Characteristics and Outcomes of a Single-Centre Cohort of Adult Congenital Heart Disease Patients Referred for Heart Transplant.

BACKGROUND: Adult congenital heart disease (ACHD) services increasingly encounter heart failure (HF) in the ageing ACHD population. Optimal timing of referral for heart transplant (HTx) evaluation in this heterogeneous population is complex and ill-defined. We aim to outline the characteristics and outcomes of ACHD patients referred for HTx from a large Australian ACHD centre. METHOD: Retrospective review of ACHD patients referred for HTx from a primary ACHD centre (1992-2021). Database analysis of patient demographics, characteristics, wait-listing, and transplantation outcomes was performed. RESULTS: A total of 45 patients (mean age 37±9.9 years old; 69% male) were referred for HTx with a mean follow-up of 5.9±6.3 years. Of these, 22 of 45 (49%) were listed and transplanted, including one heart-lung transplant. The commonest diagnosis was dextro-transposition of the great arteries (13/45, 29%). Most patients, 33 of 45 (73.3%) had undergone at least one cardiac surgery in childhood. Indications for HTx referral included HF in 34 of 45 (75%), followed by pulmonary hypertension in 7 of 45 (11%). Median transplant wait-list time was 145 days (interquartile range, 112-256). Of the 23 patients not wait-listed, the reasons included clinical stability in 13 of 45 (29%), psychosocial factors in 2 of 45 (4.4%) and prohibitive surgical risk, including multiorgan dysfunction, in 8 of 45 (17.7%). Transplant was of a single organ in most, 21 of 22 (95.5%). Overall mortality was 5 of 22 (22.7%) in those after HTx, and 14 of 23 (60.9%) in those not listed (p=0.0156). CONCLUSIONS: Increasingly, ACHD patients demonstrate the need for advanced HF treatments. HTx decision-making is complex, and increased mortality is seen in those not wait-listed. Ultimately, the referral of ACHD patients for HTx is underpinned by local decision-making and experience, wait-list times and outcomes.

Impact of Late Referral on Cardiac Transplant Outcomes.

BACKGROUND: Late referral for heart transplantation (HTx) is associated with worse patient outcomes. There are no universally accepted definitions of what constitutes a timely referral for HTx assessment. OBJECTIVES: To evaluate the impact of late referral (LR) on HTx outcomes. METHODS: This single-centre retrospective observational study included 80 patients undergoing HTx between 2016-2019. We applied a simple clinical tool, derived from markers of advanced heart failure (HF), to classify LR in HTx patients and assess the impact of LR on HTx outcomes. Outcome measures included duration of intensive care unit (ICU) stay, total hospitalisation stay, cost of transplant admission and one-year mortality. RESULTS: Based upon the clinical profile, LR was defined by the presence of four or more out of 10 criteria for more than 6 months in HTx patients. In this model, 34 patients were timely referrals and 46 were LR. Patients who were LR had: a longer median time between initial diagnosis and referral (3 vs 7 ys; p=0.03); more features of advanced HF, including inotrope requirements (p=0.004); more comorbidities (p=0.014); and hospitalisations (p<0.0001). Late referral was not associated with longer ICU (p=0.14) or hospital stay (p=0.051), however LR incurred greater total in-hospital costs (p=0.011). There was no difference in one-year mortality (6% vs 9%; p=0.64). CONCLUSION: Patients referred late for HTx are more unwell at time of referral and require greater in-hospital resource usage at the time of transplantation. Earlier referral for transplant assessment in patients with advanced HF should be encouraged.

Incidence and Predictors of Eosinophilic Myocardial Hypersensitivity in Patients Receiving Home Dobutamine.

ABSTRACT: We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists. From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. Dobutamine was associated with EMH incidence of 14% (6/43), with zero cases in the milrinone cohort. Mean age was 52 ± 12 years, 22% were female. More than half (62%) were nonischemic dilated cardiomyopathies, the remainder were ischemic cardiomyopathy. Dobutamine dose [250 (200-282) vs. 225 (200-291) µg/min] and duration of therapy [41 (23-79) vs. 53 (24-91) days] was similar between those with and without EMH. Median change in eosinophil count was 0.31 × 10 9 /L in the EMH group compared with only 0.03 × 10 9 /L in the non-EMH cohort, P = 0.02. Increase in peripheral eosinophil count of >0.20 × 10 9 /L demonstrated good discrimination between those with and without EMH, c-statistic 0.83 (95% CI 0.66-1.0). Heart failure hospitalization occurred in 83% of the EMH group versus 59% in the non-EMH group, P = 0.26. Requirement for VAD was significantly higher in the EMH group (83% vs. 41%, P = 0.05). In conclusion, EMH occurred in 14% of patients receiving home dobutamine. Rising eosinophil count should prompt physicians to consider EMH and switch to milrinone to avoid possible escalation to VAD.

Vasoplegia Following Orthotopic Heart Transplantation: Prevalence, Predictors and Clinical Outcomes.

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.

Acute pleiotropic effects of dapagliflozin in type 2 diabetic patients with heart failure with reduced ejection fraction: a crossover trial.

AIMS: This study aimed to explore the rapid effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We studied the functional, echocardiographic, electrophysiological, lung ultrasound, ambulatory blood pressure (BP), microvascular and macrovascular function, and biochemical effects of 2 week treatment with dapagliflozin in 19 type 2 diabetic HFrEF patients in a double-blind, crossover, placebo-controlled trial. Dapagliflozin had no significant effect on clinical, functional, or quality of life parameters. Dapagliflozin reduced systolic BP [114 (105, 131) vs. 106 (98, 113) mmHg, P < 0.01] and diastolic BP [71 (61, 78) vs. 62 (55, 70) mmHg, P < 0.01]. There was no effect on cardiac chamber size, ventricular systolic function, lung ultrasound, or arterial wave reflection. Dapagliflozin increased creatinine [117 (92, 129) vs. 122 (107, 135) µmol/L, P < 0.05] and haemoglobin [135 (118, 138) vs. 136 (123, 144) g/L, P < 0.05]. There was a reduction in ventricular ectopy [1.4 (0.1, 2.9) vs. 0.2 (0.1, 1.4) %, P < 0.05] and an increase in standard deviation of normal heart beat intervals [70 (58, 90) vs. 74 (62, 103), P < 0.05]. Unexpectedly, dapagliflozin increased high-sensitivity troponin T [25 (19, 37) vs. 28 (20, 42) ng/L, P < 0.01] and reduced reactive hyperaemia index [1.29 (1.21, 1.56) vs. 1.40 (1.23, 1.84), P < 0.05]. CONCLUSIONS: After 2 weeks, while multiple parameters supported BP reduction and haemoconcentration with dapagliflozin, reduction in cardiac filling pressure, lung water, and functional improvement was not shown. Reduced ventricular ectopic burden suggests an early antiarrhythmic benefit. The small increase in troponin T and the reduction in the reactive hyperaemia index warrant further mechanistic exploration in this treatment of proven mortality benefit in HFrEF.

Hyponatraemia in heart failure.

Hyponatraemia is common in heart failure (HF). It is estimated that over 20% of patients admitted to hospital with HF have hyponatraemia. It has also been repeatedly shown to be a surrogate marker of increased morbidity and mortality in this specific population. This review focuses on the pathophysiology of hyponatraemia through the activation of neurohormonal cascades in HF, the clinical implications of sustained hyponatraemia and treatment options in the management of this challenging phenomenon.