BackgroundMyocardial dysfunction has been implicated in gradual heart failure in transposition of the great arteries (TGA) with a systemic right ventricle (RV). Fibrosis can be assessed using the extracellular volume fraction (ECV). Our aim was to measure ECV and determine its associations with clinical findings and outcomes.MethodsWe prospectively measured ECV in systemic RV subjects (either D-loop after atrial switch or L-loop) and healthy controls. T1 measurements for a single mid-ventricular short-axis plane before and 3, 7, and 15 min after gadolinium contrast were used to quantify systemic ventricular ECV. Individuals with elevated ECV were compared to those without.ResultsIn 53 TGA subjects (age 34.6 ± 10.3 years, 41% female) the mean ECV for the systemic RV (28.7 ± 4.4%) was significantly higher than the left ventricle in 22 controls (26.1 ± 2.8%, P = 0.0104). Those with an elevated ECV (n = 15, 28.3%) had a higher b-type natriuretic peptide (BNP) (P < 0.011) and a longer 6-min walk distance (P = 0.021), but did not differ by age, arrhythmia history, ventricular volume, function, or circulating collagen byproducts. At follow-up (median 4.4 years), those experiencing major cardiovascular endpoints (new arrhythmia, arrhythmia device, heart failure hospitalization, listing for transplantation, mechanical support, or cardiovascular death, n = 14) had a higher ECV. ECV, age, and BNP were independent predictors of cardiac events in Cox-proportional hazard models.ConclusionsMyocardial fibrosis is common in the systemic RV and associated with a higher BNP. Elevated CMR-derived ECV was associated with adverse clinical outcome. The findings suggest a role of diffuse myocardial fibrosis in clinical deterioration of the systemic RV.

We recently investigated left ventricular (LV) myocardial fibrosis using the extracellular volume fraction (LV-ECV) and sought associations with other signs of cardiovascular dysfunction such as systolic dysfunction, exercise intolerance, and arrhythmia to investigate its potential role as a risk

Congenital heart disease with its worldwide incidence of 1% is the most common inborn defect. Increasingly, patients are living into adulthood, with ongoing congenital heart and other medical needs. Sadly, only a small minority have specialist follow-up. However, all patients see their family doctor and may also seek advice from other health professionals. This practical guide with its straightforward a,b,c approach is written for those professionals.

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50%o reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (±1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p <0.05) and 84% (p <0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions. (Circulation Research 1992;70:1137-1145)

Restoring blood flow is the most effective means to limit damage to ischemic tissue. Since the 1960s, surgical placement of bypass grafts for coronary artery disease (CAD) and peripheral vascular disease has effectively and durably restored blood flow to ischemic tissue. Nonsurgical

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine1 and behavioural responses to stress2, and the related hormone urocortin3 (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2 (refs 4,5). These receptors may exhibit distinct functions due to unique tissue distribution6 and pharmacology4,5. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses7,8. Here we generate Crhr2−/− mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2−/− mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2−/− mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2–/– mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2−/− mice following Ucn, but Crhr2−/− mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2−/− mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2−/− mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

EchogenTM, a phase shift, fluorocarbon gas echo contrast agent, has been shown capable of producing left ventricular and robust myocardial opacification, persisting up to 35 to 40 mm after peripheral venous injection. We investigated the microcirculatory flow dynamics of this agent in the cat mesenteric vascular bed using microscopic visualization of capillary flows. Four cats (weight 2 to 5.2 kg, mean = 3.2 kg) were anesthetized and ventilated. Systemic arterial blood pressure was monitored by cannulation of the carotid artery. Microscopic examination (x 400) with an instrument calibrated for scale was performed by placing a loop of small intestine on awarm water bath stage and transilluminating the mesentery with a xenon light source while videotape recording the images for off-line analysis. Transthoracic echocardiography was performed simultaneously using a TOSHIBA 140A system with a 7 MHz transducer. Doses of 0.4, 06, 0.8 ml/kg (a total of 15 injections) of Echogen were administered intravenously. For all the injections, Visually apparent left ventricular and intense myocardial opacification was achieved lasting up to 20 minutes. A transient drop in arterial blood pressure (25 ± 13.2 mmHg) was observed with the high dose 10.8 ml/kg). which returned to baseline within 5 mins. Capillary flow velocities of the red blood cells before and after Echogen injection were 4.3 ± 1.7 mm/sec dropping to 2.3 ± 0.9 mm/sec, the drop occurred 5 to 20 seconds following injections and recovery was within 40–70 seconds. Transient slowing and periodicity of flow was noted in the venule side of the capillaries. but arteriolar capillary flow changed little during brisk transit of the observed bubbles. There was no significant difference in flow velocity changes associated with different doses (p > 0.05). Also, margination and endothelial adhesion of bubbles observed in larger arteriolar feeding vessels without slowing of central RBC flow suggests a mechanism for the long persistence of echo contrast bubbles in the tissue without vascular blockage or evidence of myocardial tissue damage.

The availability of new contrast agents capable of transpulmonary, left ventricular and myocardial opacification after intravenous injection warrants evaluation of their efficacy for assessing abnormalities of myocardium perfusion and results of intervention. In the present study, open chest epicardial echocardiography (7 MHz) was performed during intravenous administration of MRX 115, a new lipid contrast agent at a dose of 0.02 or 0.05 ml/kg in 6 instrumented monkeys before and after acute LAD ligation and following reperfusion. Visually apparent myocardial opacification was evident in all animals for all IV injections of MRX before LAD occlusion without significant hemodynamic effect. After LAD occlusion, a "filling defect" overlapping the area with abnormal wall motion could be delineated and uptake of subsequently injected contrast could be demonstrated within 10 to 20 minutes following release of LAD occlusion. The peak videodensitometric (VD) changes (256 unit scale) from baseline after IV. MRX injection over each of 6 areas of coronary perfusion areas on the LV short axis before and after LAD occlusion and 20 minutes following release are shown (mean ± SE):Empty CellPre-OcclusionPost-OcclusionReperfusion1. Anteroseptal46.65 ± 7.011.87 ± 2.17*44.17 ± 3.992. Anterior32.48 ± 12.600.04 ± 5.01*34.37 ± 4.983. Lateral15.12 ± 4.3926.29 ± 8.435.52 ± 9.154. Posterolateral12.13 ± 3.7713.43 ± 5.9514.79 ± 4.555. Inferior23.59 ± 4.6220.80 ± 9.257.58 ± 7.026. Posteroseptal45.21 ± 11.0519.56 ± 5.0518.02 ± 4.10*p < 0.001 p < 0.001 As the data showed, after LAD occlusion anteroseptal (1) and anterolateral (2) segments showed a statistically significant loss (* p < 0.001) of their preocclusion contrast echo VD change and it was recovered following reperfusion. In our study, MRX provided visual and VD delineation of myocardium at risk and changes induced by reperfusion after IV injection.

A rare entity that causes congenital mitral regurgitation is an isolated cleft mitral valve. The cleft in the mitral valve can be seen in either the anterior or posterior leaflet of the valve. We present a unique case of an individual with a history of congenital mitral regurgitation caused by a cleft in both the anterior and posterior leaflets of the mitral valve.

Preliminary reporting of echocardiographic data by cardiac sonographers has become a key issue in the echocardiography community. A survey on this issue was sent to 248 academic physicians and 89 (35.8%) were returned. In response to a question in the survey, 76 physicians stated that they had at least a limited amount of knowledge in echocardiography. For the group, 62% wanted a written or verbal preliminary report and 52% concluded that this report should be a part of the cardiac sonographer's position. If cardiac abnormalities are suspected, 65% wanted the results before the cardiologist reviewed the study, but only 42% of the physicians wanted a diagnostic versus a descriptive type of report. About 49% stated that if necessary they would attempt to influence the cardiac sonographer to give them a preliminary report, whereas 67% of the physicians would possibly use this information to medically manage the patient. Fifty percent believed that it was legal for a cardiac sonographer to give a preliminary report. Another 70% said that the cardiac sonographer would NOT be "practicing medicine without a license" and 66% concluded that they would NOT be "aiding and abetting the unauthorized practice of medicine" if given this information. These data have important potential ramifications for both cardiac sonographers as well as for the practice of cardiology regarding the issue of preliminary echocardiographic reports.

The donor interatrial septa of 46 heart transplant recipients were measured from 4 serial echocardiograms. The purpose of the study was to determine the thickness of the donor interatrial septum and to assess whether changes in the septal thickness occur over time, either with ischemic duration at the time of surgery or with the number of treated rejection episodes during the first year after transplant. This study showed that the donor interatrial septum has increased thickness after heart transplantation but returns to normal by the 12 months after transplant. However, there was no correlation with the number of treated rejection episodes or ischemic time.