Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Alessia Argirò; Roberto Sciagrà; Alberto Marchi; Matteo Beltrami; Enrico Spinelli; Emilia Salvadori; Andrea Bianchi; Mario Mascalchi; Anna Poggesi; Iacopo Olivotto; Francesca Pescini

doi:10.1111/ene.14678

Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Eur J Neurol. 2021 Nov;28(11):3809-3813. doi: 10.1111/ene.14678. Epub 2020 Dec 31.

Authors

Affiliations

¹ Referral Center for Myocardial Diseases, University of Florence, AOU Careggi, Florence, Italy.
² Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
³ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
⁴ Neuroradiology Unit, Department of Services, AOU Careggi, Florence, Italy.
⁵ Neuroradiology Research Program at Meyer Children Hospital, University of Florence, Florence, Italy.
⁶ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
⁷ Stroke Unit, Emergency Department, AOU Careggi, Florence, Italy.
⁸ NEUROFARBA Department, University of Florence, Florence, Italy.

PMID: 33314522
DOI: 10.1111/ene.14678

Abstract

Background and purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients.

Methods: Seventeen patients with genetically confirmed CADASIL, aged <60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by ¹³ NH₃ positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched.

Results: Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p < 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p < 0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI.

Conclusions: CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients.

Keywords: CADASIL; coronary microvascular dysfunction; positron emission tomography.

MeSH terms

Adult
Brain / diagnostic imaging
CADASIL* / complications
CADASIL* / diagnostic imaging
CADASIL* / genetics
Cerebral Infarction
Humans
Magnetic Resonance Imaging
Middle Aged
Receptor, Notch3 / genetics

Substances

Receptor, Notch3