertension (PH) is a clinical condition characterised by raised pulmonary artery pressure, which results in increased right ventricular afterload and dyspnoea. This is accompanied by reduced exercise capacity, quality of life and, eventually, death. An increasing range of targeted medications has transformed the treatment of pulmonary arterial hypertension, a specific type of PH. Supervised exercise training is recommended as part of a multifaceted management plan for PH. However, many questions remain regarding how exercise training improves exercise capacity and quality of life. The optimal exercise regimen (frequency, timing, duration and intensity) also remains unclear. This review provides an update on the pathophysiology of exercise impairment in PH, suggests mechanisms by which exercise may improve symptoms and function and offers evidence-based recommendations regarding the frequency and intensity of an exercise programme for patients with PH.

Primary percutaneous coronary intervention for inferior ST-segment elevation myocardial infarction in a patient supported by the HeartWare left ventricular assist device.

A 63-year-old man with an ischaemic cardiomyopathy, supported by the HeartWare left ventricular assist device (LVAD), presented with ventricular tachycardia and inferior ST-elevation myocardial infarction (STEMI) with associated acute right ventricular (RV) dysfunction. He underwent primary percutaneous coronary intervention with balloon angioplasty and placement of three drug-eluting stents in the proximal-to-mid right coronary artery. Post-procedure, ventricular arrhythmias abated, RV systolic dysfunction resolved and RV size normalised. Percutaneous coronary intervention (PCI) facilitated by the use of miniaturised percutaneous LVAD has become an increasingly available treatment option for high-risk patients. PCI in patients on established full mechanical circulatory support is not a common occurrence. Indeed, to our knowledge, this is the first case of primary percutaneous coronary intervention on an LVAD-supported heart reported in the medical literature. The case raises several specific issues that are of peculiar interest to clinicians involved in the care of patients supported by mechanical assist devices who experience an acute coronary syndrome requiring emergent revascularisation.

Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.

BACKGROUND: Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. METHODS: The recipients were patients at St Vincent's Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. FINDINGS: Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3-8·1 mmol/L for patient 1, 6·79-6·48 mmol/L for patient 2, and 7·6-7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6-3·6 mmol/L, 2·8-2·3 mmol/L, and 2·69-2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. INTERPRETATION: Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. FUNDING: NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.

Impact of Implantable Cardioverter Defibrillators on Survival of Patients with Centrifugal Left Ventricular Assist Devices.

BACKGROUND: Both implantable cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) have a positive impact on survival in the heart failure population. We sought to determine whether these positive effects on survival are additive or whether LVAD therapy supersedes ICD therapy. METHOD: We analyzed survival data of patients implanted with nonpulsatile LVADs between October 2004 and March 2013. Survival in patients with ICDs (n = 64) was compared to those without ICDs (n = 36). Patients exited the study at the time of heart transplantation or death. RESULTS: A total of 100 patients underwent LVAD implantation during this time. Patients had a mean follow-up time of 364 ± 295 days. Death occurred in 15 (38%) patients in the no ICD group versus 18 (30%) in the ICD group. Univariate analysis demonstrated a marginal early survival benefit at up to 1 year post-LVAD implant in the ICD cohort; however, at time points greater than 1 year there was no statistically significant benefit in ICD therapy in LVAD patients (P = 0.56). Multivariate analysis did not show any significant predictor of survival. There were no patients who died of sudden cardiac death. There was no significant difference in the time to heart transplantation (443 days ± 251 no ICD vs 372 days ± 277 ICD, P = 0.37). CONCLUSION: The benefit of ICD therapy in the setting of continuous flow LVAD therapy is uncertain. Although prolonged ventricular arrhythmias (VAs) may potentially impact on patient survival, LVAD therapy is beneficial in prevention of sudden cardiac death due to VAs.

Normalisation of haemodynamics in patients with end-stage heart failure with continuous-flow left ventricular assist device therapy.

BACKGROUND: New generation continuous-flow left ventricular assist devices (LVADs) utilise centrifugal pumps. Data concerning their effect on patient haemodynamics, ventricular function and tissue perfusion is limited. We aimed to document these parameters following HeartWare centrifugal continuous-flow LVAD (HVAD) implantation and to assess the impact of post-operative right heart failure (RHF). METHODS: We reviewed 53 consecutive patients (mean age 49.5 ± 14.1 yrs) with HVAD implanted in the left ventricle, at St. Vincent's Hospital, Sydney, between January 2007 and August 2012. Available paired right heart catheterisation (n=35) and echocardiography (n=39) data was reviewed to assess response of invasive haemodynamics and ventricular function to LVAD support. RESULTS: A total of 28 patients (53%) were implanted from interim mechanical circulatory support. Seventeen patients (32%) required short-term post-implant veno-pulmonary artery extracorporeal membrane oxygenation. At 100 ± 61 days post-implant, mean pulmonary artery pressure and mean pulmonary capillary wedge pressure decreased from 38.8 ± 7.7 to 22.9 ± 7.7 mmHg and 28.3 ± 6.4 to 13.4 ± 5.4 mmHg respectively (p<0.001). LV end diastolic diameter decreased from 71.3 ± 12.7 to 61.1 ± 13.7 mm and LV end-systolic diameter from 62.7 ± 12.3 to 53.9 ± 14.4mm (p<0.001). Aortic regurgitation remained trivial. Serum sodium increased from 133.3 ± 5.7 to 139.3 ± 2.8 mmol/L and creatinine decreased from 109.1 ± 42.5 to 74.3 ± 26.2 µmol/L (p<0.001). Across the entire cohort, the six-month survival/transplant rate was significantly lower for RHF patients (72.2%, n=18) compared to those without (96.9%, n=35, p=0.01). CONCLUSIONS: HVAD support improves haemodynamics, LV dimensions and renal function. Following implantation with a centrifugal continuous-flow LVAD, RHF remains a significant risk with a tendency to worse outcomes in the short to medium term.

Comparative adherence of macitentan versus ambrisentan and bosentan in Australian patients with pulmonary arterial hypertension: a retrospective real-world database study.

AIM: Bosentan, ambrisentan, and macitentan are endothelin receptor antagonists (ERAs), currently available in Australia for treatment of pulmonary arterial hypertension (PAH). This study assessed the comparative adherence of these ERAs for PAH in Australian patients. METHODS: This retrospective, observational study used data for adults with PAH from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset (01/2006-10/2020). The primary outcome was treatment adherence (i.e. receiving ≥80% of ERA doses over 12 months). Secondary outcomes were time to treatment change (add-on or switch) and overall survival. RESULTS: The study included 436 patients who took bosentan (n = 200), ambrisentan (n = 69), or macitentan (n = 167). Treatment adherence was significantly greater in patients who received macitentan (65.3%) versus ambrisentan (56.5%) and bosentan (58.0%), with odds ratios (ORs; 95% CI) of 0.51 (0.30-0.88; p = 0.016) for bosentan versus macitentan and 0.48 (0.24-0.96; p = 0.037) for ambrisentan versus macitentan. The median time to treatment change was 47.2 and 43.4 months for bosentan and ambrisentan, respectively (not calculated for macitentan because of insufficient duration of data). LIMITATIONS AND CONCLUSIONS: Real-world data for Australian patients with PAH showed that treatment adherence for ERAs was suboptimal. Adherence was higher for macitentan compared with ambrisentan and bosentan.