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CLINICAL RESEARCH: HYPERTROPHIC CARDIOMYOPATHY

Relevance of Coronary Microvascular Flow Impairment to Long-Term Remodeling and Systolic Dysfunction in Hypertrophic Cardiomyopathy

Iacopo Olivotto, MD^_*,_*, Franco Cecchi, MD^_*, Roberto Gistri, MD^_*, Roberto Lorenzoni, MD, Giampaolo Chiriatti, MD, Francesca Girolami, BSc, Francesca Torricelli, BSc and Paolo G. Camici, MD, FACC, FRCP^||,¶

^_* Regional Referral Center for Myocardial Diseases, Florence, Italy
Cytogenetics, Azienda Ospedaliera Careggi, Florence, Italy
Cardiology Unit, Ospedale di Lucca, Lucca, Italy
Cardiology Unit, Ospedale di Pescia, Pescia, Italy
^|| Consiglio Nazionale delle Ricerche, Institute of Clinical Physiology, Pisa, Italy
^¶ Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College, London, United Kingdom

Manuscript received May 27, 2005; revised manuscript received September 30, 2005, accepted October 17, 2005.

^_* Reprint requests and correspondence: Dr. Iacopo Olivotto, Centro di Riferimento per le Cardiomiopatie, Cardiologia San Luca, Azienda Ospedaliera Universitaria Careggi, Viale Pieraccini 19, 50134 Firenze, Italy (Email: olivottoi{at}ao-careggi.toscana.it).

OBJECTIVES: This study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM).

BACKGROUND: A subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism.

METHODS: Fifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 ± 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) <50%.

RESULTS: The Dip-MBF was blunted in HCM patients compared with a group of healthy control patients (1.50 ± 0.69 ml/min/g vs. 2.71 ± 0.94 ml/min/g; p < 0.001). At final evaluation, 11 patients (22%) had an LVEF <50%; in most (n = 7), systolic dysfunction was associated with a significant increase in LV cavity dimensions (>5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 ± 0.38 ml/min/g vs. 1.63 ± 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 ± 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (<1.1 ml/min/g; relative hazard, 7.5; p = 0.038) and an end-diastolic LV dimension in the highest tertile (>45 mm; relative hazard, 12.3; p = 0.031).

CONCLUSIONS: Severe microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM.

Abbreviations and Acronyms   Dip = dipyridamole   HCM = hypertrophic cardiomyopathy   LV = left ventricle/ventricular   MBF = myocardial blood flow   NYHA = New York Heart Association   PET = positron emission tomography

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