Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: a mitochondrial cardiomyopathy with metabolic syndrome.

AIMS: Cardiomyopathy produces significant mortality in patients with Friedreich ataxia (FA), a genetic disorder that produces intra-mitochondrial iron accumulation. We sought to test the hypothesis that abnormal myocardial perfusion reserve and fibrosis represent early manifestations of cardiomyopathy. METHODS AND RESULTS: Twenty-six patients with genetically proven FA ages 36 ± 12 years without cardiomyopathy and eight controls underwent cardiac magnetic resonance with adenosine. Precontrast imaging for myocardial iron estimation was performed. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial enhancement during vasodilator stress vs. rest. Left ventricular (LV) mass and volumes were computed from short-axis cine images. Serologies included lipids, and platelets were isolated for iron quantification using inductively coupled plasma mass spectrometry. Left ventricular ejection fraction and mass averaged 64.1 ± 8.3% and 62.7 ± 16.7 g/m², respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial perfusion reserve index quantification revealed significantly lower endocardial-to-epicardial perfusion reserve in patients vs. controls (0.80 ± 0.18 vs. 1.22 ± 0.36, P = 0.01). Lower MPRI was predicted by increased number of metabolic syndrome (met-S) features (P < 0.01). Worse concentric remodelling occurred with increased GAA repeat length (r = 0.64, P < 0.001). Peripheral platelet iron measurement showed no distinction between patients and controls (5.4 ± 8.5 × 10⁻7 vs. 5.5 ± 2.9 × 10⁻7 ng/platelet, P = 0.88), nor did myocardial T2* measures. CONCLUSIONS: Patients with FA have abnormal myocardial perfusion reserve that parallels met-S severity. Impaired perfusion reserve and fibrosis occur in the absence of significant hypertrophy and prior to clinical heart failure, providing potential therapeutic targets for stage B cardiomyopathy in FA and related myocardial diseases.

Predictors of early mortality in patients age 80 and older receiving implantable defibrillators.

BACKGROUND: There are no upper age restrictions for implantable defibrillators (ICDs) but their benefit may be limited in patients > or = 80 years with strong competing risks of early mortality. Risk factors for early (1-year) mortality in ICD recipients > or = 80 years of age have not been established. METHODS: Two-center retrospective cohort study to assess predictors of one-year mortality in ICD recipients > or = 80 years of age. RESULTS: Of 2,967 ICDs implanted in the two centers from 1990-2006, 225 (7.6%) patients were > or =80 years of age and followed-up at one of the two centers. Mean age was 83.3 +/- 3.1 years and follow-up time 3.3 +/- 2.6 years. Median survival was 3.6 years (95% confidence interval 2.3-4.9). Multivariate predictors of 1-year mortality included ejection fraction (EF) < or = 20% and the absence of beta-blocker use. Actuarial 1-year mortality of ICD recipients > or = 80 with an EF < or = 20% was 38.2% versus 13.1% in patients 80+ years with an EF > 20% and 10.6% for patients < 80 years with an EF < or = 20% (P < 0.001 for both). There was no significant difference in the risk of appropriate ICD therapy between those patients 80+ years with EF above and below 20%. CONCLUSION: In general, patients > or = 80 years of age who meet current indications for ICD implantation live sufficiently long to warrant device implantation based on anticipated survival alone. However, those with an EF < or = 20% have a markedly elevated 1-year mortality with no observed increase in appropriate ICD therapy, thus reducing the benefit of device implantation in this population.