Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

Cardiovascular Rehabilitation With a WCD-Data From the CR3 Study (Cardiac Rehab Retrospective Review).

PURPOSE: Patients at risk for sudden cardiac death may temporarily need a wearable cardioverter-defibrillator (WCD). Exercise-based cardiac rehabilitation (CR) has a class I recommendation in patients with cardiac disease. The aim of this study was to evaluate the safety and feasibility of undergoing CR with a WCD. METHODS: We performed a retrospective analysis of all patients with a WCD who completed a CR in Austria (2010-2020). RESULTS: Patients (n = 55, 60 ± 11 yr, 16% female) with a median baseline left ventricular ejection fraction (LVEF) of 36 (30, 41)% at the start of CR showed a daily WCD wearing duration of 23.4 (22, 24) hr. There were 2848 (8 [1, 26]/patient) automatic alarms and 340 (3 [1, 7]/patient) manual alarms generated. No shocks were delivered by the WCD during the CR period. One patient had recurrent hemodynamically tolerated ventricular tachycardias that were controlled with antiarrhythmic drugs.No severe WCD-associated adverse events occurred during the CR stay of a median 28 (28, 28) d. The fabric garment and the device setting needed to be adjusted in two patients to diminish inappropriate automatic alarms. Left ventricular ejection fraction after CR increased significantly to 42 (30, 44)% ( P < .001). Wearable cardioverter-defibrillator therapy was stopped due to LVEF restitution in 53% of patients. In 36% of patients an implantable cardioverter-defibrillator was implanted, 6% had LVEF improvement after coronary revascularization, one patient received a heart transplantation (2%), two patients discontinued WCD treatment at their own request (4%). CONCLUSION: Completing CR is feasible and safe for WCD patients and may contribute positively to the restitution of cardiac function.

CoolLoop® First: A First In Man Study To Test A Novel Circular Cryoablation System In Paroxysmal Atrial Fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation is the mainstay of catheter treatment of paroxysmal atrial fibrillation (AF). The CoolLoop® cryoablation catheter (AFreeze® GmbH; Innsbruck, Austria) was developed to create wide and complete circular lesions around the PVs. In this study we evaluated feasibility and safety of this novel ablation system in humans. METHODS: 10 patients (6M/4F; 57.6±7.6y) with paroxysmal AF were included in 2 referral centers. The CoolLoop® catheter was positioned at each PV antrum using a steerable transseptal sheath. Subsequently, 2-6 double-freezes over 5min were performed at each vein and PV-isolation was assessed thereafter using a circular mapping catheter. During cryoablation of the right PVs, pacing was used to monitor phrenic nerve function. RESULTS: The CoolLoop® catheter could be successfully positioned at each PV. A mean of 5.6±1.8 cryoablations were performed in the LSPV, 5.2±1.6 in the LIPV, 6.3±2.5 in the RSPV and 5.4±1.6 in the RIPV, respectively. Mean procedure time was 251±60min and mean fluoroscopy time was 44.0±13.2min. 6 / 10 LSPV, 6 / 10 LIPV, 5 / 10 RSPV and 6 / 10 RIPV could be isolated exclusively using the novel cryoablation system. One patient developed groin hematoma and a brief episode of ST-elevation due to air embolism was observed in another subject. No other clinical complications occurred during 3 months of follow up. CONCLUSIONS: PV-isolation for paroxysmal atrial fibrillation using the CoolLoop® catheter is feasible and appears safe. Clinical long term efficacy still needs to be evaluated and will be compared with established catheters used for AF ablation.

Non-invasive imaging of cardiac electrophysiology in a cardiac resynchronization therapy defibrillator patient with a quadripolar left ventricular lead.

AIMS: The present study was aimed to assess epi- and endocardial ventricular electroanatomical activation during cardiac resynchronization therapy (CRT) by means of non-invasive imaging of cardiac electrophysiology (NICE) in a patient with a novel quadripolar LV lead. METHODS AND RESULTS: Non-invasive imaging of cardiac electrophysiology is a novel imaging tool which works by fusing data from high-resolution electrocardiogram (ECG) mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. This was performed in a cardiac resynchronization therapy defribrillator (CRT-D) patient with a quadripolar left ventricular (LV) lead. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed using NICE during intrinsic conduction as well as during different pacing modes with different LV and biventricular (biV) pacing vectors. The spatial resolution of NICE enabled discrimination of the different pacing vectors during LV and biV pacing. Biventricular pacing resulted in a marked shortening of the total activation duration (TAD) of both ventricles when compared with intrinsic conduction and RV and LV pacing. CONCLUSION: Non-invasive imaging of cardiac electrophysiology facilitates non-invasive imaging of ventricular activation, which may be useful in CRT patients to locate the area of latest ventricular activation as the target area for LV lead placement. Moreover, especially in non-responders to CRT NICE may be further useful to determine the best electrical repositioning option.

Single-beat noninvasive imaging of ventricular endocardial and epicardial activation in patients undergoing CRT.

BACKGROUND: Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation. METHODOLOGY/PRINCIPAL FINDINGS: NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group). NICE is a fusion of data from high-resolution ECG mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed during native rhythm as well as during ventricular pacing using a bidomain theory-based heart model to solve the related inverse problem. During right ventricular (RV) pacing control patients showed a deterioration of the ventricular activation sequence similar to the intrinsic activation pattern of CHF patients. Left ventricular propagation velocities were significantly decreased in CHF patients as compared to the control group (1.6±0.4 versus 2.1±0.5 m/sec; p<0.05). CHF patients showed right-to-left septal activation with the latest activation epicardially in the lateral wall of the left ventricle. Biventricular pacing resulted in a resynchronization of the ventricular activation sequence and in a marked decrease of total LV activation duration as compared to intrinsic conduction and RV pacing (129±16 versus 157±28 and 173±25 ms; both p<0.05). CONCLUSIONS/SIGNIFICANCE: Endocardial and epicardial ventricular activation can be visualized noninvasively by NICE. Identification of individual ventricular activation properties may help identify responders to CRT and to further improve response to CRT by facilitating a patient-specific lead placement and device programming.

Impact of oxygen uptake efficiency slope as a marker of cardiorespiratory reserve on response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is limited by the high numbers of nonresponders. This study analyzed the impact of the cardiorespiratory functional reserve to predict the response to CRT. METHODS AND RESULTS: Twenty-eight patients (age 67 ± 9 years, LVEF < 35%, NYHA class III, QRS 158 ± 25 ms) underwent submaximal cardiopulmonary treadmill exercise testing prior and 6 months after implantation of a CRT device. Breath-to-breath gas analysis was used for calculation of the oxygen uptake efficiency slope (OUES = non-effort-dependent index of cardiorespiratory functional reserve) in the responder and nonresponder group. Responders to CRT [defined by a decrease in left ventricular end-systolic volume (LVESV) > 15%] showed a significant lower cardiorespiratory reserve at baseline (prior CRT) as compared to the nonresponders (OUES 1,235 ± 651 vs. 2,480 ± 590; p < 0.01). Responders showed an increase in OUES during CRT at the 6 months follow-up (1,879 ± 663; p < 0.05) whereas nonresponders showed no significant changes from baseline (2,194 ± 422; ns). Both responders and nonresponders showed an improvement in LVEF at the 6 months follow-up (23 ± 5 vs. 31 ± 9% and 26 ± 7 vs. 32 ± 3%; p < 0.05). Responders to CRT showed a decrease in NYHA classification (3.0 vs. 2.6 ± 0.5; p < 0.05) and a decrease in LVESV (175 ± 58 vs. 128 ± 40 ml; p < 0.05). CONCLUSIONS: Nonresponders to CRT showed a more preserved cardiorespiratory functional reserve as compared to responders despite similar NYHA classification. Evaluation of the OUES by submaximal exercise testing improves identification of responders to CRT.

Single-beat noninvasive imaging of cardiac electrophysiology of ventricular pre-excitation.

OBJECTIVES: The aim of this study was to determine whether noninvasive imaging of cardiac electrophysiology (NICE) is feasible in patients with Wolff-Parkinson-White (WPW) syndrome in the clinical setting of a catheter laboratory and to test the accuracy of the noninvasively obtained ventricular activation sequences as compared with that of standard invasive electroanatomic mapping. BACKGROUND: NICE of ventricular activation could serve as a useful tool in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. METHODS: NICE works by fusing the data from high-resolution electrocardiographic mapping and a model of the patient's cardiac anatomy obtained by magnetic resonance imaging. The ventricular activation sequence was computed with a bidomain theory-based heart model to solve this inverse problem. Noninvasive imaging of cardiac electrophysiology was performed in 7 patients with WPW syndrome undergoing catheter ablation of the accessory pathway. The position error of NICE was defined as the distance between the site of earliest activation computed by NICE and the successful ablation site identified by electroanatomic mapping (CARTO; Biosense Webster, Diamond Bar, California) for normal atrioventricular (AV) conduction as well as for adenosine-induced AV block. RESULTS: The error introduced by geometric coupling of the CARTO data and the NICE model was 5 +/- 3 mm (model discretization 10 mm). All ventricular accessory pathway insertion sites were identified with an accuracy of 18.7 +/- 5.8 mm (baseline) and 18.7 +/- 6.4 mm (adenosine). CONCLUSIONS: The individual cardiac anatomy model obtained for each patient enables accurate noninvasive electrocardiographic imaging of ventricular pre-excitation in patients with WPW syndrome. Noninvasive imaging of cardiac electrophysiology might be used as a complementary noninvasive approach to localize the origin and help identify and understand the underlying mechanisms of cardiac arrhythmias.

Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial.

BACKGROUND: Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide. CONCLUSIONS: Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women.

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). METHODS: In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. RESULTS: During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. CONCLUSIONS: Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.

Homocysteine impairs coronary microvascular dilator function in humans.

OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND: Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known. METHODS: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously). RESULTS: Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05). CONCLUSION: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.