healthmedicinet

Patients

We prospectively studied consecutive patients referred to our department with palpitations
and exercise-associated premature ventricular beats. One hundred ninety consecutive
patients who were transferred to our magnetic resonance department with confirmed
exercise-associated ventricular ectopies were examined between 1.1.2008 and 30.11.2014
(end of recruitment period). The controls were prospectively scanned and recruited
if they were free of atrial or ventricular premature beats and had no evidence of
structural heart disease as was examined by medical history, echocardiography and
exercise test before the magnetic resonance scan.

Inclusion criteria for the patients were documented PVBs during exercise treadmill
test with a history of palpitations, fatigue or exertional dyspnoea. Exercise-associated
PVBs were defined as one or more ventricular ectopics during exercise including the
first minute after exercise. Patients were excluded if they had a history or findings
suggestive of or confirmed coronary artery disease (history of myocardial infarction,
signs of ischemia on stress tests, transmural scar on echocardiography or subendocardial
or transmural scars on magnetic resonance tomography), dilated or hypertrophic cardiomyopathy,
congenital heart disease, pulmonary hypertension, LV hypertrophy, significant valvular
regurgitation or valvular stenosis, renal failure (creatinine ?1.8 mg/dl, GFR 30).
Further exclusion factors were: chronic alcohol abuse, use of sympathomimetic drugs,
Conn syndrome, chronic loop diuretic treatment, chronic use of laxatives or any other
causes of hypokalemia.

Informed consent was obtained from each patient and control, and the study protocol
conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected
in a priori approval by the institution’s human research committee. After exclusions,
our final cohort comprised 162 patients whom we compared to 70 age- and sex-matched
controls without exercise-induced PVBs.

Cardiovascular magnetic resonance

All images were acquired on a 1.5 T magnetic resonance system (Intera CV 1.5 T, Philips
Medical Systems, Best, the Netherlands) and specifically designed software (Release
11). We used a five-element cardiac phased-array coil combined with a homogeneity
correction algorithm (Constant Level AppeaRance; CLEAR) 22]. Constant level appearance is a homogeneity correction applied to compensate for
signal inhomogeneity attributable to the surface coils. It is equivalent to a SENSE
acquisition with a SENSE factor of one to acquire the sensitivity maps for each synergy
coil element (relative to the body coil sensitivity) that can be used to get a perfect
uniformity correction 22].

Data acquisition was ECG-triggered. We took 2, 3 and 4-chamber long-axis views and
3-D short-axis volume data assessed by steady-state free precession imaging (field
of view 350 mm, matrix 256?×?256, slice thickness 10 mm, no gap, echo time 1.6 ms,
repetition time 4.0 ms, flip angle 60°) to evaluate LV function and dimensions. Phase-contrast
velocity images in the ascending aorta were obtained to measure stroke volume and
rule out significant aortic insufficiency. Functional and morphological data were
evaluated using view forum 6.5. (Philips Medical Systems, Best, the Netherlands).

All patients underwent ECG-triggered, T2-weighted, fast spin echo triple inversion
recovery sequences (STIR) in a short axis view covering the whole left ventricle (seven
to nine acquisitions, slice thickness 10 mm, no gap, field of view 350 mm, matrix
size 512?×?512, flip angle 90°, echo time 100 ms, TR 2 RR intervals). We measured signal intensity
in the myocardial wall and skeletal muscle. We draw five regions of interest into
the septum, five into the anterior, five into the lateral, and five into the inferior
wall of the myocardium. If the regions were inhomogenous we draw five to 10 regions
of interests. This was only the case in 5 % of patients. Five regions of interest
were drawn into the skeletal muscles (erector spinae muscle or lattissimus dorsi)
with a homogenous signal. Relative myocardial signal intensity was calculated by the
ratio of myocardial signal intensity and muscle signal intensity. Resulting from our
previous study findings, we set the cut-off value of an elevated ratio of signal intensity
in STIR images between myocardial and skeletal muscle was at 2.14 20], 21], 23].

The homogeneity of the signal intensity of the region of interest has been studied
intensively at the start of the pilot study in volunteers and patients. A very good
robustness of the performed STIR sequence showing a homogeneous signal at different
time-points in the same volunteers was found and a good inter- and intraobserver variability
was found 20].

Late gadolinium enhancement (LGE) imaging was obtained in all patients 10 min after
the iv. administration of 0.2 mmol/kg gadolinium-diethylenetriaminepentaacetate using
3D inversion recovery turbo gradient echo sequences (2 acquisitions, an inversion
time 230 to 280 ms, field of view 330 mm, matrix size 256?×?256, slice thickness 5 mm,
no gap, echo time 1,4 ms, TR shortest, flip angle 15°) were optimized for each measurement
to guarantee maximum myocardial signal suppression. 3D volume of the left ventricle
was obtained covering the complete left ventricle without gap during two breath holds.
Pericardial enhancement was defined as local or diffuse contrast enhancement. To exclude
partial volume effects, pericardial thickening and enhancement were obtained in short
and long axis views. Locally-thickened pericardium was defined as ?4 mm. All CMR analysis
including STIR and LGE measurements were carried out by one experienced CMR specialist
who was blinded to the clinical characteristics and history of patients and controls.
Clinical data were obtained and collected by our co-workers and study nurse.

Statistical analysis

Data are presented as means and standard deviations for quantitative variables and
as absolute and relative frequencies for categorical variables. Variables between
patients and controls were compared using t-tests for quantitative and Chi-square-tests
for categorical variables. All tests were two-sided and used a significance level
of 0.05 to indicate statistical significance.