Left ventricular assist devices for treatment of refractory advanced heart failure: the Western Australian experience.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure. AIMS: Review outcomes of the Western Australian LVAD programme. METHODS: Retrospective database and medical record review. RESULTS: One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort. CONCLUSIONS: Excellent outcomes can be achieved with LVADs in appropriately selected patients.

Current approaches to the diagnosis and management of amyloidosis.

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk-adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.

The Utility of Whole Body 18F-FDG PET-CT in Diagnosing Isolated Cardiac Sarcoidosis: The Western Australian Cardiac Sarcoid Study.

BACKGROUND: It is reported that up to 29-52% of patients with cardiac sarcoidosis (CS) may have isolated cardiac sarcoidosis (ICS). The wide variation in prevalence may be related to the diagnostic methods for assessing extracardiac involvement. Whole-body 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging is a useful and increasingly used technique for screening for extracardiac involvement in cases of suspected ICS. This study aims to determine the rate of isolated cardiac involvement with clinically manifest CS using cardiac 18F-FDG PET-CT. METHODS: We performed a retrospective analysis of data in the West Australian Cardiac Sarcoid (WACaS) Database. After cardiologist review and workup, all cases of proven or probable CS, based on either current Heart Rhythm Society criteria for the diagnosis of CS or local expert consensus were included. Only patients who underwent whole body 18F-FDG PET-CT were included in the final analysis. RESULTS: Fifty-two (52) cases of CS were identified. Data on symptoms, imaging findings, treatment and outcomes were collected. Of the 42 patients who underwent diagnostic 18F-FDG PET-CT, 32 demonstrated changes consistent with CS. Of the 32, 69% were male, mean age 50 years at diagnosis. Only 3/32 (9.4%) patients had ICS. Pulmonary involvement occurred in 91% with varied involvement in other organs. The mean number of extracardiac sites at diagnosis was 2.2. CONCLUSIONS: This study demonstrates the utility of 18F-FDG PET-CT in diagnosing extracardiac organ involvement in cases of CS. With the use of this modality, ICS may be rarer than previously reported.

Analysis of the QuantiFERON-CMV assay, CMV viraemia and antiviral treatment following solid organ transplantation in Western Australia.

Prevention of cytomegalovirus (CMV) infection remains an important aspect of improving long term outcomes of solid organ transplantation and currently relies on prophylactic antiviral medication and early detection of viraemia or disease. Uptake of diagnostic tools to personalise assessment of CMV immunity and guide interpretation of viral testing remains low. We assessed the QuantiFERON-CMV assay in 54 Western Australian recipients of renal, heart, lung or liver allografts to determine the relationship between CMV-specific immunity, viraemia and disease following cessation of antiviral prophylaxis. We carried out an initial validation study which demonstrated that the QuantiFERON-CMV assay is highly precise and strongly correlated with CMV-specific antibodies in 30 healthy blood donors (sensitivity 82%, specificity 95%). In the solid organ transplant recipients we examined, the prevalence of asymptomatic CMV viraemia was high at 61% but only two patients ultimately developed CMV disease, both of whom had negative QuantiFERON-CMV responses, indicating lack of CMV T-cell immunity. The vast majority (94%) of patients who had spontaneous resolution or stability of asymptomatic CMV viraemia without any antiviral treatment had positive QuantiFERON-CMV responses. Positive QuantiFERON-CMV responses at cessation of antiviral prophylaxis were significantly associated with pre-transplant CMV seropositivity and the development of asymptomatic viraemia post-transplantation. Overall, 27% of patients were recommenced on antiviral therapy because of asymptomatic CMV viraemia. Patients with non-reactive QuantiFERON-CMV responses had earlier onset, higher level CMV viraemia compared to those with positive QuantiFERON-CMV responses, although the difference did not reach statistical significance. QuantiFERON-CMV results may contribute to decision making in concert with the serological risk profile, net state of immunosuppression and CMV viral load.

Under-utilisation of ß-blockers in patients with acute coronary syndrome and comorbid chronic obstructive pulmonary disease.

BACKGROUND: ß-blockers are an established mainstay of therapy in acute coronary syndrome (ACS). Despite substantial evidence of their safety and efficacy in chronic obstructive pulmonary disease (COPD) patients, their use in this population remains limited internationally, likely due to fears of inducing bronchospasm. In Australia, little is known about the use of ß-blockers in COPD patients hospitalised for ACS. AIM: To determine if ß-blockers are under-prescribed at discharge for patients with COPD hospitalised for ACS compared to patients without a diagnosis of COPD. METHODS: Retrospective analysis of a tertiary metropolitan hospital computer database was undertaken to identify the first 250 patients hospitalised with ACS from 1 March 2015. RESULTS: Of the 250 patients analysed, there were five in-hospital fatalities, leaving 245 patients for final analysis. Patients with ACS and COPD received fewer ß-blockers at discharge than those with ACS alone (66.7% vs 86.2%, P < 0.05). After controlling for clinically meaningful confounding factors, a logistic regression analysis model determined that, for patients with ACS, the presence of COPD was the only significant predictor of receiving a ß-blocker at discharge. CONCLUSION: Despite strong evidence supporting the use of ß-blockers in COPD patients with ACS, Australian patients with COPD remain under-treated for ACS. More work is needed to alter prescribing attitudes.

Diastolic Pressure Difference to Classify Pulmonary Hypertension in the Assessment of Heart Transplant Candidates.

BACKGROUND: The diastolic pressure difference (DPD) is recommended to differentiate between isolated postcapillary and combined pre-/postcapillary pulmonary hypertension (Cpc-PH) in left heart disease (PH-LHD). However, in usual practice, negative DPD values are commonly calculated, potentially related to the use of mean pulmonary artery wedge pressure (PAWP). We used the ECG to gate late-diastolic PAWP measurements. We examined the method's impact on calculated DPD, PH-LHD subclassification, hemodynamic profiles, and mortality. METHODS AND RESULTS: We studied patients with advanced heart failure undergoing right heart catheterization to assess cardiac transplantation candidacy (N=141). Pressure tracings were analyzed offline over 8 to 10 beat intervals. Diastolic pulmonary artery pressure and mean PAWP were measured to calculate the DPD as per usual practice (diastolic pulmonary artery pressure-mean PAWP). Within the same intervals, PAWP was measured gated to the ECG QRS complex to calculate the QRS-gated DPD (diastolic pulmonary artery pressure-QRS-gated PAWP). Outcomes occurring within 1 year were collected retrospectively from chart review. Overall, 72 of 141 cases demonstrated PH-LHD. Within PH-LHD, the QRS-gated DPD yielded higher calculated DPD values (3 [-1 to 6] versus 0 [-4 to 3] mm Hg; P<0.01) and a greater proportion of Cpc-PH (24% versus 8%; P<0.01) versus the usual practice DPD. Cases reclassified as Cpc-PH based on QRS-gated DPD demonstrated higher pulmonary arterial pressures versus isolated postcapillary pulmonary hypertension (P<0.05). One-year mortality was similar between PH-LHD groups. CONCLUSIONS: The DPD calculated in usual practice is underestimated in PH-LHD, which may classify Cpc-PH patients as isolated postcapillary pulmonary hypertension. The QRS-gated DPD reclassifies a subset of PH-LHD patients from isolated postcapillary pulmonary hypertension to Cpc-PH, which is characterized by an adverse hemodynamic profile.

Clinical Outcomes of Patients Treated With Pulmonary Vasodilators Early and in High Dose After Left Ventricular Assist Device Implantation.

Right ventricular failure (RVF) is common after left ventricular assist device (LVAD) implantation and a major determinant of adverse outcomes. Optimal perioperative right ventricular (RV) management is not well defined. We evaluated the use of pulmonary vasodilator therapy during LVAD implantation. We performed a retrospective analysis of continuous-flow LVAD implants and pulmonary vasodilator use at our institution between September 2004 and June 2013. Preoperative RVF risk was assessed using recognized variables. Sixty-five patients (80% men, 50 ± 14 years) were included: 52% HeartWare ventricular assist device (HVAD), 11% HeartMate II (HMII), 17% VentrAssist, 20% Jarvik. Predicted RVF risk was comparable with contemporary LVAD populations: 8% ventilated, 14% mechanical support, 86% inotropes, 25% BUN >39 mg/dL, 23% bilirubin ≥2 mg/dL, 31% RV : LV (left ventricular) diameter ≥0.75, 27% RA : PCWP (right atrium : pulmonary capillary wedge pressure) >0.63, 36% RV stroke work index <6 gm-m/m(2)/beat. The majority (91%) received pulmonary vasodilators early and in high dose: 72% nitric oxide, 77% sildenafil (max 200 ± 79 mg/day), 66% iloprost (max 126 ± 37 µg/day). Median hospital stay was 26 (21) days. No patient required RV mechanical support. Of six (9%) patients meeting RVF criteria based on prolonged need for inotropes, four were transplanted, one is alive with an LVAD at 3 years, and one died on day 35 of intracranial hemorrhage. Two-year survival was 77% (92% for HMII/HVAD): transplanted 54%, alive with LVAD 21%, recovery/explanted 2%. A low incidence of RVF and excellent outcomes were observed for patients treated early during LVAD implantation with combination, high-dose pulmonary vasodilators. The results warrant further investigation in a randomized controlled study.

Right heart failure and "failure to thrive" after left ventricular assist device: clinical predictors and outcomes.

BACKGROUND: This study determined predictors of early post-operative right heart failure (RHF) and its consequences, as well as predictors of those who clinically thrive longer term after insertion of a continuous-flow left ventricular assist device (LVAD). METHODS: Pre-operative and latest follow-up data were analyzed for 40 consecutive patients who received third-generation centrifugal-flow LVADs. RHF was defined using previously described criteria, including post-operative inotropes, pulmonary vasodilator use, or right-sided mechanical support. Patients were also categorized according to clinical outcomes after LVAD insertion. RESULTS: LVADs were implanted as a bridge to transplantation (BTT) in 33 patients and as destination therapy in 7. Before LVAD implant, 22 patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level 1, and 17 were at level 2. Temporary mechanical assistance was present in 50% of the cohort at LVAD implantation. The 6-month survival/progression to transplant was 92.5%. Average LVAD support time was 385 days (range, 21-1,011 days). RHF developed postoperatively in 13 of 40 patients (32.5%). RHF patients had more severe pre-operative tricuspid incompetence than non-RHF patients. The BTT patients with evidence of RHF had poorer survival to transplant (6 of 11 [54.5%]) than those without RHF (20 of 22 [90.9%]), p = 0.027). There were no other hemodynamic or echocardiographic predictors of short-term RHF. After LVAD, 22 of the 40 patients (55%) thrived clinically. For BTT patients, 20 of 21 (95%) of those who thrived progressed to transplant or were alive at latest follow-up vs 6 of 12 (50%) of those who failed to thrive (FTT; p < 0.005). The thrivers had lower New York Heart Association class (1.5 vs 2.9, p < 0.001), spent less time in the hospital, and had less ventricular tachycardia than the FTT patients. However, no differences were noted in pre-operative INTERMACS level, echocardiographic, hemodynamic, and biochemical indices, or in early post-operative RHF. Age was the only significant predictor: the thrivers were significantly younger (43.7 ± 15.9 vs 60.3 ± 12.6 years; p < 0.001). This age difference was unchanged after exclusion of destination strategy patients. RV function deteriorated in the FTT patients and remained stable in those who thrived. CONCLUSIONS: Early post-operative RHF results in poorer survival/progression to transplantation for BTT patients and is predicted by greater pre-operative tricuspid incompetence. The most important predictor for those who will clinically thrive longer-term after LVAD insertion is younger age.