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Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament

Iacopo Olivotto1, Francesca Girolami, Roberto Sciagrà

  • 1Referral Center for Myocardial Diseases, Cytogenetics Unit and Department of Clinical Physiopathology, and Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy. olivottoi@aou-careggi.toscana.it

Journal of the American College of Cardiology
|August 13, 2011
PubMed

Insights

Patients with hypertrophic cardiomyopathy (HCM) carrying sarcomere gene mutations have impaired microvascular function and increased fibrosis. This suggests a direct link between genetic mutations and adverse cardiac remodeling, leading to heart failure.

Area of Science:

  • Cardiology
  • Genetics
  • Medical Imaging

Background:

  • Coronary microvascular dysfunction is a key feature of hypertrophic cardiomyopathy (HCM), linked to ventricular remodeling and heart failure.
  • Previous research indicated increased systolic dysfunction in HCM patients with sarcomere myofilament gene mutations.
  • This study investigates the association between genetic status and coronary microvascular dysfunction in HCM.

Purpose of the Study:

  • To assess myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM) patients using positron emission tomography (PET).
  • To evaluate the impact of genetic status on MBF in HCM patients.
  • To explore the relationship between genetic mutations and cardiac remodeling.

Main Methods:

  • Sixty-one HCM patients underwent MBF assessment via (13)N-labeled ammonia PET with dipyridamole stress.
  • Patients were genotyped for 8 key myofilament-encoding genes using automatic DNA sequencing.
  • Cardiac magnetic resonance imaging (CMR) was performed in 35 patients to assess myocardial fibrosis.

Main Results:

  • Fifty-three mutations were identified in 42 patients (69%), designated as genotype-positive.
  • Genotype-positive HCM patients exhibited significantly lower dipyridamole-induced MBF (Dip-MBF) compared to genotype-negative patients (1.7 vs. 2.4 ml/min/g, p < 0.02).
  • A Dip-MBF <1.5 ml/min/g predicted genotype-positive status with 81% accuracy and was independently associated with carrying myofilament gene mutations (HR: 3.52, p = 0.04).
  • Late gadolinium enhancement on CMR was more prevalent in genotype-positive patients (96%) versus genotype-negative patients (67%), p = 0.038.

Conclusions:

  • HCM patients with sarcomere myofilament mutations demonstrate more severe microvascular dysfunction and myocardial fibrosis.
  • These findings highlight a direct link between sarcomere gene mutations and microcirculatory remodeling in HCM.
  • This genetic link may explain the higher long-term prevalence of ventricular dysfunction and heart failure in genotype-positive HCM patients.
Abstract

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