L. Selkrig

Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report

BackgroundJuvenile hemochromatosis is the most severe form of iron overloading phenotype. Although rare, it should be suspected in patients who present with hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a clear cause.Case presentationA young Serbian male presenting with end-stage heart failure was referred for extracorporeal membrane oxygenation. An endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His condition was stabilized with biventricular assist devices and he was listed for heart transplantation. Iron chelation therapy was commenced and resulted in rapid removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial recovery such that a successful biventricular assist device explant occurred 131 days after initial implant. Targeted gene sequencing revealed a loss-of-function mutation within the HJV gene, which is consistent with juvenile hemochromatosis.ConclusionsThis rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy.

The prognostic significance of chronotropic incompetence in patients with severe left ventricular systolic function referred for cardiac transplant assessment

An inability to augment heart rate in heart failure patients in response to physical activity (chronotropic incompetence) has been associated with all-cause mortality and hospitalisation. The prevalence of chronotropic incompetence increases with progressive fall in left ventricular ejection fraction and is an independent predictor of cardiovascular mortality. Patients with advanced heart failure, such as those referred for transplantation or mechanical circulatory support, have been under-represented in studies of the pathophysiology of chronotropic incompetence. We sought to clarify the prognostic implication of chronotropic incompetence in this cohort. We retrospectively reviewed the case-notes of all patients with advanced heart failure and a reduced ejection fraction that were referred for cardiac transplant assessment to the outpatients department of a quaternary referral centre between January 2010 and December 2016. As part of cardiac transplant assessment, a symptom limited cardiopulmonary exercise test was performed on an upright cycle ergometer using a step protocol of 5 to 15W increments every minute until exhaustion, with a goal of obtaining an exercise time of 8–12 in accordance with international guidelines. Ventilation and respiratory gas parameters were measured breathby-breath (SensorMedics Corporation) and averaged over 30-s intervals. Peak oxygen uptake (VO2) was defined as the highest 30-s averaged VO2 achieved. VE/VCO2 (minute ventilation/carbon dioxide output) slope was calculated using linear regression of all data points from onset of exercise to the end. Patients with insufficient effort, defined by a respiratory exchange ratio <1.05 were excluded. Chronotropic index (CIx) was defined as: (heart rate (HR) at peak exercise – HR at rest)/(220 – age – HR at rest) and chronotropic incompetence was defined by a CIx value 0.8. Patients had an ejection fraction quantified using nuclear scintigraphy and right heart pressures directly measured using a balloon-tipped catheter as routine. Survival data were available through data linkage with a censor date in February 2017. This study received institutional ethical approval (number 169/17). Data are presented as mean standard deviation (SD). Bivariate correlation was assessed where appropriate with a Pearson’s correlation coefficient (r). A univariate Cox-proportional hazards model was used to calculate a survival function. Ninety patients were studied; mean age was 53.8 years (SD 11.0) and ejection fraction was 23.0% (SD 6.9). Fifteen (16.7%) patients had diabetes, six (6.7%) had chronic obstructive lung disease, 15 (16.7%) were in atrial fibrillation and 37 (41.1%) had an ischaemic aetiology. Eighty-two (91%) patients were on betablockers, 16 (17.7%) were on ivabradine, 41 (45.6%) were on digoxin, 44 (48.9%) were on amiodarone and two (2.2%) were not on any rate lowering medications. Upon symptom limited exercise, only four (4.4%) patients had no evidence of chronotropic incompetence with a CIx threshold >0.8. There was a positive linear correlation between CIx and peak VO2 (r1⁄4 0.53, p< 0.001), peak work load (r1⁄4 0.50, p< 0.001), exercise time (r1⁄4 0.30, p1⁄4 0.006), delta heart rate (r1⁄4 0.937, p< 0.001) and delta systolic blood pressure