Determination of single cryoablation outcome within 30 to 60 seconds of freezing based on ice impedance.

BACKGROUND: A direct indicator of effective pulmonary vein isolation (PVI) based on early ice formation is presently lacking. OBJECTIVE: The initial impedance rise within 30 to 60 seconds (sec) of single cryoablation relating to ice on the distal surface of the cryoballoon could; predict effective PVI with early termination, the need for prolonging the cryoablation, or failure to achieve effective ablation. METHODS: Impedance measurements were taken between two ring electrodes, at the anterior balloon surface and at the shaft behind the balloon. Ice covering the anterior ring leads to impedance rise. Single cryoablation (eight animals, 37 veins) was applied for 90 to 180 sec. Cryoapplication was terminated if the impedance reached ≥500 Ω. Impedance levels at ≤60 sec of cryoablation were divided into three groups based on the characteristics of the impedance rise. PVI was confirmed acutely and at 45 ± 9 days recovery by electrophysiology mapping and histopathology. RESULTS: At 60 sec of freezing, an impedance rise of 34.1 ± 15.2 Ω (13-50 Ω) and slope of the impedance rise (measured during 15-30 sec of cryoapplication) less than 1 Ω/sec resulted in failed PVI. An impedance rise of 104.4 ± 31.5 Ω (76-159 Ω) and slope of 2 Ω/sec resulted in 100% PVIs. An impedance rise of 130.9 ± 137.8 Ω (40-590 Ω) and slope of 10 Ω/sec resulted in 100% PVIs with early termination at 90 sec. CONCLUSION: The efficacy of single cryoablation can be defined within 30 to 60 sec based on ice impedance. Three unique impedance profiles described in this investigation are associated with the uniformity and thickness of the ice buildup on the anterior surface of the balloon. One cryoablation with an adequate impedance rise is needed for successful outcomes.

Phytochemicals from Achillea fragrantissima are Modulators of AßPP Metabolism.

Plant derivatives offer a novel and natural source of therapeutics. The desert plant Achillea fragrantissima (Forssk) Sch. Bip (Af) is characterized by protective antioxidative and anti-inflammatory properties. Here, we examined the effect of two Af-derived phytochemicals on learning and memory, amyloid-ß protein precursor (AßPP) metabolism, and tau phosphorylation in the familial Alzheimer's disease-linked APPswe/PS1ΔE9 mouse model. We observed that mice that were injected with the phytochemicals showed a trend of improvement, albeit statistically insignificant, in the Novel Object Recognition task. However, we did not observe improvement in contextual fear conditioning, suggesting that the benefits of treatment may be either indirect or task-specific. In addition, we observed an increase in the full-length form of AßPP in the brains of mice treated with Af-derived phytochemicals. Interestingly, both in vivo and in vitro, there was no change in levels of soluble Aß, oligomeric Aß, or the carboxyl terminus fragments of AßPP (APP-CTFs), suggesting that the increase in full length AßPP does not exacerbate AßPP pathology, but may stabilize the full-length form of the molecule. Together, our data suggest that phytochemicals present in Af may have a modest positive impact on the progression of Alzheimer's disease.

Characteristics of Ice Impedance Recorded From a Ring Electrode Placed at the Anterior Surface of the Cryoballoon: Novel Approach to Define Ice Formation and Pulmonary Vein Isolation.

BACKGROUND: The success of cryoablation of the pulmonary vein isolation (PVI) is dependent on transmural and circumferential ice formation. We hypothesize that rising impedance recorded from a ring electrode placed 2 mm from the cryoballoon signifies ice formation covering the balloon surface and indicates ice expansion. The impedance level enables titration of the cryoapplication time to avoid extracardiac damage while ensuring PVI. METHODS AND RESULTS: In 12 canines, a total of 57 pulmonary veins were targeted for isolation. Two cryoapplications were delivered per vein with a minimum of 90 and maximum of 180-second duration. Cryoapplication was terminated on reaching a 500 Ω change from baseline. Animals recovered 38±6 days post-procedure, and veins were assessed electrically for isolation. Heart tissue was histologically analyzed. Extracardiac structures were examined for damage. PVI was achieved in 100% of the veins if the impedance reached 500 Ω in <90 seconds with freeze time of 90 seconds. When 500 Ω was reached >90 to 180 seconds (142.60±29.3 seconds), 90% PVI was achieved. When the final impedance was between 200 and 500 Ω with 180 seconds of freeze time, PVI was achieved in 86.8%. For impedance of <200 Ω, PVI was achieved in 14%. No extracardiac damage was recorded. CONCLUSIONS: Impedance rise of 500 Ω at <90 seconds with freeze time of 90 seconds resulted in 100% PVI. Impedance measurements from the nose of the balloon is a direct measure of ice formation on the balloon. It provides real-time feedback on the quality of the ablation and defines the cryoapplication termination time based on ice formation, limiting ice expansion to extracardiac tissues.

Novel dyeless and fluoro-less approach to cryoballoon pulmonary vein occlusion assessment.

BACKGROUND: Pulmonary vein (PV) occlusion is essential for PV isolation (PVI) using the cryoballoon. Currently occlusion is arbitrarily determined using fluoroscopy and contrast media. This study aimed to create an objective measure without utilizing excessive fluoroscopy and using no contrast media. OBJECTIVE: To ensure PV occlusion without fluoroscopy and contrast dye. METHODS: In 4 in vivo hearts 113 PV occlusions were tested with a 50% cold dye saline mix at 4°C. Occlusions were rated Good, Fair, and Poor by dye dissipation seen via fluoroscopy and correlated to temperature profiles recorded concurrently. Using these temperature profiles and no dye, cryoablations were placed in 12 additional hearts (56 unique veins, 126 occlusions). Two 180-second cryoablation applications were placed per vein with occlusion testing in between. PVI was defined by electrophysiology mapping, gross pathology, and histology after ≥4 weeks recovery. RESULTS: Dye results were as follows: With Good, Fair, and Poor the maximal postinjection PV temperature dropped (ΔT) by 6.2 ± 4.2°C, 5.1 ± 3.7°C, and 2.4 ± 2.0°C. At 5 seconds post nadir temperature, injection temperature recovered 18% ± 14%, 36% ± 23%, and 50% ± 33%. Console thaw time to 0°C was 11.5 ± 4.8 seconds, 8.5 ± 2.1 seconds, and 4.3 ± 1.3 seconds. Success rate for PVI was 100%, 97%, and 0%. With no dye: ΔT: 7.7 ± 4.4°C, 5.8 ± 5.0°C, and 3.4 ± 2.3°C; % recovery at 5 seconds: 15% ± 12%, 31% ± 23%, 45% ± 30%; thaw time to 0°C: 11.9 ± 4.8 seconds, 10.5 ± 5.2 seconds, 6.0 ± 2.8 seconds; success rate: 97%, 91%, and 10%. CONCLUSION: PV occlusion profile determination using 4°C cold saline injection is an effective approach to define the occlusion grade. Quality occlusions correlate strongly with PVI success.

Relationship between lesion formation and electrophysiological responses using catheters equipped with mini-electrodes in chronic atrial fibrillation.

BACKGROUND: The study focuses on the electrophysiological changes associated with lesion formation using 4.5-mm irrigated and 8-mm standard catheters equipped with mini-electrodes (MEs) positioned circumferentially on the tip. OBJECTIVE: The aim of the study was to test the relationship between the maximal electrogram (EGM) reduction, frequency spectrum shift, and their impact on atrial lesion formation in the atrial fibrillation (AF) model. Furthermore, we hypothesize that the high fidelity recording from the MEs allows improved discrimination of ablated tissues from nonablated tissues. METHODS: Under fluoroscopic and NavX guidance, atrial ablation lesions were placed in 4 canines in chronic AF (>12 months in AF) to achieve intercaval, cavotricuspid isthmus, and left atrial contiguous lesions. Lesion times were titrated to the maximal loss of EGM amplitude as recorded from the MEs. Radiofrequency (RF) lesions were sequentially connected on the basis of the ME recordings of tissue viability. RESULTS: In lesions formed using a 4.5-mm irrigated catheter (172 lesions) and in those formed using an 8-mm catheter (155 lesions), the time to nadir of the EGM reduction was 22 ± 12 and 22 ± 9 seconds (NS:p>0.05). Contiguous transmural lesions were successfully placed and guided by the ME EGMs and confirmed by frequency spectra. CONCLUSION: In the chronic AF model, EGM reduction and frequency spectrum shift recorded from the MEs are twice the reduction recorded using the 4.5mm and 8mm tip to ring electrodes. RF titration based on the maximal EGM diminution is an effective approach to monitor lesion formation and may improve safety by preventing unnecessarily prolonged RF application. The ME EGM recording greatly facilitates placement of contiguous transmural linear lesions.

Cryotherapy of cardiac arrhythmia: From basic science to the bedside.

This review focuses on the basic science of cellular destruction by tissue freezing and application of transvenous cryocatheter technology to treat cardiac arrhythmia. Ideally, foci for arrhythmias are selectively ablated, arrhythmogenic tissues are destroyed, and reentry circuits are bisected in order to silence adverse electrical activity, with the goal of restoring normal sinus rhythm. The mechanism of ablation using cryotherapy results in distinct lesion qualities advantageous to radiofrequency (Khairy P, Chauvet M, Lehman J, et al. Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 2003;107:2045-2050). This review is devoted to the mechanism of cryoablation, postablation histopathological changes, and how this information should be used by the clinicians to improve safety and maximize ablation success.

Maximal electrogram attenuation recorded from mini electrodes embedded on 4.5-mm irrigated and 8-mm nonirrigated catheters signifies lesion maturation.

BACKGROUND: The electrograms (EGMs) recorded from mini electrodes (ME) placed on the tip of the ablation electrode allow more precise EGM monitoring during lesion formation. Our objective was to define the lesion boundaries and extracardiac injuries resulting from 60-second RF application versus RF application time titrated to maximal attenuation of the ME EGM in the atria and ventricles using 4.5-mm irrigated and 8-mm catheters. METHODS: RF lesions were placed in both atria and ventricles in 13 (30-35 kg) canines; 6 (4.5-mm OI) and 7 (8 mm). The RF application time was fixed at 60 seconds or terminated at maximal ME EGM amplitude attenuation. RESULTS: Pre/postablation pacing thresholds, EGM amplitudes, and lesion dimensions were not significantly different between maximal EGM attenuation and 60-second RF application using either catheter. Atrial lesion transmurality was also similar for both catheters and groups 91.2% (4.5 mm) and 96% (8 mm) when the RF was titrated to the maximal EGM attenuation and 94.2% (4.5 mm) and 95% (8 mm) with 60-second RF. The 60-second RF ablation, however, presented with significant extracardiac injuries to the lungs and esophagus, along with char formation. Deep ventricular lesions were noted with maximal EGM attenuation that were not different from the 60-second RF ablation. CONCLUSION: Titration of the RF application time to the maximal EGM attenuation based on the ME recordings represents atrial lesion maturation and deep ventricular lesions. Prolonging the RF application results in greater extracardiac injury and char formation without increasing lesion size.