Feasibility and potential benefit of pre-procedural CMR imaging in patients with ischaemic cardiomyopathy undergoing cardiac resynchronisation therapy.

AIM: To determine the feasibility and potential benefit of a full cardiac magnetic resonance (CMR) work-up for assessing the location of scarred myocardium and the region of latest contraction (LCR) in patients with ischaemic cardiomyopathy (ICM) undergoing cardiac resynchronisation therapy (CRT). METHODS: In 30 patients, scar identification and contraction timing analysis was retrospectively performed on CMR images. Fluoroscopic left ventricular (LV) lead positions were scored with respect to scar location, and when placed outside scar, with respect to the LCR. The association between the lead position with respect to scar, the LCR and echocardiographic LV end-systolic volume (LVESV) reduction was subsequently evaluated. RESULTS: The CMR work-up was feasible in all but one patient, in whom image quality was poor. Scar and contraction timing data were succesfully displayed on 36-segment cardiac bullseye plots. Patients with leads placed outside scar had larger LVESV reduction (-21 ± 21%, n = 19) compared to patients with leads within scar (1 ± 25%, n = 11), yet total scar burden was higher in the latter group. There was a trend towards larger LVESV reduction in patients with leads in the scar-free LCR, compared to leads situated in scar-free segments but not in the LCR (-34 ± 14% vs -15 ± 21%, p = 0.06). CONCLUSIONS: The degree of reverse remodelling was larger in patients with leads situated in a scar-free LCR. In patients with leads situated within scar there was a neutral effect on reverse remodelling, which can be caused both by higher scar burden or lead position. These findings demonstrate the feasibility of a CMR work-up and potential benefit in ICM patients undergoing CRT.

How I do it: feasibility of a new ultrasound probe fixator to facilitate high quality stress echocardiography.

BACKGROUND: Stress echocardiography (SE) has recently regained momentum as an important diagnostic tool for the assessment of both ischemic and non-ischemic heart disease. Performing SE during physical exercise is challenging due to a suboptimal patient position and vigorous movements of the patient's chest. This hampers a stable ultrasound position and reduces the diagnostic performance of SE. A stable ultrasound probe position would facilitate producing high quality images during continuous measurements. With Probefix (Usono, Eindhoven, The Netherlands), a newly developed tool to fixate the ultrasound probe to the patient's chest, stabilization of the probe during physical exercise is possible. IMPLEMENTATION AND RESULTS: The technique of SE with the Probefix and its' feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound probe to the patient's chest, using two chest straps and a fixation device. The ultrasound probe position and angle may be altered with a relative high degree of freedom. We tested the Probefix for continuous echocardiographic imaging in 12 study subjects during supine and upright ergometer stress tests. One patient was unable to perform exercise and in two study subjects good quality images were not achieved. In the other patients (82%) a stable probe position was obtained, with subsequent good quality echocardiographic images during SE. CONCLUSION: We have demonstrated the feasibility of the Probefix support during ergometer tests in supine and upright positions and conclude that this external fixator may facilitate continuous monitoring of cardiac function in a group of patients.

Deleterious acute and chronic effects of bradycardic right ventricular apex pacing: consequences for arrhythmic outcome.

In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min. ECG, and left (LV) and right ventricular (RV) monophasic action potentials durations (MAPD) were recorded; activation time (AT) and activation recovery interval (ARI) were determined from ten distinct LV electrograms; interventricular mechanical delay (IVMD) and time-to-peak strain (TTP) of the LV septal and lateral wall (ΔTTP: lateral wall minus septal wall) were obtained echocardiographically. Dofetilide (25 µg/kg/5 min) was infused to study TdP inducibility. In baseline AAVB, in comparison to SR, RVA bradypacing acutely increased QT interval, LV, and RVMAPD. Echocardiographic IVMD and ΔTTP were initially increased, which was partially corrected after 3 weeks of RVA pacing (IVMD: 22 ± 13 vs. 42 ± 11 vs. 31 ± 6 ms; ΔTTP: -2 ± 47 vs. -114 ± 38 vs. -36 ± 22 ms). QT interval (362 ± 23 vs. 373 ± 29 ms), LVMAPD (245 ± 18 vs. 253 ± 22 ms), RVMAPD (226 ± 26 vs. 238 ± 31 ms), and mean LV-ARI (268 ± 5 vs. 267 ± 6 ms) were not significantly changed after 3 weeks of RVA pacing. During AAVB, dofetilide increased mean LV-ARI (381 ± 11 ms) with largest increases in the later activated basal areas (slope AT-ARI: +0.96). In contrast with acute RVA pacing, 3 week pacing increased TdP inducibility (0/13 vs. 11/21) and mean LV-ARI (484 ± 18 ms), while the slope of AT-ARI responded differently on dofetilide (-2.37), with larger APD increases in the early region. The latter was supported at the molecular level: reduced RNA expressions of three repolarization-related ion channel genes in early (KCNQ1, KCNH2, and KCNJ2) versus two in late regions (KNCQ1 and KCNJ2). In conclusion, bradycardic RVA pacing acutely induced LV intra- and interventricular mechanical dyssynchrony, which was partially reversed after 3 weeks of pacing (remodeling). The latter occurred without apparent baseline electrical effects. However, dofetilide clearly unmasked (region-specific) arrhythmic consequences of remodeling.

Echocardiography and cardiac resynchronisation therapy, friends or foes?

Echocardiography is used in cardiac resynchronisation therapy (CRT) to assess cardiac function, and in particular left ventricular (LV) volumetric status, and prediction of response. Despite its widespread applicability, LV volumes determined by echocardiography have inherent measurement errors, interobserver and intraobserver variability, and discrepancies with the gold standard magnetic resonance imaging. Echocardiographic predictors of CRT response are based on mechanical dyssynchrony. However, parameters are mainly tested in single-centre studies or lack feasibility. Speckle tracking echocardiography can guide LV lead placement, improving volumetric response and clinical outcome by guiding lead positioning towards the latest contracting segment. Results on optimisation of CRT device settings using echocardiographic indices have so far been rather disappointing, as results suffer from noise. Defining response by echocardiography seems valid, although re-assessment after 6 months is advisable, as patients can show both continuous improvement as well as deterioration after the initial response. Three-dimensional echocardiography is interesting for future implications, as it can determine volume, dyssynchrony and viability in a single recording, although image quality needs to be adequate. Deformation patterns from the septum and the derived parameters are promising, although validation in a multicentre trial is required. We conclude that echocardiography has a pivotal role in CRT, although clinicians should know its shortcomings.

Echo response and clinical outcome in CRT patients.

BACKGROUND: Change in left ventricular end-systolic volume (∆LVESV) is the most frequently used surrogate marker in measuring response to cardiac resynchronisation therapy (CRT). We investigated whether ∆LVESV is the best measure to discriminate between a favourable and unfavourable outcome and whether this is equally applicable to non-ischaemic and ischaemic cardiomyopathy. METHODS: 205 CRT patients (age 65 ± 12 years, 69 % men) were included. At baseline and 6 months echocardiographic studies, exercise testing and laboratory measurements were performed. CRT response was assessed by: ∆LVESV, ∆LV ejection fraction (LVEF), ∆ interventricular mechanical delay, ∆VO2 peak, ∆VE/VCO2, ∆BNP, ∆creatinine, ∆NYHA, and ∆QRS. These were correlated to the occurrence of major adverse cardiac events (MACE) between 6 and 24 months. RESULTS: MACE occurred in 19 % of the patients (non-ischaemic: 13 %, ischaemic: 24 %). ∆LVESV remained the only surrogate marker for CRT response for the total population and patients with non-ischaemic cardiomyopathy, showing areas under the curve (AUC) of 0.69 and 0.850, respectively. For ischaemic cardiomyopathy, ∆BNP was the best surrogate marker showing an AUC of 0.66. CONCLUSION: ∆LVESV is an excellent surrogate marker measuring CRT response concerning long-term outcome for non-ischaemic cardiomyopathy. ∆LVESV is not suitable for ischaemic cardiomyopathy in which measuring CRT response remains difficult.