Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Abstract

Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy.

Cardiovascular Research in Friedreich Ataxia

“…One study with 29 subjects with FRDA correlated a serum marker of collagen production, procollagen I carboxy-terminal propeptide, with CMR using late gadolinium enhancement for estimation of cardiac fibrosis. 83 They found that subjects with FRDA had significantly higher baseline procollagen I carboxy-terminal propeptide levels than control subjects did and this strongly correlated with later increases in LV end-diastolic volume. There was no correlation between procollagen I carboxy-terminal propeptide and fibrosis on late gadolinium CMR.…”

Role of cardiovascular magnetic resonance in the clinical evaluation of left ventricular hypertrophy: a 360° panorama

“…In Friedreich's ataxia, besides cellular hypertrophy, the deficiency of frataxin leads to mitochondrial iron accumulation in cardiomyocytes, mitochondrial damage, necrosis and myocardial fibrosis [112][113][114][115][116][117]. This process is depicted by LGE that may be found even in the absence of severe LVH [118,119].…”

Una visión sobre la Neurastenia a través de la Revista Frenopática Española

“…Gran maestro, fundador de dos Facultades de Medicina y profesor en seis, prolífico escritor y destacado investigador, continuó y perfeccionó el arte clásico del diagnóstico físico. Sus contribuciones a la medicina, y en particular a la cardiología, son relevantes (Mehta et al, 2000). En la elaboración de la psicopatología moderna y su taxonomía, el alemán Emelin Kraepelin (1865Kraepelin ( -1926 tuvo un papel clave.…”