Development of a novel shock wave catheter ablation system-A validation study in pigs in vivo.

Aims: Although the radiofrequency catheter ablation (RFCA) is widely used for the treatment of tachyarrhythmias, it has three fundamental weaknesses as a thermal ablation system, including a limited lesion depth, myoendocardial injury linking to thromboembolism, and prolonged inflammation followed by subsequent recurrences. In order to overcome these limitations, we have been developing a shock wave (SW) catheter ablation (SWCA) system as a novel non-thermal therapy. In the present study, we validated our new SWCA system with increased SW intensity. Methods and results: In a total of 36 pigs, we applied our new SWCA to ventricular muscle in vivo for the following protocols. (i) Epicardial approach (n = 17): The lesion depth achieved by the SWCA from the epicardium was examined. High intensity SW achieved 5.2 ± 0.9 mm lesions (35 applications), where there was a strong correlation between SW intensity and lesion depth (R = 0.80, P < 0.001, 54 applications). (ii) Endocardial approach (n = 6): The extent of endocardial injury with the two energy sources was examined by electron microscopy (8 applications each). Shock wave catheter ablation markedly reduced myoendothelial injury compared with RFCA (4.3 ± 1.2 vs. 79.6 ± 4.8%, P < 0.01). The electrophysiological effects on the SW lesions were also confirmed using three-dimensional mapping system. (iii) Time-course study (n = 6 each): The healing process after ablation therapy was examined. We found transient inflammatory responses and accelerated reparative process with preserved blood flow in the SWCA group. Conclusion: These results indicate that our SWCA system is characterized, as compared with RFCA, by deeper lesion depth, markedly less myoendocardial injury and accelerated tissue repair process.

Nitinol wire mesh fracture and traumatic left atrial thrombus in a patient with atrial septal defect amplatzer occluder.

Although wire device frame fracture associated with thrombus formation has been reported in some types of atrial septal defect occluders, it has not been detected in patients with Amplatzer devices. Here, we describe an unusual case of Nitinol wire mesh fracture associated with left atrial endocardial damage and thrombus formation in an adult with Amplatzer septal occluder.

Relationship between catheter forces, lesion characteristics, "popping," and char formation: experience with robotic navigation system.

INTRODUCTION: Popping, char and perforation are complications that can occur following catheter ablation. We measured the amount of grams (g) applied to the endocardium during ablation using a sensor incorporated in the long sheath of a robotic system. We evaluated the relationship between lesion formation, pressure, and the development of complications. METHODS: Using a robotic navigation system, lesions were placed in the left atrium (LA) at six settings, using a constant duration (40 seconds) and flow rate of either 17 cc/min or 30 cc/min with an open irrigated catheter (OIC). Evidence of complications was noted and lesion location recorded for later analysis at necropsy. RESULTS: Lesions using 30 Watts (W) were more likely to be transmural at higher (>40 g) than lower (<30 g) pressures (75% vs 25%, P < 0.001). Significantly higher number of lesions using >40 g of pressure demonstrated "popping" and crater formation as compared with lesions with 20-30 g of pressure (41% vs 15%, P = 0.008). A majority of lesions placed using higher power (45 W) with higher pressures (>40 g) were associated with char and crater formation (66.7%). No lesions using 10 g of pressure were transmural, regardless of the power. Lesions placed with a power setting less than 35 W were more likely to result in "relative" sparing of the endocardial surface than lesions at a power setting higher than 35 W (62% vs 33.3%, P = 0.02) regardless of the pressure. CONCLUSIONS: When using an OIC, lower power settings (

Characterization of Myocardial Microstructure and Function in an Experimental Model of Isolated Subendocardial Damage.

Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.

Exploring the cardiac response to injury in heart transplant biopsies.

BACKGROUND: Because injury is universal in organ transplantation, heart transplant endomyocardial biopsies present an opportunity to explore response to injury in heart parenchyma. Histology has limited ability to assess injury, potentially confusing it with rejection, whereas molecular changes have potential to distinguish injury from rejection. Building on previous studies of transcripts associated with T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), we explored transcripts reflecting injury. METHODS: Microarray data from 889 prospectively collected endomyocardial biopsies from 454 transplant recipients at 14 centers were subjected to unsupervised principal component analysis and archetypal analysis to detect variation not explained by rejection. The resulting principal component and archetype scores were then examined for their transcript, transcript set, and pathway associations and compared to the histology diagnoses and left ventricular function. RESULTS: Rejection was reflected by principal components PC1 and PC2, and by archetype scores S2TCMR, and S3ABMR, with S1normal indicating normalness. PC3 and a new archetype score, S4injury, identified unexplained variation correlating with expression of transcripts inducible in injury models, many expressed in macrophages and associated with inflammation in pathway analysis. S4injury scores were high in recent transplants, reflecting donation-implantation injury, and both S4injury and S2TCMR were associated with reduced left ventricular ejection fraction. CONCLUSION: Assessment of injury is necessary for accurate estimates of rejection and for understanding heart transplant phenotypes. Biopsies with molecular injury but no molecular rejection were often misdiagnosed rejection by histology.TRAIL REGISTRATION. ClinicalTrials.gov NCT02670408FUNDING. Roche Organ Transplant Research Foundation, the University of Alberta Hospital Foundation, and Alberta Health Services.

Endocardial photoablation by excimer laser.

A xenon-chlorine excimer laser was used to irradiate normal endocardium of fresh sheep and pig hearts as well as unfixed human endocardial scar. Forty pulses of 370 J and 35 ns each resulted in penetration of up to 12 mm in normal tissue and only 3.5 mm in scarred endocardium. Dosimetry indicated that the volume of vaporized scarred tissue was 1/10th that of normal endocardium (0.19 to 0.40 versus 1.35 to 3.22 mm3/J). Ultrastructurally, there was a sharp demarcation of only 10 mu between the region of injury and normal myocardium, with little evidence of heat injury. The high power and short duration of these lasers coupled with the lack of a boundary zone of injury suggest that excimers may be an ideal tool for arrhythmia ablation.

[Pathomorphology of the endocardium and myocardium in the heart injury].

Light, polarization, luminescent microscopy, phase contrast, special staining methods and scanning electron microscopy were used for studying sections and fragments of the endocardium and myocardium from 123 patients who had died of heart contusion and ischemic heart disease and from 50 rats with experimental heart contusion. The morphological classification of heart contusion and differential-diagnostic table of myocardial alterations due to contusion of the heart and ischemic heart disease are proposed to facilitate pathomorphological diagnosis of heart contusion. The classification of pathomorphological signs in heart contusion is presented.

Right pneumothorax resulting from an endocardial screw-in atrial lead.

Right pneumothorax complicated by an endocardial atrial lead has never been reported. Herein, we report on a small-build 79-year-old Taiwanese woman who suffered from complete AV block and underwent dual-chamber permanent pacemaker implantation. An active fixation screw-in atrial lead was chosen. The procedure was complicated by right pneumothorax associated with atrial perforation. Since simple measurements of the implantation parameters could not be used to predict the occurrence of perforation, great caution should be taken in to avoid overscrewing the atrial lead, and in scrutinizing the penetration depth of the helix of the lead under fluoroscopy.

Posttraumatic left ventricular pseudoaneurysm due to intramyocardial dissecting hematoma.

A left ventricular aneurysm can develop in patients sustaining blunt chest injury. This condition has been attributed to myocardial contusion or to a direct vascular lesion leading to myocardial necrosis. We report the case of a pseudoaneurysm resulting from myocardial dissection beginning from a small tear in the endocardial wall. Successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure of the communications between the aneurysm and the left ventricular cavity is described.

Systemic release of thrombomodulin, but not from the cardioplegic, reperfused heart during open heart surgery.

Thrombomodulin is a potential marker of endothelial injury. Plasma thrombomodulin was measured in concomitant arterial and coronary sinus samples in 9 patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB, 88 +/- 14 min) (mean +/- SD) and cold, crystalloid, antegrade cardioplegia (44 +/- 14 min). Arterial thrombomodulin was 17 +/- 6 ng/ml before surgery, and decreased to 10 +/- 5 ng/ml after heparinization (p < 0.008 compared to initial value). During CPB thrombomodulin increased, with a maximal level of 23 +/- 7 ng/ml (p < 0.008 vs initial value) 40 min after aortic declamping. No difference between arterial and coronary sinus concentrations was detected during reperfusion of the heart. In conclusion, plasma thrombomodulin is decreased by heparin, and increased during CPB. Consequently, thrombomodulin may be used to evaluate endothelial injury during CPB. However, as there is no specific intracoronary release of thrombomodulin during reperfusion, thrombomodulin is not a suitable marker of coronary endothelial injury after cardioplegia.

Differentiation between transmural perioperative myocardial infarction and subendocardial injury after coronary artery bypass grafting using biochemical tests, elaborated by cluster and discriminant analysis.

The aim of this study is to differentiate between transmural perioperative myocardial infarction (T-PMI) and subendocardial perioperative myocardial injury (S-PMI) as a complication of coronary artery bypass grafting (CABG). Seventy-three patients undergoing CABG were followed post operatively by measuring troponin T, CK-MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha hydroxybutyrate dehydrogenase (HBD), and aspartate aminotransferase (AST) at five sampling times. Lacking a proper definition of the gold standard for the diagnosis of perioperative myocardial infarction, a statistical procedure was used. Supported by the cluster analysis method of Ward, patients were assigned to a patient group with a perioperative myocardial infarction (PMI) or a patient group without a PMI (non-PMI) as a confirmation of interpretation of the biochemical results. Using the results of electrocardiogram (ECG) and echocardiography, the PMI patient group was split into a T-PMI patient group and a S-PMI patient group. With discriminant analysis, two canonic discriminant functions were drawn up to differentiate between patients suffering from a T-PMI or S-PMI and non-PMI patients.

Successful management of osteal perforation of left anterior descending artery with coated stent.

Coronary perforation is a rare complication of percutaneous coronary intervention. We report a case of left anterior descending artery osteal perforation that led to acute cardiac tamponade during excimer laser angioplasty. Perforation was successfully covered with a PTFE-coated stent with preserved distal coronary flow.

Development of an endocardioscope for repair of an atrial septal defect in the beating heart.

The purpose of this study was to evaluate the possibility of surgical treatment of an atrial septal defect in the beating heart without cardiopulmonary bypass. The first step was to develop an endocardioscope that permitted observation of the inside of the beating heart. To visualize the inside of the beating heart, the tip of the endoscope was covered with a glass adapter. The endocardioscope was inserted through the right atrial appendage in eight beagles. The atrial septum, foramen ovale, coronary sinus, tricuspid valve, and chordae tendineae were identified without hemodynamic derangement. The second step was to attempt to close the foramen ovale with clips or staplers. We were able to close the foramen ovale with these devices, but a safer, easier device is needed. The endocardioscope we developed should prove to be a useful tool for minimally invasive surgical treatment of heart diseases, such as atrial septal defect.

[Hazards and complications of temporary endocardial stimulation]. / Opasnosti i oslozhneniia vremennoi endokardial'noi stimuliatsii.

In conducting 381 stimulations in 330 patients with brady- and tachysystolic disorders of cardiac rhythm of various etiology 122 complications were revealed. Dislocation of the electrode was noted in 71 cases (18.6%), perforation of the myocardium by the endocardial electrode in 9 (2.1%), ventricular fibrillation in 11 (2.3%), and sepsis in 5 (1.3%) of the cases. A special device may be used for the immediate detection of dislocation. Characteristic changes are noted on the intracardiac ECG in penetration of the electrode into the myocardium (precursor of perforation).

Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.

Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within 3 hr of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoic acid (RA)-synthesizing enzyme raldh2. By one day posttrauma, raldh2 expression becomes localized to endocardial cells at the injury site, an area that is supplemented with raldh2-expressing epicardial cells as cardiogenesis begins. Induced transgenic inhibition of RA receptors or expression of an RA-degrading enzyme blocked regenerative cardiomyocyte proliferation. Injured hearts of the ancient fish Polypterus senegalus also induced and maintained robust endocardial and epicardial raldh2 expression coincident with cardiomyocyte proliferation, whereas poorly regenerative infarcted murine hearts did not. Our findings reveal that the endocardium is a dynamic, injury-responsive source of RA in zebrafish, and indicate key roles for endocardial and epicardial cells in targeting RA synthesis to damaged heart tissue and promoting cardiomyocyte proliferation.

Temperature-controlled cooled-tip radiofrequency ablation in left ventricular myocardium.

Steam pop and intramural charring have been reported during cooled-tip radiofrequency catheter ablation (RFCA). We studied the feasibility of temperature-controlled cooled-tip RFCA in the canine heart.An internally cooled ablation catheter was inserted into the left ventricle. A custom-made radiofrequency (RF) generator capable of controlling the tip-temperature at the preset level by slow increases in the power was used. Temperature-controlled cooled-tip RF applications were performed at a target temperature of 40 degrees C for 90 seconds. Acute study: Intramyocardial temperature was measured at the ablation site in 10 dogs by inserting a fluoroptic probe. Chronic study: Lesion depth and volume were measured in 5 dogs after 3 weeks of survival. In the acute study, no pop or abrupt impedance rise was observed. Maximum intramyocardial temperature was 72.4 + or - 14.4 degrees C at 2-4 mm above the endocardium. No coagulum formation, craters, or intramural charring were observed. Maximum lesion depth was 6.7 + or - 1.5 mm, and lesion volume was 404 + or - 219 mm3. In the chronic study, maximum lesion depth was 5.9 + or - 1.1 mm, and lesion volume was 281 + or - 210 mm(3).Temperature controlled RFCA is feasible with a cooled-tip catheter and an RF generator that slowly increases the RF power until the preset catheter-tip temperature is reached.