Prevalence of left atrial appendage thrombus detected by transoesophageal echocardiography before catheter ablation of atrial fibrillation in patients anticoagulated with non-vitamin K antagonist oral anticoagulants.

AIMS: There is ongoing controversy about the need for routine transoesophageal echocardiography (TOE) prior to atrial fibrillation (AF) ablation. Recently, the debate was reignited by the publication of a large series of patients showing a prevalence of left atrial appendage thrombus (LAAT) on TOE of 4.4%. We sought to assess the prevalence of LAAT on TOE before AF ablation at our institution. METHODS AND RESULTS: Consecutive patients scheduled for AF ablation at our institution between January 2009 and December 2016 were included. All patients were on oral anticoagulation for at least 4 weeks prior to TOE. Transoesophageal echocardiographies were performed 3-5 days prior to scheduled AF ablation. Data were collected utilizing a prospective database. In all, 668 patients and 943 AF ablation procedures were included. Mean age was 64 ± 11 years, 72% were male, average CHADS2 score was 1.0 ± 1.0, and 72% of the patients had paroxysmal AF. At the time of ablation, 496 (53%) were on non-vitamin K antagonist oral anticoagulants (NOACs) and 447 (47%) were on Warfarin. There were three cases with LAAT (3/943, 0.3%), all of whom had persistent AF and were on Warfarin. Two patients underwent surgical ablation and the third patient did not undergo ablation. CONCLUSION: In our experience, the prevalence of LAAT in patients on anticoagulation therapy undergoing TOE before catheter ablation of AF is 0.3%, which was much lower than recently reported. None of the patients with paroxysmal AF or on NOACs were found to have LAAT. Rather than routine use of TOE prior to AF ablation, a risk-based approach should be considered.

Randomized Trial Comparing the Effects of Ticagrelor Versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease.

BACKGROUND: Ticagrelor is a P2Y12 receptor inhibitor used in acute coronary syndromes to reduce platelet activity and to decrease thrombus formation. Ticagrelor is associated with a reduction in mortality incremental to that observed with clopidogrel, potentially related to its non-antiplatelet effects. Evidence from animal models indicates that ticagrelor potentiates adenosine-induced myocardial blood flow (MBF) increases. We investigated MBF at rest and during adenosine-induced hyperemia in patients with stable coronary artery disease treated with ticagrelor versus clopidogrel. METHODS AND RESULTS: This randomized double-blinded crossover study included 22 patients who received therapeutic interventions of ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 10 days between the treatments. Global and regional MBF and myocardial flow reserve were measured using rubidium 82 positron emission tomography/computed tomography at baseline and during intermediate- and high-dose adenosine. Global MBF was significantly greater with ticagrelor versus clopidogrel (1.28±0.55 versus 1.13±0.47 mL/min per gram, P=0.002) at intermediate-dose adenosine and not different at baseline (0.65±0.19 versus 0.60±0.15 mL/min per gram, P=0.084) and at high-dose adenosine (1.64±0.40 versus 1.61±0.19 mL/min per gram, P=0.53). In regions with impaired myocardial flow reserve (<2.5), MBF was greater with ticagrelor compared with clopidogrel during intermediate and high doses of adenosine (P<0.0001), whereas the differences were not significant at baseline. CONCLUSIONS: Ticagrelor potentiates global and regional adenosine-induced MBF increases in patients with stable coronary artery disease. This effect may contribute to the incremental mortality benefit compared with clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01894789.

An unusual case of cardiogenic shock: common cause from uncommon etiology.

Mechanical complications of an acute coronary syndrome can lead to hemodynamic instability out of proportion to the degree of left ventricular dysfunction. We present the case of a patient with cardiogenic shock secondary to severe mitral regurgitation in the setting of an acutely occluded obtuse marginal artery. Echocardiography and pathologic findings revealed an uncommon cause of anterolateral papillary muscle rupture. Using the unique features of this case, we present a clinical self-assessment exercise highlighting the challenges involved in the management of this type of patient.

Preclinical evaluation of biopolymer-delivered circulating angiogenic cells in a swine model of hibernating myocardium.

BACKGROUND: Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. METHODS AND RESULTS: Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery. After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion results. Arteriole density and wall motion abnormalities improved in the cells+matrix group. There was also a strong trend toward an improvement in ejection fraction (P=0.07). CONCLUSIONS: In this preclinical swine model of ischemic and hibernating myocardium, the combined delivery of circulating angiogenic cells and a collagen-based matrix restored perfusion, reduced hibernation, and improved myocardial wall motion.

Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia.

BACKGROUND: Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE) release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ) rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. METHODS: Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED). Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET) expression were evaluated as correlative measurements. RESULTS: The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. CONCLUSIONS: Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system signaling in the absence of systolic impairment.

Effects of mitral valve surgery on myocardial energetics in patients with severe mitral regurgitation.

BACKGROUND: Hemodynamically significant mitral regurgitation (MR) may alter left ventricular (LV) myocardial energy requirements. The effects of MR and subsequent corrective mitral valve (MV) surgery on myocardial energetics are not well understood. A better understanding of myocardial energetics and the LV responses to changes in preload and afterload may assist with the understanding of mitral regurgitation and its effect on the LV. We sought to determine the effects of MV surgery on forward stroke work, myocardial oxidative metabolism, and myocardial efficiency. METHODS AND RESULTS: Prospectively enrolled patients with chronic, severe, nonischemic mitral regurgitation underwent echocardiography, radionuclide angiography, and C-11 acetate positron emission tomography to measure LV volumes, ejection fraction, and oxidative metabolism before and 1 year after MV surgery. Forward and total stroke work corrected for oxidative metabolism was used to estimate efficiency using the work metabolic index. Fourteen patients (age, 59+/- 8 years) with myxomatous MV were enrolled. One year after MV surgery, there was a reduction in LV end-diastolic and end-systolic volumes (231+/-86 to 131+/-21 mL; P<0.01 and 98+/-53 to 55+/-17 mL; P<0.01). Forward stroke volume increased (58.1+/-15.0 to 75.5+/-23 mL; P<0.01), LV ejection fraction was preserved without a significant change in oxidative metabolism. Forward work metabolic index improved (4.99+/-1.32 x 10(6) to 6.59+/-2.45 x 10(6) mm Hg x mL/m(2); P=0.02). This was not at the expense of total work metabolic index, which was preserved. CONCLUSIONS: MV surgery has a beneficial effect on forward stroke volume and forward work metabolic index without adverse effects on oxidative metabolism or total work metabolic index.

Mobile ventricular thrombus arising from the mitral annulus in patients with dense mitral annular calcification.

Mitral annular calcification (MAC) has been considered a risk factor for thrombo-embolic disease. Superimposed thrombus formation on MAC has not been well described as a possible underlying mechanism for this association. We report three patients with mobile left ventricular (LV) thrombus arising from the LV aspect of severe calcified mitral annulus in the setting of normal LV function, mitral valve function, and sinus rhythm.

Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function.

OBJECTIVE: Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction. METHODS: Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 x 10(6) mesenchymal progenitor cells, 1 x 10(6) endothelial progenitor cells, 5 x 10(5) mesenchymal progenitor cells plus 5 x 10(5) endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed. RESULTS: Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% +/- 15.2%, P < .001), with no observed difference between cell-treated groups (P > or = .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% +/- 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% +/- 11.1%, mesenchymal progenitor cell: 53.0% +/- 6.0%, and phosphate-buffered saline: 49.6% +/- 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% +/- 5.1% vs mesenchymal progenitor cell: 22.5% +/- 5.4% and phosphate-buffered saline: 21.3% +/- 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment. CONCLUSION: Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.

Guidelines for the provision of echocardiography in Canada: recommendations of a joint Canadian Cardiovascular Society/Canadian Society of Echocardiography Consensus Panel.

Recognizing the central role of echocardiographic examinations in the assessment of most cardiac disorders and the need to ensure the provision of these services in a highly reliable, timely, economical and safe manner, the Canadian Cardiovascular Society and Canadian Society of Echocardiography undertook a comprehensive review of all aspects influencing the provision of echocardiographic services in Canada. Five regional panels were established to develop preliminary recommendations in the five component areas, which included the echocardiographic examination, the echocardiographic laboratory and report, the physician, the sonographer and indications for examinations. Membership in the panels was structured to recognize the regional professional diversity of individuals involved in the provision of echocardiography. In addition, a focus group of cardiac sonograhers was recruited to review aspects of the document impacting on sonographer responsibilities and qualification. The document is intended to be used as a comprehensive and practical reference for all of those involved in the provision of echocardiography in Canada.

Comparison of real-time 3-dimensional echocardiography with conventional 2-dimensional echocardiography in the assessment of structural heart disease.

We evaluated the diagnostic use of a real-time 3-dimensional (3D) echocardiographic system in 106 patients referred for echocardiography during a 4-month period. Real-time 3D echocardiography was performed and recorded in parallel with a routine, comprehensive 2-dimensional (2D) study. The diagnoses were exclusively on the basis of 2D findings. The 3D volumes were sliced offline in the 3 dimensions to selectively display specific cardiac structures and reviewed independent of the 2D findings. The 3D studies were graded as: A, new finding not on 2D studies; B, useful anatomic perspective; C, equivalent to 2D studies; or D, missed 2D findings. Compared with 2D echocardiography, 3D echocardiography was graded A in 7 (7%), B in 19 (18%), C in 65 (61%), and D in 15 (14%) cases. In the 26 grade-A and grade-B studies, mitral valve disease and congenital heart disease accounted for 16 (61%) cases. Suboptimal image quality was present in 7 (47%) of the 15 grade-D studies. Thus, real-time 3D echocardiography yields anatomic information comparable with conventional 2D echocardiography in the majority of patients. It can provide new and useful anatomic insight, particularly in patients with mitral valve disease and congenital heart disease. Suboptimal image quality remains a problem for real-time 3D echocardiography in some patients.