A stronger association of diabetes mellitus with impaired hyperaemia using a novel ECG-gated device compared with peripheral arterial tonometry.

PURPOSE: Impaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system. METHODS: In total, 119 controls and 120 participants with diabetes mellitus partook in this cross-sectional study. The EndoPAT2000 system assessed digital reactive hyperaemia under fasting conditions. A mydriatic ECG-gated fundoscope with a novel flicker module acquired digital retinal images of the left eye before, during and after flicker stimulation. An inhouse semi-automated software measured retinal vessel diameters using a validated protocol with two observers repeating measurements in a subset of 10 controls and 10 participants with diabetes mellitus. Intra- and inter-observer reliability analyses occurred by the interclass correlation coefficient. A receiver operating characteristic curve established associations of variables with diabetes mellitus. RESULTS: Diabetes mellitus was more strongly associated with flicker-stimulated retinal arteriolar calibre change from baseline (AUC 0.81, 95% CI 0.75-0.87, p < 0.0001) than reactive hyperaemia index. Median flicker-stimulated arteriolar calibre change from baseline (controls: 2.74%, IQR 1.07 vs diabetes mellitus: 1.64%, IQR 1.25, p < 0.0001) and reactive hyperaemia index (controls: 1.87, IQR 0.81 vs diabetes mellitus: 1.60, IQR 0.81, p = 0.003) were lower in diabetes mellitus than controls. Intra- and inter-observer reliability coefficients were high from 0.87 to 0.93. CONCLUSIONS: Impaired flicker-stimulated retinal arteriolar calibre change from baseline is more highly correlated with diabetes mellitus in this study than a reduced reactive hyperaemia index.

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes.

Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes.Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules.Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88-1.17% vs ECG-gated: 0.39, 95%CI 0.29-0.49%, p < .0001) than venular (ungated 0.62, 95%CI 0.53-0.73% vs ECG-gated: 0.26, 95%CI 0.19-0.35%, p < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively.Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.

Optimizing Impedance Change Measurement During Radiofrequency Ablation Enables More Accurate Characterization of Lesion Formation.

OBJECTIVES: This study sought to determine whether a novel impedance thermal imaging system (ITIS) provides an impedance measurement that is better correlated with lesion dimensions than circuit impedance during radiofrequency (RF) ablation. BACKGROUND: A 5- to 10-Ω impedance drop is clinically used to corroborate an effective RF ablation lesion. However, the contribution of local tissue heating to circuit impedance change is small and dependent on the local environment of the catheter and placement of the grounding patch. METHODS: ITIS uses ablation catheter and skin electrodes to perform 4-terminal impedance measurements with separate voltage sensing and current injection electrode pairs. Seven sheep underwent endocardial ventricular irrigated RF ablation at 40 W for 60 s. ITIS impedance and circuit impedance were both measured throughout ablation. When the sheep were sacrificed, ablation lesions were cut along their long axis; the depth, width, and surface area of the cut surface were measured. RESULTS: A total of 68 RF ablations were performed, with a median depth of 3.5 mm (interquartile range [IQR]: 2.1 to 4.9 mm), width of 8.3 mm (IQR: 5.7 to 10.8 mm), and surface area of 23.8 mm2 (IQR: 9.3 to 43.0 mm2). ITIS impedance change had good correlation with lesion depth, width, and surface area (R = 0.76, R = 0.87, and R = 0.87, respectively); and superior to circuit impedance for lesion depth, width, and surface area (p = 0.0018, p = 0.0004, and p = 0.0001, respectively). CONCLUSIONS: By optimizing the current path and using 4-terminal impedance measurement during RF ablation, the contribution of tissue temperature changes to measured impedance is better standardized to provide a more reliable measure than conventional ablation circuit impedance.

A Novel Microwave Catheter Can Perform Noncontact Circumferential Endocardial Ablation in a Model of Pulmonary Vein Isolation.

INTRODUCTION: Pulmonary vein isolation is an effective treatment for atrial fibrillation. Current endocardial ablation techniques require catheter contact for lesion formation. Inadequate or inconsistent catheter contact results in difficulty with achieving acute and long-term isolation and consequent atrial arrhythmia recurrence. Microwave energy produces radiant heating and therefore can be used for noncontact catheter ablation. We hypothesized that it is possible to design a microwave catheter to produce a circumferential transmural thermal lesion in an in vitro model of a pulmonary vein antrum. METHODS AND RESULTS: A monopole microwave catheter with a sideways firing axially symmetrical heating pattern was designed. Noncontact ablations were performed in a perfused pulmonary vein model constructed from microwave myocardial phantom embedded with a sheet of thermochromic liquid crystal to permit visualization and measurement of thermal lesions from color changes. 1200 J ablations were performed at 150 W for 80 seconds and 120 W for 100 seconds at high (0.8 L/min) and low (0.06 L/min) flow through the modeled pulmonary vein. Myocardial tissue was substituted for the phantom material and ablations repeated at 150 W for 180 seconds and stained with nitro-blue tetrazolium. The catheter was able to induce deep circumferential antral lesions in myocardial phantom and myocardial tissue. Higher power and shorter ablations delivering the same amount of microwave energy resulted in larger lesions with less surface sparing. CONCLUSIONS: A microwave catheter can be designed to produce a circumferential thermal lesion on noncontact ablation and may have possible applications for pulmonary vein isolation.

Acoustic signal emission monitoring as a novel method to predict steam pops during radiofrequency ablation: preliminary observations.

UNLABELLED: Steam pop is an explosive rupture of cardiac tissue caused by tissue overheating above 100 °C, resulting in steam formation, predisposing to serious complications associated with radiofrequency (RF) ablations. However, there are currently no reliable techniques to predict the occurrence of steam pops. We propose the utility of acoustic signals emitted during RF ablation as a novel method to predict steam pop formation and potentially prevent serious complications. METHODS: Radiofrequency generator parameters (power, impedance, and temperature) were temporally recorded during ablations performed in an in vitro bovine myocardial model. The acoustic system consisted of HTI-96-min hydrophone, microphone preamplifier, and sound card connected to a laptop computer. The hydrophone has the frequency range of 2 Hz to 30 kHz and nominal sensitivity in the range -240 to -165 dB. The sound was sampled at 96 kHz with 24-bit resolution. Output signal from the hydrophone was fed into the camera audio input to synchronize the video stream. An automated system was developed for the detection and analysis of acoustic events. RESULTS: Nine steam pops were observed. Three distinct sounds were identified as warning signals, each indicating rapid steam formation and its release from tissue. These sounds had a broad frequency range up to 6 kHz with several spectral peaks around 2-3 kHz. Subjectively, these warning signals were perceived as separate loud clicks, a quick succession of clicks, or continuous squeaking noise. Characteristic acoustic signals were identified preceding 80% of pops occurrence. Six cardiologists were able to identify 65% of acoustic signals accurately preceding the pop. An automated system identified the characteristic warning signals in 85% of cases. The mean time from the first acoustic signal to pop occurrence was 46 ± 20 seconds. The automated system had 72.7% sensitivity and 88.9% specificity for predicting pops. CONCLUSIONS: Easily identifiable characteristic acoustic emissions predictably occur before imminent steam popping during RF ablations. Such acoustic emissions can be carefully monitored during an ablation and may be useful to prevent serious complications during RF delivery.

Electrogram-gated radiofrequency ablations with duty cycle power delivery negate effects of ablation catheter motion.

BACKGROUND: Cardiac and respiratory movements cause catheter instability. Lateral catheter sliding over target endocardial surface can lead to poor tissue contact and unpredictable lesion formation. We describe a novel method of overcoming the effects of lateral catheter sliding movements using an electrogram-gated pulsed power ablation. METHODS AND RESULTS: All ablations were performed on a thermochromic gel myocardial phantom. Ablation settings were randomized to conventional (nongated) 30 W versus electrogram-gated at 20% duty cycle (30 W average power) at 0-, 3-, 6-, and 9-mm lateral sliding distances. Forty-eight radiofrequency ablations were performed. Deeper lesions were created in electrogram-gated versus conventional ablations at 3 mm (4.36±0.08 versus 4.05±0.17 mm; P=0.009), 6 mm (4.39±0.10 versus 3.44±0.15 mm; P<0.001), and 9 mm (4.41±0.06 versus 2.94±0.16 mm; P<<0.001) sliding distances. Electrogram-gated ablations created consistent lesions at a quicker rate of growth in depth when compared with conventional ablations (P<0.001). CONCLUSIONS: (1) Lesion depth decreases and length increases in conventional ablations with greater degrees of lateral catheter movements; (2) electrogram-gated pulsed radiofrequency delivery negated the effects from lateral catheter movement by creating consistently deeper lesions irrespective of the degree of catheter movement; and (3) target lesion depths were reached significantly faster in electrogram-gated than in conventional ablations.

High spatial resolution thermal mapping of radiofrequency ablation lesions using a novel thermochromic liquid crystal myocardial phantom.

BACKGROUND: Radiofrequency (RF) ablation causes thermal mediated irreversible myocardial necrosis. This study aimed to (i) characterize the thermal characteristics of RF ablation lesions with high spatial resolution using a thermochromic liquid crystal (TLC) myocardial phantom; and (ii) compare the thermochromic lesions with in vivo and in vitro ablation lesions. METHODS AND RESULTS: The myocardial phantom was constructed from a vertical sheet of TLC film, with color change between 50 °C (red) to 78 °C (black), embedded within a gel matrix, with impedance titrated to equal that of myocardium. Saline, with impedance titrated to blood values at 37 °C, was used as supernatant. A total of 51 RF ablations were performed. This comprised 17 ablations in the thermochromic gel phantom, bovine myocardial in vitro targets and ovine in vivo ablations, respectively. There was no difference in lesion dimensions between the thermochromic gel and in vivo ablations (lesion width 10.2 ± 0.2 vs 10.2 ± 2.4, P = 0.93; and depth 6.3 ± 0.1 vs 6.5 ± 1.7, P = 0.74). The spatial resolution of the thermochromic film was tested using 2 thermal point-sources that were progressively opposed and was demonstrated to be <300 µm. CONCLUSIONS: High spatial resolution thermal mapping of in vitro RF lesions with spatial resolution of at least 300 µm is possible using a thermochromic liquid crystal myocardial phantom model, with a good correlation to in vivo RF ablations. This model may be useful for assessing the thermal characteristics of RF lesions created using different ablation parameters and catheter technologies.

Automated ventricular substrate mapping--evaluation in an ovine chronic myocardial infarction model.

INTRODUCTION: We hypothesized that automated electrogram analysis might enable rapid localization of ventricular scar. This would allow the delivery of interventions such as radiofrequency ablation or therapeutic agents to critical areas within the scar and scar periphery. METHODS: Substrate mapping was performed on seven sheep 36.5 +/- 32.9 weeks after a left anterior descending artery myocardial infarction had been induced. Contact electrograms and the mapping catheter three-dimensional (3D) location were recorded simultaneously. A computer program was written in-house to automatically identify sinus beats, analyze electrogram characteristics (e.g., electrogram amplitude and minimum slope), and integrate the analysis results into a 3D scar map. RESULTS: The total time required to produce the scar maps was a mean of 8.3 +/- 2.0 minutes. The automated substrate mapping (ASM) system beat detection algorithm had a high sensitivity (i.e., detected 87.4% of the recorded beats) and excellent specificity (only one false activation over 58.2 minutes of total recorded data). The system was able to classify the detected beats ('sinus' or 'ectopic') with high specificity (specificity = 97.3% confidence interval (CI): 96.9-97.7) and moderate sensitivity (sensitivity = 78.3% CI: 77.3%-79.5%). The scar area identified by the ASM system correlated well with the pathologically defined scar area (R2 = 0.87 p < 0.001). CONCLUSIONS: ASM enables accurate scar maps to be produced rapidly. This strategy may play an important role for both clinical and research applications, allowing therapeutic agents and radiofrequency ablation to be delivered to critical locations in and around ventricular scar.

A thermochromic dispersive electrode can measure the underlying skin temperature and prevent burns during radiofrequency ablation.

UNLABELLED: Evaluation of a thermochromic dispersive electrode. INTRODUCTION: Burns at the dispersive electrode are serious complications of diathermy and radiofrequency (RF) ablation procedures. We aimed to create a new methodology to reduce the incidence of dispersive electrode related skin burns. We hypothesized that a dispersive electrode incorporating a thermochromic liquid crystal (TLC) layer could accurately measure underlying skin temperatures and help prevent burns. METHODS AND RESULTS: The TLC electrode was compared with a standard dispersive electrode in 12 male sheep. RF current was delivered with the dispersive electrode fully applied or partially detached to simulate different clinical scenarios. The temperature of the TLC layer, calculated from the hue (color) every 15 seconds, was compared with fluoroptic skin temperature probes. TLC electrodes with a temperature range of 45-58 degrees C were used in six sheep to assess the correlation of TLC temperature distribution with skin temperature and burns. TLC electrodes with a temperature range of 40-50 degrees C were used in another 6 sheep to simulate clinical conditions in which the ablation was stopped if the TLC temperature was >42 degrees C. The TLC measured temperatures correlated well with fluoroptic probes at the skin surface (r=0.94+/-0.05, mean of the absolute difference in temperature difference 0.9+/-0.58 degrees C). Ablations with partial application of standard dispersive electrodes consistently caused skin burns. There were no burns under the TLC electrode when ablations were ceased for temperatures>42 degrees C. CONCLUSIONS: TLC-equipped dispersive electrodes were able to accurately measure skin temperature under the electrode. This technology is likely to prevent dispersive electrode related burns.

Cooled needle catheter ablation creates deeper and wider lesions than irrigated tip catheter ablation.

OBJECTIVES: To design and test a catheter that could create deeper ablation lesions. BACKGROUND: Endocardial radiofrequency (RF) ablation is unable to reliably create transmural ventricular lesions. We designed an intramural needle ablation catheter with an internally cooled 1.1-mm diameter straight needle that could be advanced up to 14 mm into the myocardium. The prototype catheter was compared with an irrigated tip ablation catheter. METHODS: Ablation lesions were created under general anesthesia in 14 male sheep (weight 44 +/- 7.3 kg) with fluoroscopic guidance. Each of the catheters was used to create two ablation lesions at randomly allocated positions within the left ventricle. The irrigation rate, target temperature, and maximum power were: 20 mL/min, 85 degrees C, 50 W for the intramural needle catheter and 20 mL/min, 50 degrees C, 50 W for the irrigated tip catheter, respectively. All ablations were performed for 2 minutes. After the last ablation, blue tetrazolium (12.5 mg/kg) was infused intravenously. The heart was removed via a left thoracotomy after monitoring the sheep for one hour. RESULTS: There was no evidence of cardiac tamponade in any sheep. The intramural needle catheter lesions were significantly wider (10.9 +/- 2.8 mm vs 10.1 +/- 2.4 mm, P = 0.01), deeper (9.6 +/- 2.0 mm vs 7.0 +/- 1.3 mm, P = 0.01), and more likely to be transmural (38% vs 0%, P = 0.03). CONCLUSIONS: Cooled intramural needle ablation creates lesions that are significantly deeper and wider than endocardial RF ablation using an irrigated tip catheter in sheep hearts. This technology may be useful in treating ventricular tachycardia resistant to conventional ablation techniques.