Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy

Paul Knaapen, Tjeerd Germans, Paolo G. Camici, Ornella E. Rimoldi, Folkert J. Ten Cate, Jurrien M. Ten Berg, Pieter A. Dijkmans, Ronald Boellaard, Willem G. Van Dockum, Marco J W Götte, Jos W R Twisk, Albert C. Van Rossum, Adriaan A. Lammertsma, Frans C. Visser

Research output: Contribution to journalArticle

Abstract

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH2-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 ± 0.97 vs. 2.93 ± 0.64 ml·min -1·g-1, P <0.05). In contrast to controls (1.38 ± 0.15 to 1.25 ± 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 ± 0.11 to 0.88 ± 0.18, P <0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P <0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Coronary microcirculation
  • Hypertrophic cardiomyopathy
  • Imaging
  • Outflow tract obstruction

ASJC Scopus subject areas

  • Physiology

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  • Cite this

    Knaapen, P., Germans, T., Camici, P. G., Rimoldi, O. E., Ten Cate, F. J., Ten Berg, J. M., Dijkmans, P. A., Boellaard, R., Van Dockum, W. G., Götte, M. J. W., Twisk, J. W. R., Van Rossum, A. C., Lammertsma, A. A., & Visser, F. C. (2008). Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy. American Journal of Physiology - Heart and Circulatory Physiology, 294(2). https://doi.org/10.1152/ajpheart.00233.2007