Determinants of T-wave alternans and beat-to-beat variability of repolarization in ischemic cardiomyopathy

In this thesis we have explored strategies to predict the risk of arrhythmic sudden cardiac death (SCD) in patients with ischemic cardiomyopathy after myocardial infarction (MI). We focus on the efficacy of current risk stratification in implantable cardioverter-defibrillator (ICD) patients and the interaction between T-wave alternans (TWA), beat-to-beat variability of repolarization (BVR) and post-MI ventricular remodeling. In chapter 1 we evaluated the value of classical risk factors to discriminate useful from useless ICD implantations in ischemic cardiomyopathy patients. Although low left ventricular ejection fraction (LVEF) is the key parameter to warrant prophylactic ICD implantation, it was also related to a higher number of futile ICD implantations. This finding emphasizes the problematic link between low LVEF and ICD-resistant mortality. There is a need for newer risk predictors of SCD that discriminate the arrhythmic death risk from the non-arrhythmic death risk. In chapter 2and 3 we investigated the relationship between TWA, BVR and infarct size as a quantifier of post MI ventricular remodeling in a pig model and in patients. TWA and BVR were not interrelated and occurred at a different time after MI. BVR was present during early post-MI ventricular remodeling and TWA was detectable in case of a larger myocardial scar late after MI. Infarct size, timing after MI, exercise capacity and beta-blockerintake are all interfering with the outcome of TWA testing and should strictly be controlled in future studies on the predictive value of TWA. In chapter 4 we explored the link between local intracardiac repolarization alternans and body surface TWA through an innovative pacingparadigm. TWA was highly sensitive for picking up subtle repolarization alternans from limited zones of myocardium but did not discriminate between concordant versus discordant local ventricular alternans. This thesis concludes that repolarization variability is an extremely interesting research domain that integrates a multitude of complex pathophysiological mechanisms. This complexity however is a major obstacle for the implementation of these techniques in routine clinical practice. To decide on the real predictive value of these tests, future clinical research should closely monitor the effect of interfering variables and refine the interpretation of test results.status: publishe

From debulking to delivery: sequential use of rotational atherectomy and Guidezilla™ for complex saphenous vein grafts intervention

Percutaneous coronary interventions (PCI) of old calcified saphenous vein grafts (SVGs) is challenging and is associated with a considerably high risk of adverse ischemic events in the short- and long-term as compared to native coronary arteries. We report a case in which a non-dilatable, calcified SVG lesion is successfully treated with rotational atherectomy followed by PCI and stenting with local stent delivery (LSD) technique using the Guidezilla™ guide extension catheter (5-in-6 Fr) in the "child-in-mother" fashion

Incidence of appropriate therapy after replacement of an uneventful first ICD

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Can Body Surface Microvolt T-Wave Alternans Distinguish Concordant and Discordant Intracardiac Alternans?

INTRODUCTION: There is convincing experimental evidence that cellular action potential duration (APD) alternans is arrhythmogenic but its relationship with body surface microvolt T-wave alternans (MTWA) remains unclear. We investigated the relationship between MTWA and APD alternans induced by alternating cycle length (CL) pacing in a pig model. METHODS: In 10 pigs, catheters in the right atrium (RA) and right (RV) and left ventricle (LV) allowed pacing and recording of monophasic action potentials (MAP). During RA pacing at stable 500-ms CL, LV was paced at alternating CL (505 ms and 495 ms). Changing the alternating LV (A-LV) pacing delay changes the size of the region with alternating ventricular activation. Spectral analysis of intracardiac MAP was correlated with body surface MTWA. In a similar setup (during alternating pacing in RV and LV), we investigated concordant versus discordant APD alternans. RESULTS: Pacing the LV with subtle alternating cycle lengths at short A-LV delay leads to broad QRS (97 ± 10 ms), body surface MTWA (mean Valt 4.2 ± 1.8 µV), and positive RR-interval alternans. At longer A-LV delay, not resulting in QRS widening (68 ± 5 ms), body surface RR alternans was absent but MTWA remained detectable and was even more pronounced (8.7 ± 5.1 µV, P < 0.01). During both concordant and discordant pacing MTWA was present. The precordial leads were better for detecting discordant APD alternans (8.0 ± 2.9 µV and 12.8 ± 4.52 µV, P = 0.02). CONCLUSION: MTWA is a potent technique to detect subtle and isolated intracardiac APD alternans that is artificially induced by alternating pacing. In the same model, discordant activation alternans can only be discriminated from concordant when using a quantifying approach of MTWA analysis.status: publishe

The effect of inappropriate ICD therapy on mortality is cause dependent

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The incidence of appropriate therapy after replacement of an uneventful first ICD

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Evolution in ICD implantation an effect on appropriate therapy rates

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The impact of changes in LVEF and renal function on the prognosis of ICD patients after elective device replacement

A proportion of patients with an implantable cardioverter-defibrillator (ICD) in prevention of sudden cardiac death will only receive their first appropriate ICD therapy (AT) after device replacement. Clinical reassessment at the time of replacement could be helpful to guide the decision to replace or not in the future.status: publishe

Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter-Defibrillators Over Time in Ischemic and Dilated Cardiomyopathy Patients

Clinical guidelines on implantable cardioverter-defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality.status: publishe