Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Background: Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. Methods and Results: EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455650 V vs. CD36- 346653 V, p = 0.001; CD31+436643 V vs. CD31- 340655 V, p = 0.001; MMP-3+ 400668 V vs. MMP-3- 323633 V, p = 0.03)

Impact of shocks on mortality in patients with ischemic or dilated cardiomyopathy and defibrillators implanted for primary prevention.

BACKGROUND: Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM), the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM) or DCM and defibrillators (ICD) implanted for primary prevention. METHODS AND RESULTS: Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%). During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2%) experienced ≥1 appropriate and 51 out of 561 patients (9.1%) ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects). Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96-2.28, log rank p = 0.072). The effect was significant in ICM patients (HR 1.61, 95% CI 1.00-2.59, log rank p = 0.049) but not in DCM patients (HR 1.03, 95% CI 0.36-2.96, log rank p = 0.96). Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24-3.63, p = 0.005). The effect was driven by ICM patients (HR 2.48, 95% CI 1.41-4.37, p = 0.001), as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083-4.75, p = 0.65). Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns). CONCLUSION: Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within the first 4 years after device implantation

Experimental setup of the impedance measurement system.

<p>Experimental setup of the impedance measurement system.</p

ROC curves computed by determined impedance values (at 100 kHz).

<p>ROC curves separating samples of abundant and minor/no staining with good (MMP-3) to excellent (CD31, CD36) accuracy.</p

Influence of inflammation on impedance values determined by EIS (box plots).

<p>Influence of inflammation on impedance values determined by EIS (box plots).</p

Value of electric impedance measurements in detecting inflammatory processes defined by different markers of inflammation.

<p>Value of electric impedance measurements in detecting inflammatory processes defined by different markers of inflammation.</p

Cross section depicting an advanced lesion type Va.

<p>Movats staining, magnification 20×. LC: Characteristic lipid core. FC: Thick fibrous cap with yellow staining of collagen fibers and red-colored smooth muscle cells. M: Media. Arrow: Microhemorrhages, typically found at the lateral margin of the lipid core (red: stained fibrin).</p

A-C. Kaplan Meier survival estimation after appropriate shocks (complete follow-up).

<p>A significant association between appropriate shocks and survival is only determined in patients with ICM.</p

Comparison of VTA episodes and appropriate shocks in patients with DCM and ICM.

<p>app. shock  =  appropriate shock; DCM  =  dilated cardiomyopathy; ES  =  electrical storm; ICM  =  ischemic cardiomyopathy; VF  =  ventricular fibrillation; VT  =  ventricular tachycardia; VTA  =  ventricular tachyarrhythmia.</p

A-B. Kaplan Meier survival estimation after occurrence of appropriate shocks before median follow-up.

<p>Kaplan Meier Curves displaying that the significant effect of appropriate shocks on survival in the overall patient population is primarily driven by the ICM subgroup.</p