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.

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.

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.

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.

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.

Atrial tachycardias adjacent to the phrenic nerve: recognition, potential problems, and solutions.

BACKGROUND: Ablation of atrial tachycardias (AT) arising from the crista terminalis region (CT) can be complicated by phrenic nerve (PN) injury. OBJECTIVE: This study sought to describe epicardial protection techniques to prevent PN injury from endocardial ablation of AT. METHODS: Ablation was attempted in 4 patients with focal AT arising from the CT in whom conventional endocardial ablation was limited by PN proximity identified by capture during pacing. RESULTS: Four women ages 20, 28, 30, and 31 years with structurally normal hearts presented with symptomatic ATs failing medical therapy. In the first patient, endocardial cryoablation was performed during superior vena cava (SVC) PN pacing. After acute success, AT recurred. Open surgical ablation was then performed, but AT was noninducible under anesthesia, and an anatomic ablation was performed. AT was abolished, but sinus node dysfunction required pacemaker implantation. In the subsequent 3 patients with AT adjacent to the right PN, protection of the PN was attempted by inserting a peripheral angioplasty balloon (2 patients) or steerable ablation catheter and sheath into the epicardial space between the PN and atrium. Endocardial radiofrequency ablation was successful in all 3 patients without PN injury. CONCLUSION: Epicardial protection of the PN allowing for safe endocardial ablation of CT ATs is a feasible method of managing these challenging cases and seems to be preferable to surgery.

Complications of echocardiography-guided endomyocardial biopsy.

A 77-year-old man underwent echocardiography-guided right ventricular endomyocardial biopsy for suspected cardiac amyloidosis. After the procedure, severe tricuspid regurgitation with a flail posterior leaflet was detected. A myocardial biopsy specimen contained a segment of tricuspid valve chorda tendinea. Endomyocardial biopsy is considered the standard for detecting transplant rejection and evaluating infiltrative cardiomyopathies and myocarditis. Echocardiography complements, and in some institutions has replaced, fluoroscopy as a method of bioptome guidance because of its superior resolution of the tricuspid valve anatomy, endocardial surface, and thin right ventricular free wall and apex. Nevertheless, because of the limitations of 2-dimensional imaging, complications do occur.

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 (

Complications of 2-D echocardiography guided transfemoral right ventricular endomyocardial biopsy.

Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac pathologies. However, the routine use of EMBx has not gained widespread acceptance due to the possible complications related to the EMBx. Thus, not much information is available on the complications related to the EMBx. We prospectively evaluated 90 consecutive patients who underwent 2-D echocardiography guided transfemoral right ventricular EMBx at Kyungpook National University Hospital between March 2002 and November 2005 to determine the incidence, nature and subsequent management of complications related to EMBx. The clinical diagnoses before the EMBx were arrhythmogenic right ventricular dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis in 6 and miscellaneous in 2 patients. The overall major complication rate was 5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3), which was the most frequent complication, did not progress to cardiac tamponade requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular tachycardia occurred in 1 patient. New and persistent right bundle branch block occurred in another. Our findings suggest that 2-D echocardiography guided transfemoral right ventricular EMBx is a relatively safe procedure.

Complications of 2-D Echocardiography Guided Transfemoral Right Ventricular Endomyocardial Biopsy

Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac pathologies. However, the routine use of EMBx has not gained widespread acceptance due to the possible complications related to the EMBx. Thus, not much information is available on the complications related to the EMBx. We prospectively evaluated 90 consecutive patients who underwent 2-D echocardiography guided transfemoral right ventricular EMBx at Kyungpook National University Hospital between March 2002 and November 2005 to determine the incidence, nature and subsequent management of complications related to EMBx. The clinical diagnoses before the EMBx were arrhythmogenic right ventricular dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis in 6 and miscellaneous in 2 patients. The overall major complication rate was 5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3), which was the most frequent complication, did not progress to cardiac tamponade requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular tachycardia occurred in 1 patient. New and persistent right bundle branch block occurred in another. Our findings suggest that 2-D echocardiography guided transfemoral right ventricular EMBx is a relatively safe procedure.

Complications of 2-D Echocardiography Guided Transfemoral Right Ventricular Endomyocardial Biopsy

Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac pathologies. However, the routine use of EMBx has not gained widespread acceptance due to the possible complications related to the EMBx. Thus, not much information is available on the complications related to the EMBx. We prospectively evaluated 90 consecutive patients who underwent 2-D echocardiography guided transfemoral right ventricular EMBx at Kyungpook National University Hospital between March 2002 and November 2005 to determine the incidence, nature and subsequent management of complications related to EMBx. The clinical diagnoses before the EMBx were arrhythmogenic right ventricular dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis in 6 and miscellaneous in 2 patients. The overall major complication rate was 5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3), which was the most frequent complication, did not progress to cardiac tamponade requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular tachycardia occurred in 1 patient. New and persistent right bundle branch block occurred in another. Our findings suggest that 2-D echocardiography guided transfemoral right ventricular EMBx is a relatively safe procedure.

[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.

Blunt cardiac trauma caused by fatal falls from height: an autopsy-based assessment of the injury pattern.

BACKGROUND: Falls from height are contributing widely to population morbidity and mortality, especially in urban settings. The presence of blunt cardiac injuries can increase morbidity among these patients, leading even to death. Some clinical studies and case reports have been published on the subject, but a systematic autopsy-based approach to the subject is missing in the literature of recent decades. METHODS: This study reviewed 61 cases of fatal fall from height that were subjected to a full autopsy at the Institute of Legal Medicine, Hamburg, Germany, from 1998 to 2002. The autopsy protocols and available clinical information were evaluated for assessment of the cardiac injury pattern. RESULTS: Cardiac injuries were found in 33 cases (54%), all of which involved falls from heights exceeding 6 m. In 16 cases, the cardiac injuries were the cause of death or contributed to the fatal outcome. In five of these cases, the individuals possibly could have recovered from their trauma if their heart injury had been sufficiently diagnosed and adequately treated in time. The most frequent finding was pericardial tearing (45%). Tears caused by stretching of the epicardium in the area wherein the inferior vena cava leads into the right atrium and epicardial hematoma were present in 11 cases (33%). Endocardial tears of the atria were found in six cases (18%), and did not occur during falls from heights lower than 11 m. Transmural tears to the right atrium were present in 10 cases (39%), and to the left atrium in 6 cases (18%). These tears occurred with increasing frequency in relation to greater heights. When the heights were lower than 15 m, these tears were smaller than 1 cm in diameter, but when the heights exceeded 15 m, extensive irregular tears were observed. Sternal fractures were seen in 76% of all cases involving heart injuries. In 16% of these cases, the fractures were multiple. Only 18% of the cases without cardiac injuries had sternal fractures, and none of these was multiple. Thus, the presence of severe sternal fractures can be used as an indicator of possible cardiac trauma. CONCLUSIONS: A thorough cardiologic diagnosis should always be performed for patients who survive a fall from height. These patients should be transported to a unit capable of performing cardiopulmonary bypass, and explorative thoracotomy should be considered.

Aspectos anátomo-patológicos e histológicos en el corazón de pacientes con endocarditis infecciosa / Anatomopathological and hystological aspects of the heart of patients with infectious endocarditis

Se discute aquellos aspectos anatomopatológicos e histológicos del corazón considerando la patogénesis, bacteremia, patología valvular previa y la morfología de las vegetaciones.

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.