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CLINICAL RESEARCH: HEART FAILURE/TRANSPLANTATION

The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure

Jan Sundell, MD^*, Erik Engblom, MD, Juhani Koistinen, MD, Antti Ylitalo, MD, Alexandru Naum, MD^*, Kira Q. Stolen, PhD^*, Riikka Kalliokoski, MSc^*, Stephan G. Nekolla, MD, K. E. Juhani Airaksinen, MD, Jeroen J. Bax, MD^|| and Juhani Knuuti, MD^*,*

^* Turku PET Centre, Turku, Finland
Departments of Medicine, University of Turku, Turku, Finland
Department of Medicine, Satakunta Central Hospital, Pori, Finland
Klinik und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Muenchen, Germany
^|| Department of Cardiology, Leiden University, Leiden, Netherlands

Manuscript received March 26, 2003; revised manuscript received June 26, 2003, accepted October 13, 2003.

^* Reprint requests and correspondence: Dr. Juhani Knuuti, Turku PET Centre, Turku University Central Hospital, P.O. Box 52, FIN-20521 Turku, Finland.
jknuuti{at}utu.fi

OBJECTIVES: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated.

BACKGROUND: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF).

METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 ± 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h. Left ventricular function was measured using echocardiography and oxidative metabolism using [¹¹C]acetate positron emission tomography. Both measurements were performed at rest and during dobutamine-induced stress (5 µg/kg/min). Basal- and adenosine-stimulated (140 µg/kg/min) myocardial blood flow were quantitated using [¹⁵O]water.

RESULTS: During CRT off, LV stroke volume was significantly reduced at rest (72 ± 18 ml vs. 63 ± 15 ml, p < 0.05), but LV oxidative metabolism (K_mono) remained unchanged (0.046 ± 0.008 vs. 0.054 ± 0.016 min^–1) leading to a significant deterioration of myocardial efficiency of forward work (from 48.2 ± 16.7 to 36.6 ± 11.7 mm Hg·l/g, p < 0.05). During dobutamine-induced stress, stroke volume and K_mono values were not different whether CRT was on or off. However, myocardial efficiency (56.1 ± 16.1 vs. 49.8 ± 18.0 mm Hg·ml·g^–1·min^–1, p = 0.099) and metabolic reserve, the response of K_mono to dobutamine (0.023 ± 0.014 vs. 0.013 ± 0.014 min^–1, p = 0.09), tended to reduce when CRT was switched off. Cardiac resynchronization therapy had no effects on myocardial perfusion. Natriuretic peptides increased significantly during CRT-off period.

CONCLUSIONS: Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.

Abbreviations and Acronyms   CRT = cardiac resynchronization therapy   HF = heart failure   Kmono = [11C]acetate clearance rate   LV = left ventricle   NYHA = New York Heart Association   PET = positron emission tomography   ROI = region of interest   S-ANPN = serum N-terminal atrial natriuretic peptide   S-proBNP = serum N-terminal pro-brain natriuretic peptide   [11C]acetate = carbon-11-labeled acetate   [15O]water = oxygen-15-labeled water

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