Effects of Cardiac Resynchronization Therapy on the Microcirculation
(CaRe-Mi)

Cardiac resynchronization therapy (CRT) is accepted as an adjunctive
therapeutic option for patients with congestive heart failure (CHF) with
optimal pharmacologic regimen. It is known that CRT improves the systemic
circulation, physical performance, quality of life and outcome. However, not
all patients treated do respond to cardiac resynchronization therapy. The
reasons for this are not completely understood. Besides various possible ways
of pacing the heart, the different responses of the microcirculation to CRT,
and therefore different supply of organs with oxygen and nutrients, may account
for the varying outcome. In a pilot study, in responders to CRT, improvement of
the microcirculation has been found. However, the relation between cardiac and
systemic hemodynamics remains to be elucidated.

The primary objective of this project is to test the hypothesis that CRT exerts
beneficial effects on the microcirculation by recruitment of capillaries. The
secondary objective is to compare the microcirculatory with the hemodynamic
parameters and the changes in the microcirculation in responders versus
non-responders to CRT.

Single-center, case-control study

5 different areas of the sub-lingual microcirculation will be imaged by use of
Sidestream Dark Field (SDF) imaging hand microscope. Images will be acquired
during: no pacing (if the patient is not pacing dependent), monoventricular
pacing, biventricular pacing, and after sublingual application of
pharmacological vasodilatation with local acetylcholine. Each pacing set-up
will have a pacing rate of 60 per minute and will be maintained for 15 minutes.
At each measuring time point heart rate, blood pressure, velocity time integral
(VTI) over the aortic valve and cardiac output will be recorded non-invasively.
Semi-quantitative posthoc analysis of the recordings of the microcirculation
will be performed using the Microvascular Analyzing Software.

The patient does not have to change habits, therapy or follow a special diet
before or after this study. All measurements performed during the study are
painless and non-invasive. The study will last one visit of 1 hour. The
patients are asked to fill in a form asking for generalities, cardiovascular
risk factors, Canadian Cardiovascular Society (CCS) and NYHA scores and
pharmacologic regimen. A 12 lead ECG is performed. The CRT device is programmed
transcutaneously. At each programming step non-invasive, painless sublingual
imaging of the microcirculation is performed by means of a hand held microscope
(SDF) during 5 sets of 5-10 minutes. Pauses in the imaging can be interposed as
requested by the patient. At each pacing step the VTI over the aortic valve is
measured by transthoracic echocardiography. The local application of
acetylcholine (10e-2 M) confers a minimal risk for systemic symptoms.