Andrew R. Kohut

Comprehensive Echocardiographic Assessment of the Right Ventricle in Murine Models

Background Non-invasive high-resolution echocardiography to evaluate cardiovascular function of small animals is increasingly being used due to availability of genetically engineered murine models. Even though guidelines and standard values for humans were revised by the American Society of Echocardiography, evaluations on murine models are not performed according to any standard protocols. These limitations are preventing translation of preclinical evaluations to clinical meaningful conclusions. We have assessed the right heart of two commonly used murine models according to standard clinical guidelines, and provided the practical guide and sample values for cardiac assessments. Methods Right heart echocardiography evaluations of CD1 and C57BL/6 mice were performed under 1–3% isoflurane anesthesia using Vevo® 2100 Imaging System with a high-frequency (18–38 MHz) probe (VisualSonics MS400). We have provided a practical guide on how to image and assess the right heart of a mouse which is frequently used to evaluate development of right heart failure due to pulmonary hypertension. Results Our results show significant differences between CD1 and C57BL/6 mice. Right ventricle structural assessment showed significantly larger (p < 0.05) size, and pulmonary artery diameter in CD1 mice (n = 11) compared to C57BL/6 mice (n = 15). Right heart systolic and diastolic functions were similar for both strains. Conclusion Our practical guide on how to image and assess the right heart of murine models provides the first comprehensive values which can be used for preclinical research studies using echocardiography. Additionally, our results indicate that there is a high variability between mouse species and experimental models should be carefully selected for cardiac evaluations.

Superior vena cava echocardiography as a screening tool to predict cardiovascular implantable electronic device lead fibrosis.

Background Currently there is no noninvasive imaging modality used to risk stratify patients requiring lead extractions. We report the novel use of superior vena cava (SVC) echocardiography to identify lead fibrosis and complex cardiac implantable electronic device (CIED) lead extraction. With an aging population and expanding indications for cardiac device implantation, the ability to deal with the complications associated with chronically implanted device has also increased. Methods This was a retrospective analysis of Doppler echocardiography recorded in our outpatient Electrophysiology/Device Clinic office over 6 months. Images from 109 consecutive patients were reviewed. Results 62% (68/109) did not have a CIED and 38% (41/109) had a CIED. In patients without a CIED, 6% (4/68) displayed turbulent color flow by Doppler in the SVC, while 22% (9/41) of patients with a CIED displayed turbulent flow. Fishers exact test found a statistically significant difference between the two groups (p value < 0.05). The CIED group was subdivided into 2 groups based on device implant duration (< 2 years vs. ≥ 2 years). Of the CIED implanted for ≥ 2 years, 27% (9/33) had turbulent flow in the SVC by Doppler, while no patients (0/8) with implant durations < 2 years demonstrated turbulent flow. Nine patients underwent subsequent lead extraction. A turbulent color pattern successfully identified all 3 patients that had significant fibrosis in the SVC found during extraction. Conclusion Our data suggests that assessing turbulent flow using color Doppler in the SVC may be a valuable noninvasive screening tool prior to lead extraction in predicting complex procedures.

Ultrasound-induced modulation of cardiac rhythm in neonatal rat ventricular cardiomyocytes

Isolated neonatal rat ventricular cardiomyocytes were used to study the influence of ultrasound on the chronotropic response in a tissue culture model. The beat frequency of the cells, varying from 40 to 90 beats/min, was measured based upon the translocation of the nuclear membrane captured by a high-speed camera. Ultrasound pulses (frequency = 2.5 MHz) were delivered at 300-ms intervals [3.33 Hz pulse repetition frequency (PRF)], in turn corresponding to 200 pulses/min. The intensity of acoustic energy and pulse duration were made variable, 0.02-0.87 W/cm(2) and 1-5 ms, respectively. In 57 of 99 trials, there was a noted average increase in beat frequency of 25% with 8-s exposures to ultrasonic pulses. Applied ultrasound energy with a spatial peak time average acoustic intensity (Ispta) of 0.02 W/cm(2) and pulse duration of 1 ms effectively increased the contraction rate of cardiomyocytes (P < 0.05). Of the acoustic power tested, the lowest level of acoustic intensity and shortest pulse duration proved most effective at increasing the electrophysiological responsiveness and beat frequency of cardiomyocytes. Determining the optimal conditions for delivery of ultrasound will be essential to developing new models for understanding mechanoelectrical coupling (MEC) and understanding novel nonelectrical pacing modalities for clinical applications.

The potential of ultrasound in cardiac pacing and rhythm modulation

ABSTRACT Introduction: This review examines the potential for ultrasound to induce or otherwise influence cardiac pacing and rhythm modulation. Areas covered: Of particular interest is the possibility of developing new, truly non-invasive, nonpharmacological, acute and chronic, ultrasound-based arrhythmia treatments. Such approaches would not depend upon implanted or indwelling devices of any kind and would use ultrasound at diagnostic exposure levels (so as not to harm the heart or surrounding tissues). It is known that ultrasound can cause cardiomyocyte depolarization and a variety of underlying mechanisms have been proposed. Expert commentary: Questions still remain regarding the effect of exposure parameters and work will also be necessary to identify the optimal target regions within the heart if ultrasound energy is to be used to induce safe and reliable pacing in a clinical setting.

LOSS OF CHLORIDE INTRACELLULAR CHANNEL PROTEIN 4 PREVENTS CARDIAC HYPERTROPHY IN ISOPROTERENOL INDUCED PRESSURE OVERLOAD IN MOUSE MODELS

Chloride Intracellular Channel Proteins (CLICs) have been implicated in cardiovascular diseases such as pulmonary arterial hypertension and abnormal angiogenesis. However, no studies have explored the direct role of expression of CLICs on cardiac function or the effect of CLIC-dysregulation in

UTILITY OF INTRACARDIAC ECHOCARDIOGRAPHY IN SETTING OF CARDIAC DEVICE-RELATED ENDOCARDITIS AND LEAD EXTRACTION

Transesophageal echocardiography (TEE) is currently the gold standard for diagnosis of cardiac device- related endocarditis (CDE) with a sensitivity of 94-96%. Intracardiac echocardiography (ICE) is routinely used during lead extraction procedures for early identification of procedural complications