Predictors of electrical storm recurrences in patients with implantable cardioverter-defibrillators.

AIMS: To determine prevalence and predictors of electrical storm recurrences (ES-Rs) in patients with implantable cardioverter-defibrillators (ICDs) as electrical storms (ESs) represent serious clinical events carrying a high risk of mortality. METHODS AND RESULTS: Single-centre study analysing data of consecutive patients receiving an ICD between 1993 and 2008. Electrical storm was defined as ≥ 3 separate ventricular tachyarrhythmic (VT/VF) episodes ≤ 24 h. Nine hundred and fifty-five patients [mean left ventricular ejection fraction (LVEF) 35.7 ± 15.6%] were prospectively followed for 54.2 ± 35.5 months. In 274 of 955 patients (28.7%), 2871 VT/VF episodes were observed. One hundred and fifty-three ES episodes occurred in 63 of 955 patients (6.6%). Thirty-two of 63 patients (50.8%) experienced ≥ 2 ES episodes. Twenty-six of 32 patients (81.2%) with ES-Rs experienced the second ES episode within 1 year after the initial event. Cox regression analysis identified an LVEF ≤ 30% (OR 2.2; 95% CI 1.021-4.856; P = 0.044) and a patient's age >65 years (OR 3.5; 95% CI 1.207-10.176; P = 0.021) to be predictive for ES-Rs. Patients with angiotensin-converting enzyme (ACE) inhibitor therapy were less likely to experience ES-Rs (OR 0.39; 95% CI 0.187-0.817; P = 0.013). CONCLUSIONS: Electrical storm events are not rare in a 'real-world' patient population with ICDs (6.6% in 4.5 years). The risk for ES-Rs, especially within the first year after the initial event, is high. Left ventricular ejection fraction ≤ 30%, age >65 years, and a lack of ACE inhibitor therapy are independent predictors of ES-R.

Role of proinflammatory markers and NT-proBNP in patients with an implantable cardioverter-defibrillator and an electrical storm.

BACKGROUND: Several studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as 3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES. METHODS: Markers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms. RESULTS: All patients had idiopathic dilated cardiomyopathy (n=23) or coronary artery disease (n=63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19+/-10.34 pg/mL, hs-CRP 20.12+/-14.4 mg/L, NT-proBNP 4799+/-4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37+/-5.8 pg/mL (p=0.03), hs-CRP 4.7+/-5.3 mg/dL (p<0.001), NT-proBNP 1913+/-2665pg/mL (p=0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62+/-3.66 pg/mL (p<0.001), hs-CRP 4.1+/-3.4 mg/L (p<0.001), NT-proBNP 1461+/-2281pg/mL (p<0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54+/-10.43 vs. 7.03+/-2.83 pg/mL (p=0.04), hs-CRP 19.07+/-16.07 vs. 6.5+/-3.9 mg/L (p=0.02), NT-proBNP 4218+/-2561 vs. 2099+/-1279 pg/mL (p=0.03)). CONCLUSIONS: Electrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm.

Local paclitaxel delivery after coronary stenting in an experimental animal model.

The goal of this study was to test the safety and efficacy of local paclitaxel delivery via a newly designed application catheter in an experimental animal study. Drug-eluting stents reduce restenosis in comparison to bare-metal stents. The drug-eluting polymer, however, may exert potential thrombogenic and inflammatory effects. A catheter-based local paclitaxel delivery offers further advantages, particularly a homogenous drug transfer into the vessel wall and a pharmacotherapy of the stent edges. In 30 pigs, both bare-metal stent (3.0 x 13 mm) implantation and balloon angioplasty were performed. Ten pigs received subsequent local delivery of paclitaxel-solution via a newly designed catheter (Genie, ACROSTAK corp., Switzerland), 10 animals served as a sham group and received vehicle (0.9% NaCl solution) and 10 animals were used as a control group. All animals were treated with aspirin and clopidogrel to prevent stent thrombosis. After final angiography the vessels were excised 42 days after intervention and prepared for histological and histomorphometric analysis. All coronary arteries showed complete endothelialization 42 days following treatment. Paclitaxel treatment led to a marked reduction of neointimal proliferation either post stent implantation (neointimal area: 1.04 +/- 0.10 mm(2) vs. 2.37 +/- 0.23 mm(2), p < 0.001) or post balloon dilatation (neontimal area: 0.35 +/- 0.14 mm(2), vs. 0.68 +/- 0.24 mm(2), p < 0.01). There were no significant angiographic or histomorphometric differences between the control and the sham group. In both paclitaxel groups neither angiographic edge phenomena nor a significant histomorphometric inflammatory response were found in the treated vessel segments. In conclusion, the local application of paclitaxel via the Genie catheter is safe and effective to significantly reduce the proliferative response post-stent implantation or balloon dilatation in an experimental animal model.

Prospective study of interleukin-6 and the risk of malignant ventricular tachyarrhythmia in ICD-recipients--a pilot study.

OBJECTIVE: We investigated the relationship between interleukin-6 (IL-6) and the risk of experiencing spontaneous ventricular tachyarrhythmia (VT/VF) in patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Cytokine levels predict outcome in patients with advanced heart failure and are elevated in patients with coronary artery disease (CAD). Regarding heart rhythm disturbances, proinflammatory activity could predict the occurrence of atrial fibrillation. There is no data on cytokine levels and the risk of spontaneous VT/VF. METHODS: IL-6 serum concentrations were determined at baseline and follow-up in 47 consecutive ICD-patients with CAD and idiopathic dilated cardiomyopathy (IDC). Data were prospectively correlated with VT/VF-incidence. RESULTS: Thirty-six patients (76.6%) suffered from CAD and 11 (23.4%) from IDC. Mean serum concentrations of IL-6 at baseline and at 9 months follow-up were 6.12+/-4.98 and 4.63+/-6.97. 88 spontaneous VT/VF-events occurred in 13/47 patients (27.7%). Patients with VT/VF had significantly higher IL-6 levels as compared to patients without VT/VF (8.96+/-5.97 vs. 5.04+/-4.16pg/ml at baseline (p =0.03), 7.8+/-4.88 vs. 3.42+/-6.32pg/ml at follow-up (p =0.01)). CONCLUSIONS: Elevated IL-6 serum concentrations were prospectively associated with an increased risk of spontaneous VT/VF-events in ICD-patients with CAD or IDC. These preliminary findings support a possible association of proinflammatory activity and an increased susceptibility to spontaneous VT/VF-events.

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.

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 + 455 ± 50 Ω vs. CD36- 346 ± 53 Ω, p = 0.001; CD31 + 436 ± 43 Ω vs. CD31- 340 ± 55 Ω, p = 0.001; MMP-3 + 400 ± 68 Ω vs. MMP-3- 323 ± 33 Ω, p = 0.03). CONCLUSIONS: Atherosclerotic lesions with abundant neovascularisation (CD31), many scavenger receptor class B expressing cells (CD36) or high amount of MMP-3 immunoreactivity reveal significantly higher impedance values compared to lesions with marginal or no detection of immunoreactivity. Findings suggest that inflammatory processes in vulnerable plaques affect the impedance of atherosclerotic lesions and might therefore be detected by EIS.

Comparison of ventricular tachyarrhythmia characteristics in patients with idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for primary prevention.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathy (DCM) and no history of ventricular tachyarrhythmia (VT/VF) are more limited. HYPOTHESIS: DCM patients with an impaired left ventricular ejection fraction (LVEF) still represent a low arrhythmic risk subgroup in clinical practice. METHODS: ICD stored data of DCM patients with an LVEF ≤35% was compared to data of ICM patients meeting Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility criteria. VT/VF occurrences and electrical storm (ES) events were analyzed. RESULTS: There were 652 patients followed for 50.9 ± 33.9 months. There were 1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of appropriate ICD treatment due to VT/VF or ES events did not differ in both patient populations (log-rank, P>0.05). In patients presenting with VT/VF episodes, mean event rates were comparable in both patient populations (3.2 ± 14.1 for DCM and VT vs 3 ± 13.9 for ICM and VT [P = 0.855], 0.4 ± 1.3 for DCM and VF vs 0.4 ± 1.8 for ICM and VF [P = 0.763], and 0.2 ± 0.7 for DCM and ES vs 0.2 ± 1 for ICM and ES [P = 0.666]). CONCLUSIONS: DCM patients with prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT criteria reveal comparable patterns of VT/VF/ES events during long-term follow-up. Incidence, mean number of events, and time to first event did not differ significantly. Findings support the current guidelines for prophylactic ICD therapy in DCM patients with heart failure.

Electric impedance spectroscopy of human atherosclerotic lesions.

OBJECTIVE: The aim of this in vitro study was to investigate the feasibility of a new highly flexible microelectrode on human tissue and its potential of differentiating atherosclerotic lesions by electric impedance spectroscopy (EIS). METHODS: Electric impedance measurements (EIM) were performed on 148 spots of 7 aortic and 6 femoral human arteries at 1kHz, 10kHz and 100kHz. RESULTS: According to the AHA classification 33 (25%) grade I lesions (PI), 34 (26%) grade II (PII), 21 (16%) grade III (PIII), 21 (16%) grade IV (PIV), 13 (10%) grade Va (PVa) and 10 (8%) grade Vb (PVb) could be identified by histology. At 1kHz, 10kHz and 100kHz the mean electric impedance (MEI) of PI, PII, PIII and PIV was statistically not different. At 100kHz the MEI of PVa showed significantly higher values compared to the MEI of PI (455+/-66Omega vs. 375+/-47Omega, p=0.05), PII (455+/-66Omega vs. 358+/-63Omega, p=0.007), PIII (455+/-66Omega vs. 342+/-52Omega, p=0.003), PIV (455+/-66Omega vs. 356+/-41Omegap=0.013) and the MEI of PVb was significantly increased compared to the MEI of PI (698+/-239Omega vs. 375+/-47Omega, p<0.001), PII (698+/-239Omega vs. 358+/-63Omegap<0.001), PIII (698+/-239Omega vs. 342+/-52Omegap<0.001), PIV (698+/-239Omega vs. 356+/-41Omegap<0.001), PVa (698+/-239Omega vs. 455+/-66Omega, p<0.001). Performing ROC analyses for the detection of grouped PVa/PVb lesions, the largest AUC was found at 100kHz with a cut-off value of 441Omega presenting a sensitivity of 74% and a specificity of 94%. CONCLUSIONS: EIM could be performed on human aortic and femoral tissue. The results show that EIS has the potential to distinguish between different plaque types.