Cost-Effectiveness of Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation in the Australian Health Care System.

BACKGROUND: Heart transplantation is an effective treatment for end-stage congestive heart failure, however, achieving the right balance of immunosuppression to maintain graft function while minimising adverse effects is challenging. Serial endomyocardial biopsies (EMBs) are currently the standard for rejection surveillance, despite being invasive. Replacing EMB-based surveillance with cardiac magnetic resonance (CMR)-based surveillance for acute cardiac allograft rejection has shown feasibility. This study aimed to assess the cost-effectiveness of CMR-based surveillance in the first year after heart transplantation. METHOD: A prospective clinical trial was conducted with 40 orthotopic heart transplant (OHT) recipients. Participants were randomly allocated into two surveillance groups: EMB-based, and CMR-based. The trial included economic evaluations, comparing the frequency and cost of surveillance modalities in relation to quality-adjusted life years (QALYs) within the first year post-transplantation. Sensitivity analysis encompassed modelled data from observed EMB and CMR arms, integrating two hypothetical models of expedited CMR-based surveillance. RESULTS: In the CMR cohort, 238 CMR scans and 15 EMBs were conducted, versus (vs) 235 EMBs in the EMB group. CMR surveillance yielded comparable rejection rates (CMR 74 vs EMB 94 events, p=0.10) and did not increase hospitalisation risk (CMR 32 vs EMB 46 events, p=0.031). It significantly reduced the necessity for invasive EMBs by 94%, lowered costs by an average of AUD$32,878.61, and enhanced cumulative QALY by 0.588 compared with EMB. Sensitivity analysis showed that increased surveillance with expedited CMR Models 1 and 2 were more cost-effective than EMB (all p<0.01), with CMR Model 1 achieving the greatest cost savings (AUD$34,091.12±AUD$23,271.86 less) and utility increase (+0.62±1.49 QALYs, p=0.011), signifying an optimal cost-utility ratio. Model 2 showed comparable utility to the base CMR model (p=0.900) while offering the benefit of heightened surveillance frequency during periods of elevated rejection risk. CONCLUSIONS: CMR-based rejection surveillance in orthotopic heart transplant recipients provides a cost-effective alternative to EMB-based surveillance. Furthermore, it reduces the need for invasive procedures, without increased risk of rejection or hospitalisation for patients, and can be incorporated economically for expedited surveillance. These findings have important implications for improving patient care and optimising resource allocation in post-transplant management.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Metabolic Sequelae of Everolimus Treatment After Cardiac Transplant: A Hypothesis-Generating Study.

BACKGROUND: Although modern immunosuppressants improve survival post-transplant, they are associated with long-term metabolic complications, such as post-transplant diabetes mellitus (PTDM). Calcineurin inhibitor-sparing regimens using everolimus attenuate some complications such as left ventricular hypertrophy. However, the metabolic effects of everolimus following transplant are less clear. METHODS: Post-hoc analysis to compare PTDM and other metabolic outcomes in participants of a randomised open-label clinical trial of low-dose everolimus and tacrolimus versus standard-dose tacrolimus in heart transplant recipients (RADTAC1 study). RESULTS: There were 39 participants in the trial; mean follow-up was 6.4±1.5 years. There was a high rate of pre-existing diabetes (26%) and newly diagnosed PTDM (36%) during follow-up. Half the patients who developed PTDM in the everolimus-tacrolimus group (n=4/8) ceased diabetes medications during follow-up, which was not observed in patients on standard tacrolimus (n=0/6). In the first 12 months there was a higher use of non-insulin treatment for diabetes in the everolimus-tacrolimus group compared to the standard tacrolimus group. CONCLUSIONS: This study suggests that treatment with everolimus may be associated with improved glycaemic control of PTDM relative to treatment with standard doses of calcineurin inhibitor. These findings should be further studied in prospective randomised trials.

Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials. METHODS: Four days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 106 cells were injected at three sites within the infarcted left ventricular (LV) wall. RESULTS: One month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits. CONCLUSIONS: The authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an "off-the-shelf" stem cell therapy for cardiac repair.

Renal Artery Denervation in Resistant Hypertension: The Good, The Bad and The Future.

Early studies of renal artery denervation (RAD) demonstrated efficacy in treating resistant hypertension patients with significant reduction in office blood pressure (BP). This resulted in a growing enthusiasm in the field and a rapid evolution of technology with expanding procedural indications. However, the first randomised sham-controlled trial, Symplicity HTN-3, failed to demonstrate a significant difference in BP reduction between the RAD and the sham control arm, which subsequently led to a major reduction in the clinical application of this procedure. Additionally, the results generated further interest into understanding the mechanism and factors affecting procedural success and identifying the limitations within the field. Many lessons were learned from Symplicity HTN-3 trial, and with recent evidence emerging for RAD in hypertension treatment, the field continues to be refined.

Influence of Body Mass Index on Recurrence of Ventricular Arrhythmia, Mortality in Defibrillator Recipients With Ischaemic Cardiomyopathy.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. There is little known, however, about the influence of body mass index (BMI) on spontaneously occurring ventricular arrhythmias in patients with ischaemic heart disease. We sought to examine the effect of BMI on the ventricular arrhythmia (VA) recurrence and mortality in defibrillator recipients with ischaemic cardiomyopathy. METHODS: Consecutive patients (n = 123) with ischaemic cardiomyopathy (left ventricular ejection fraction (LVEF) ≤ 40%) and a primary or secondary prevention defibrillator were included. Patients were classified according to their BMI as being normal (18.5-24.99, n = 54/ 43.9%), overweight (2 -29.99, n = 43/ 35%) or obese (>30, n = 26/20.3%). RESULTS: The primary combined endpoint of VA recurrence and mortality occurred in 36%, 5.4% and 11.5% of patients with normal, overweight and obese BMI (p = 0.001). When adjusting for risk factors such as ejection fraction, age and triple vessel disease, on multivariable analysis, normal BMI remained a significant predictor for the primary outcome (Hazard Ratio, Normal vs Overweight = 7.1, 95% CI 1.8-25, p = 0.002: Hazard Ratio, Normal vs Obese = 5.5, 95% CI 1.11-25, p = 0.033). There was a non-significant trend towards reduced survival in patients with normal weight in comparison to overweight and obese patients (p = 0.08). CONCLUSION: In defibrillator recipients with ischaemic cardiomyopathy, BMI appears to be a significant predictor for the combined primary outcome of spontaneously occurring ventricular arrhythmias and mortality. Normal BMI, compared to overweight and obese patients had worse outcomes, suggesting the presence of the obesity paradox in ventricular arrhythmogenesis late post infarction.

Renal Artery Branch Denervation: Evaluation of Lesion Characteristics Using a Thermochromic Liquid Crystal Phantom Model.

BACKGROUND: Lately, combined main vessel and branch ablation has been recommended during radiofrequency (RF) renal artery denervation. Utilising a validated renal artery phantom model, we aimed (1) to determine thermal injury extent (lesion depth, width and circumferential coverage) and electrode-tissue interface temperature for branch renal artery ablation, and (2) to compare the extent of thermal injury for branch versus main vessel ablation using the same RF System. METHODS: We employed a gel based renal artery phantom model simulating variable vessel diameter and flow, which incorporated a temperature sensitive thermochromic-liquid-crystal (TLC) film for assessing RF ablation thermodynamics. Ablations in a branch renal artery model (n = 32) were performed using Symplicity Spyral (Medtronic, Minneapolis, MN, USA). Lesion dimensions defined by the 51 °C isotherm, circumferential injury coverage, and electrode-tissue interface temperature were measured for all ablations at 60 seconds. RESULTS: Lesion dimensions were 2.13 ± 0.13 mm and 4.13 ± 0.18 mm for depth and width, respectively, involving 23% of the vessel circumference. Maximum electrode-tissue interface temperature was 68.31 ± 2.29 °C. No significant difference in lesion depth between branch and main vessel ablations was found (Δ = 0.02 mm, p = 0.60). However, lesions were wider in the branch (Δ=0.49 mm, p < 0.001) with a larger circumferential coverage compared to main vessel (arc angle of 82.02±3.27° versus 54.90±4.36°, respectively). CONCLUSIONS: In the phantom model, branch ablations were of similar depth but had larger width and circumferential coverage compared to main vessel ablations. Concerning safety, no overheating at the electrode-tissue interface was observed.

Analysis of recombinant adeno-associated viral vector shedding in sheep following intracoronary delivery.

Differences between mouse and human hearts pose a significant limitation to the value of small animal models when predicting vector behavior following recombinant adeno-associated viral (rAAV) vector-mediated cardiac gene therapy. Hence, sheep have been adopted as a preclinical animal, as they better model the anatomy and cardiac physiological processes of humans. There is, however, no comprehensive data on the shedding profile of rAAV in sheep following intracoronary delivery, so as to understand biosafety risks in future preclinical and clinical applications. In this study, sheep received intracoronary delivery of rAAV serotypes 2/6 (2 × 1012 vg), 2/8, and 2/9 (1 × 1013 vg) at doses previously administered in preclinical and clinical trials. This was followed by assessment over 96 h to examine vector shedding in urine, feces, nasal mucus, and saliva samples. Vector genomes were detected via real-time quantitative PCR in urine and feces up to 48 and 72 h post vector delivery, respectively. Of these results, functional vector particles were only detected via a highly sensitive infectious replication assay in feces samples up to 48 h following vector delivery. We conclude that rAAV-mediated gene transfer into sheep hearts results in low-grade shedding of non-functional vector particles for all excreta samples, except in the case of feces, where functional vector particles are present up to 48 h following vector delivery. These results may be used to inform containment and decontamination guidelines for large animal dealings, and to understand the biosafety risks associated with future preclinical and clinical uses of rAAV.

Comparison of two different radiofrequency ablation systems for renal artery denervation: Evaluation of short-term and long-term follow up.

OBJECTIVES: To assess the clinical efficacy of renal artery denervation (RAD) in our center and to compare the efficacy of two different radiofrequency (RF) systems. BACKGROUND: Several systems are available for RF renal denervation. Whether there is a difference in clinical efficacy among various systems remains unknown. METHODS: Renal artery denervation was performed on 43 patients with resistant hypertension using either the single electrode Symplicity Flex (n = 20) or the multi-electrode EnligHTN system (n = 23). Median post-procedural follow-up was 32.93 months. The primary outcome was post-procedural change in office blood pressure (BP) within 1 year (short-term follow-up). Secondary outcomes were change in office BP between 1 and 4 years (long-term follow-up) and the difference in office BP reduction between the two systems at each follow-up period. RESULTS: For the total cohort, mean baseline office BP (systolic/diastolic) was 174/94 mmHg. At follow-up, mean changes in office BP from baseline were -19.70/-11.86 mmHg (P < 0.001) and -21.90/-13.94 mmHg (P < 0.001) for short-term and long-term follow-up, respectively. The differences in office BP reduction between Symplicity and EnligHTN groups were 8.96/1.23 mmHg (P = 0.42 for systolic BP, P = 0.83 for diastolic BP) and 9.56/7.68 mmHg (P = 0.14 for systolic BP, P = 0.07 for diastolic BP) for short-term and long-term follow-up, respectively. CONCLUSIONS: In our cohort, there was a clinically significant office BP reduction after RAD, which persisted up to 4 years. No significant difference in office BP reduction between the two systems was found.

Human Connexin40 Mutations Slow Conduction and Increase Propensity for Atrial Fibrillation.

BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS: Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene). Electrophysiology studies (EPS) were performed just prior to and 7 days after surgery. Left atria were assessed for connexin expression, mRNA levels, inflammation and fibrosis. Primary cardiomyocyte cultures were also transduced with the abovementioned vectors (n=6 per transgene) and monolayer conduction velocities (CV) and protein expression were assessed at 96hours. RESULTS: At day 7 EPS, P wave and induced atrial fibrillation (AF) durations were significantly longer in the mutant groups when compared to wtCx40 controls (p<0.05). There were no significant differences in inflammation, fibrosis, or heart to body weight ratios. Monolayer CV's were reduced in the A96S group compared to the wtCx40 group. While similar to wtCx40 controls, P88S velocities were reduced compared to eGFP controls. G38D monolayers possessed spontaneous fibrillatory activity and could not be paced. Immunofluorescence revealed that P88S and G38D reduced native connexin43 myocyte coupling while A96S appeared to co-localise with connexin43 in gap junctions. Connexin43 mRNA levels were similar between groups. CONCLUSIONS: The A96S, G38D, and P88S Cx40 mutations slow conduction and increased the propensity for inducible AF.

Five seconds of 50-60 W radio frequency atrial ablations were transmural and safe: an in vitro mechanistic assessment and force-controlled in vivo validation.

AIMS: Longer procedural time is associated with complications in radiofrequency atrial fibrillation ablation. We sought to reduce ablation time and thereby potentially reduce complications. The aim was to compare the dimensions and complications of 40 W/30 s setting to that of high-power ablations (50-80 W) for 5 s in the in vitro and in vivo models. METHODS AND RESULTS: In vitro ablations-40 W/30 s were compared with 40-80 W powers for 5 s. In vivo ablations-40 W/30 s were compared with 50-80 W powers for 5 s. All in vivo ablations were performed with 10 g contact force and 30 mL/min irrigation rate. Steam pops and depth of lung lesions identified post-mortem were noted as complications. A total of 72 lesions on the non-trabeculated part of right atrium were performed in 10 Ovine. All in vitro ablations except for the 40 W/5 s setting achieved the critical lesion depth of 2 mm. For in vivo ablations, all lesions were transmural, and the lesion depths for the settings of 40 W/30 s, 50 W/5 s, 60 W/5 s, 70 W/5 s, and 80 W/5 s were 2.2 ± 0.5, 2.3 ± 0.5, 2.1 ± 0.4, 2.0 ± 0.3, and 2.3 ± 0.7 mm, respectively. The lesion depths of short-duration ablations were similar to that of the conventional ablation. Steam pops occurred in the ablation settings of 40 W/30 s and 80 W/5 s in 8 and 11% of ablations, respectively. Complications were absent in short-duration ablations of 50 and 60 W. CONCLUSION: High-power, short-duration atrial ablation was as safe and effective as the conventional ablation. Compared with the conventional 40 W/30 s setting, 50 and 60 W ablation for 5 s achieved transmurality and had fewer complications.

Ninety Seconds Could be the Optimal Duration for Ventricular Radiofrequency Ablation - Results From a Myocardial Phantom Model.

BACKGROUND: Shallow lesions could be the predominant factor affecting the efficacy of ventricular radiofrequency (RF) ablations. The objective of this study was to assess lesion dimensions and overheating in extended RF ablations up to 180seconds and compare with that of conventional 30seconds ablations. METHODS: The Navistar Thermocool irrigated catheter (Biosense Webster, CA, USA) was used in a previously validated myocardial phantom. Ablations were performed with 20W, 30W, 40W and 50W powers for 180seconds. The volume of lesion and overheating were measured at 530C and 800C isotherms respectively. RESULTS: A total of 110 RF lesions were analysed. The lesion depth increment when ablation was extended from the conventional 30seconds to 90seconds were 31.2±0.2, 33.6±0.6, 36.3±1.8% of that at 30seconds, respectively for powers 30W, 40W and 50W. During 30W ablations, at 90seconds the lesion width and depth were 95.4±1.2%, 91.8±1.6% respectively of the final dimensions at 180seconds. Similar proportions were observed for 40W and 50W. During 40W ablations, the volume of overheating was 113±6% and 184±11% higher at 90seconds and 180seconds respectively compared to that at 30seconds and was 142±9% and 194±9% for 50W ablations. CONCLUSION: Extending RF ablations up to 90seconds significantly increased the lesion depth (30-40%), however, overheating was present at 40W and 50W powers. Ablations beyond 90seconds provided little incremental value.

Circuit Impedance Could Be a Crucial Factor Influencing Radiofrequency Ablation Efficacy and Safety: A Myocardial Phantom Study of the Problem and its Correction.

BACKGROUND: Circuit impedance could affect the safety and efficacy of radiofrequency (RF) ablation. AIM: To perform irrigated RF ablations with graded impedance to compare (1) lesion dimensions and overheated dimensions in fixed power ablations (2) and in power corrected ablations. METHODS: Ablations were performed with irrigated Navistar Thermocool catheter and Stockert EP shuttle generator at settings of 40 W power for 60 seconds, in a previously validated myocardial phantom. The impedance of the circuit was set at 60 Ω, 80 Ω, 100 Ω, 120 Ω, 140 Ω, and 160 Ω. The lesion and overheated dimensions were measured at 53 °C and 80 °C isotherms, respectively. In the second set of ablations, power was corrected according to circuit impedance. RESULTS: In total, 70 ablations were performed. The lesion volume was 72.0 ± 4.8% and 44.7 ± 4.6% higher at 80 Ω and 100 Ω, respectively, compared to that at 120 Ω and it was 15.4 ± 1.2%, 28.1 ± 2.0%, and 38.0 ± 1.8% lower at 140 Ω, 160 Ω, and 180 Ω, respectively. The overheated volume was four times larger when impedance was reduced to 80 Ω from 100 Ω. It was absent at 120 Ω and above. In the power corrected ablations, the lesion volumes were similar to that of 40 W/120 Ω ablations and there was no evidence of overheating. CONCLUSION: The lesion and overheated dimensions were significantly larger with lower circuit impedance during irrigated RF ablation and the lesion size was smaller in high impedance ablations. Power delivery adjusted to impedance using a simple equation improved the consistency of lesion formation and prevented overheating.

Observations on Attenuation of Local Electrogram Amplitude and Circuit Impedance During Atrial Radiofrequency Ablation: An In vivo Investigation Using a Novel Direct Endocardial Visualization Catheter.

AIMS: To define the temporal characteristics of atrial lesion growth (lesion surface area), local electrogram amplitude attenuation, and circuit impedance decrement during in vivo radiofrequency (RF) ablation with direct endocardial visualization (DEV). METHODS AND RESULTS: A direct endocardial visualization catheter was used for real-time endoscopic visualization of atrial endocardial surface during RF ablation. Videos of lesion growth (surface area), circuit impedance, and local electrogram amplitude were recorded during ablation in 11 ovine. Fifty-two atrial ablations at 12 W, 14 W, and 16 W power for 30 seconds were analyzed. During 30-second RF ablation, the lesion matured (90% of final lesion dimension) in the first 23.0 ± 5.8 seconds. The local electrogram amplitude attenuation (80% decrement) and circuit impedance attenuation (20% decrement from initial) occurred 13.8 ± 8.2 seconds and 13.1 ± 7.9 seconds, respectively, before lesion maturity in a significant proportion of 30 second atrial ablations. CONCLUSION: The DEV observations suggest that in smooth atrial surface ablations with significant local electrogram and impedance decrement in the first 10 seconds, further extension of ablation for 10-15 seconds could deliver optimal surface dimensions; however, real-time measurement of depth was not possible.

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.

Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia.

BACKGROUND: Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. METHODS AND RESULTS: Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). CONCLUSIONS: Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.

Intra-cardiac motion detection catheter for the early identification of acute pericardial tamponade during invasive cardiac procedures.

Objectives: To develop and test an intra-cardiac catheter fitted with accelerometers to detect acute pericardial effusion prior to the onset of hemodynamic compromise. Background: Early detection of an evolving pericardial effusion is critical in ensuring timely treatment. We hypothesized that the reduction in movement of the lateral heart border present in developing pericardial effusions could be quantified by positioning an accelerometer in a lateral cardiac structure. Methods: A "motion detection" catheter was created by implanting a 3-axis accelerometer at the distal tip of a cardiac catheter. The pericardial space of 5 adult sheep was percutaneously accessed, and pericardial tamponade was created by infusion of normal saline. The motion detection catheter was positioned in the coronary sinus. Intracardiac echocardiography was used to confirm successful creation of pericardial effusion and hemodynamic parameters were collected. Results: Statistically significant reduction in acceleration from baseline was detected after infusion of only 40 ml of normal saline (p < 0.05, ANOVA). In comparison, clinically significant change in systolic blood pressure (defined as >10% drop in baseline systolic blood pressure) occurred after infusion of 80 ml of normal saline (107 ± 22 mmHg vs. 90 ± 12 mmHg p = 0.97, ANOVA), and statistically significant change was recorded only after infusion of 200 ml (107 ± 22 mmHg vs. 64 ± 5 mmHg, p < 0.05, ANOVA). Conclusions: An intra-cardiac motion detection catheter is highly sensitive in identifying acute cardiac tamponade prior to clinically and statistically significant changes in systolic blood pressure, allowing for early detection and treatment of this potentially life-threatening complication of all modern percutaneous cardiac interventions.

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.

Atrial cardiomyopathy: Current and future imaging methods for assessment of atrial structure and function.

Changes in atrial size and function have historically been considered a surrogate marker of ventricular dysfunction. However, it is now recognized that atrial cardiomyopathy (ACM) may also occur as a primary myocardial disorder. Emerging evidence that ACM is a major risk factor for atrial fibrillation, heart failure, and thromboembolic stroke, has highlighted the significance of this disorder and the need for better assessment of atrial metrics in clinical practice. Key barriers in this regard include a lack of standardized criteria or hierarchy for the diagnosis of ACM and lack of consensus for the most accurate phenotyping methods. In this article we review existing literature on ACM, with a focus on current and future non-invasive imaging methods for detecting abnormalities of atrial structure and function. We discuss the relative advantages and disadvantages of transthoracic echocardiography and cardiac magnetic resonance imaging for assessing a range of parameters, including atrial size and contractile function, strain, tissue characteristics, and epicardial adipose tissue. We will also present the potential application of novel imaging methods such as sphericity index and four- or five-dimensional flow.

In vivo evaluation of virtual electrode mapping and ablation utilizing a direct endocardial visualization ablation catheter.

BACKGROUND: Radiofrequency (RF) ablation utilizing direct endocardial visualization (DEV) requires a "virtual electrode" to deliver RF energy while preserving visualization. This study aimed to: (1) examine the virtual electrode RF ablation efficacy; (2) determine the optimal power and duration settings; and (3) evaluate the utility of virtual electrode unipolar electrograms. METHODS AND RESULTS: The DEV catheter lesions were compared to lesions formed using a 3.5 mm open irrigated tip catheter within the right atria of 12 sheep. Generator power settings for DEV were titrated from 12W, 14W and 16W for 20, 30 and 40 seconds duration with 25 mL/min saline irrigation. Standard irrigated tip catheter settings of 30W, 50°C for 30 seconds and 30 mL/min were used. The DEV lesions were significantly greater in surface area and both major and minor axes compared to irrigated tip lesions (surface area 19.43 ± 9.09 vs 10.88 ± 4.72 mm, P<0.01) with no difference in transmurality (93/94 vs 46/47) or depth (1.86 ± 0.75 vs 1.85 ± 0.57 mm). Absolute electrogram amplitude reduction was greater for DEV lesions (1.89 ± 1.31 vs 1.49 ± 0.78 mV, P = 0.04), but no difference in percentage reduction. Pre-ablation pacing thresholds were not different between DEV (0.79 ± 0.36 mA) and irrigated tip (0.73 ± 0.25 mA) lesions. There were no complications noted during ablation with either catheter. CONCLUSIONS: Virtual electrode ablation consistently created wider lesions at lower power compared to irrigated tip ablation. Virtual electrode electrograms showed a comparable pacing and sensing efficacy in detecting local myocardial electrophysiological changes.