[TRANSCATHETER AORTIC VALVE REPLACEMENT - CURRENT STATE].

INTRODUCTION: Trans-catheter aortic valve implantation is a relatively novel procedure first performed in 2002, which has undergone rapid development since then. Nowadays, it is performed in many medical centers throughout the world. The main indication for the procedure is treatment of severe symptomatic aortic valve stenosis. At the outset, the procedure was indicated for very sick patients with prohibitive surgical risk. Nevertheless, broad employment of this procedure, rapid development of the medical equipment required for it, and improvement in the skill of the medical personnel involved in it, eventually led to its elevation to a different grade. Currently, there is evidence that this procedure could be better than the surgical intervention in a broad patient population, by no means the sickest of them. This paper reviews the medical literature on the procedure including the relevant medical equipment, different modes of its deployment, the main complications of the procedure, its main indications and contraindications, and the outcome of the patients undergoing it, as based on the studies performed to this end.

Identification of hibernating myocardium with quantitative intravenous myocardial contrast echocardiography: comparison with dobutamine echocardiography and thallium-201 scintigraphy.

BACKGROUND: There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl(201)) scintigraphy. METHODS AND RESULTS: Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl(201) tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function (P<0.001). The best MCE parameter for predicting functional recovery was Peak MCIxbeta, an index of myocardial blood flow (area under the curve, 0.83). MCE parameters were higher in segments with contractile reserve and Tl(201) uptake > or =60% (P<0.05) and identified viable segments without contractile reserve by DE. The sensitivity of Peak MCIxbeta >1.5 dB/s for recovery of function was 90% and was similar to Tl(201) scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl(201) and DE (63%, 45%, and 54%, respectively; P<0.05). CONCLUSIONS: MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl(201) scintigraphy.

Microvascular structural correlates of myocardial contrast echocardiography in patients with coronary artery disease and left ventricular dysfunction: implications for the assessment of myocardial hibernation.

BACKGROUND: Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. METHODS AND RESULTS: MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (beta) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (<100 microm) density, capillary density and area, arteriolar and venular density, and percent collagen content were quantitated with immunohistochemistry. Peak MCI correlated with microvascular density (r=0.59, P<0.001) and capillary area (r=0.64, P<0.001) and inversely correlated with percent collagen content (r=-0.45, P=<0.01). The best relation was observed when the ratio of peak MCI in the 2 biopsied segments in each patient was compared with the ratio of microvascular density and capillary area (r=0.84 and 0.87, respectively; P<0.001). A significant overlap in microvascular density was seen between segments with and without recovery of function. The new MCE indices of blood velocity (beta) and flow (peak MCIxbeta) better identified recovery of function compared with microvascular density and the sole use of peak MCI. CONCLUSIONS: Microvascular integrity is a significant determinant of maximal MCI in humans. MCE indices of blood velocity and flow are important parameters that predict recovery of function after revascularization.

Active interstitial remodeling: an important process in the hibernating human myocardium.

OBJECTIVES: The purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery. BACKGROUND: Myocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium. METHODS: We evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 ((201)Tl) tomography before coronary bypass surgery. During surgery, transmural myocardial biopsies were performed guided by transesophageal echocardiography. Myocardial biopsies were stained immunohistochemically to investigate fibroblast phenotype and examine evidence of active remodeling in the heart. RESULTS: Among the 29 biopsied segments included in the study, 24 showed evidence of systolic dysfunction. The majority of dysfunctional segments (86.4%) were viable ((201)Tl uptake > or = 60%). After revascularization, 12 dysfunctional segments recovered function as assessed with an echocardiogram three months after bypass surgery. Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin heavy chain (SMemb) were noted in dysfunctional segments, predominantly located in border areas adjacent to viable myocardial tissue. Segments with recovery had higher SMemb expression (0.46 +/- 0.16% [n = 12] vs. 0.10 +/- 0.02% [n = 12]; p < 0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 +/- 0.026 [n = 12] vs. 0.07 +/- 0.01 [n = 12]; p < 0.05) compared with segments without recovery, indicating fibroblast activation and higher cellularity of the fibrotic areas. In addition, interstitial deposition of the matricellular protein tenascin, a marker of active remodeling, was higher in hibernating segments than in segments with persistent dysfunction (p < 0.05), suggesting an active continuous fibrotic process. Multiple logistic regression demonstrated a significant independent association between SMemb expression and functional recovery (p < 0.01). CONCLUSIONS: Fibroblast activation and expression of SMemb and tenascin provide evidence of continuous remodeling in the cardiac interstitium of the hibernating myocardium, an important predictor of recovery of function after revascularization.

Diagnostic accuracy and cost-effectiveness of contrast echocardiography on evaluation of cardiac function in technically very difficult patients in the intensive care unit.

Echocardiographic assessment of cardiac function can be quite difficult in the intensive care unit and may require transesophageal echocardiography (TEE). We therefore compared harmonic imaging alone or in combination with contrast to TEE in 32 consecutive patients in the intensive care units who were considered technically very difficult (> or =50% of the 16 segments not visualized from any view). Excellent or adequate endocardial visualization was achieved in 13% of segments with fundamental imaging, 34% with harmonic imaging, and 87% with contrast (p < 0.0001); the latter success rate was similar to TEE (87% vs 90%; p = NS). When TEE was used as the standard, agreement in exact interpretation of wall motion increased from 48% for fundamental imaging to 58% with harmonic imaging, and reached 70% with contrast (p <0.0001). Contrast had the best sensitivity (89%) for detecting wall motion abnormalities. Estimation of ejection fraction was possible in 31% with fundamental imaging, 50% with harmonic imaging, and in 97% with contrast. Ejection fraction quantitated by contrast enhancement correlated best with TEE (r = 0.91). Cost-effectiveness analysis revealed that contrast echo was cost-effective compared with TEE in determining regional and global ventricular function, with a cost saving of 3% and 17%, respectively. Thus, contrast echocardiography provides an accurate, safe, and cost-effective alternative to TEE for evaluating ventricular function in technically very difficult studies.

Quantitative parameters of myocardial perfusion with contrast echocardiography in human beings: Influence of triggering mode.

To facilitate quantitation of myocardial contrast echocardiography (MCE) in human beings, dual- or triple-triggered flash imaging has been advocated. However, the effect of this modality on quantitative blood-flow parameters of MCE is not known. Accordingly, MCE was quantitated in 71 myocardial regions of 22 patients (age: 57 +/- 16 years) during continuous infusion of Optison (12-18 mL/h). Two sets of images with end-systolic gating (1:1, 1:2, 1:3, 1:4, 1:6, and 1:8) from the apical 4-chamber view were acquired: single and dual triggering for the first 15 patients; and single and triple triggering for the other 7 patients. During gated imaging, MCE of the first, second, and third frame were quantitated. Curves of intensity versus pulsing intervals were fitted to an exponential function: y = A (1-e(-betat)). Where beta is myocardial blood velocity or the rate of rise of myocardial contrast intensity (MCI), and A is myocardial blood volume or the plateau of MCI reached. Continuous imaging, and the second and third frame in 1:1 gating only, provided similar intensity to precontrast imaging. Beyond 1:1 gating, MCI of the second frame in dual triggering mode gradually increased with incremental pulsing interval. This was still present but less pronounced in triple triggering. During dual and triple triggering, a lower beta was observed compared with single triggering. Application of image subtraction with the flash procedure further decreased beta, A, and the A(*)beta product, a quantitative parameter of blood flow by MCE. Thus, flash subtraction imaging alters the quantitative parameters of myocardial blood velocity and flow derived from MCE. Continuous imaging, and the second or third frame in flash imaging at 1:1 gating only, result in MCI similar to precontrast imaging and can be used for background subtraction to quantitate MCE parameters.

Use of an automatic application for wall motion classification based on longitudinal strain: is it affected by operator expertise in echocardiography? A multicentre study by the Israeli Echocardiography Research Group.

AIMS: Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. METHODS AND RESULTS: We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). CONCLUSION: Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated 'second opinion' for experienced echocardiographers.

A new tool for automatic assessment of segmental wall motion based on longitudinal 2D strain: a multicenter study by the Israeli Echocardiography Research Group.

BACKGROUND: Identification and quantification of segmental left ventricular wall motion abnormalities on echocardiograms is of paramount clinical importance but is still performed by a subjective visual method. We constructed an automatic tool for assessment of wall motion based on longitudinal strain. METHODS AND RESULTS: Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per patient. Ranges of peak systolic longitudinal strain that best fit VSS (by receiver operating characteristic analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of wall motion scores between both methods in 89.6% of normal, 39.5% of hypokinetic, and 69.4% of akinetic segments. Correlation between methods was r=0.63 (P<0.0001). Interobserver and intraobserver reliability using interclass correlation for scoring segmental wall motion into 3 scores by ASS was 0.82 and 0.83 and by VSS 0.70 and 0.69, respectively. Compared with VSS (majority rule), ASS had a sensitivity, specificity, and accuracy of 87%, 85%, and 86%, respectively. ASS and VSS had similar success rates for correct identification of wall motion abnormalities in territories supplied by culprit arteries. VSS had greater specificity and positive predictive values, whereas ASS had higher sensitivity and negative predictive values for identifying the culprit artery. CONCLUSIONS: Automatic quantification of wall motion on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings.

Reliability of visual assessment of global and segmental left ventricular function: a multicenter study by the Israeli Echocardiography Research Group.

BACKGROUND: The purpose of this multicenter study was to determine the reliability of visual assessments of segmental wall motion (WM) abnormalities and global left ventricular function among highly experienced echocardiographers using contemporary echocardiographic technology in patients with a variety of cardiac conditions. METHODS: The reliability of visual determinations of left ventricular WM and global function was calculated from assessments made by 12 experienced echocardiographers on 105 echocardiograms recorded using contemporary echocardiographic equipment. Ten studies were reread independently to determine intraobserver reliability. RESULTS: Interobserver reliability for visual differentiation between normal, hypokinetic, and akinetic segments had an intraclass correlation coefficient of 0.70. The intraclass correlation coefficient for dichotomizing segments into normal versus other abnormal was 0.63, for hypokinetic versus other scores was 0.26, and for akinetic versus other scores was 0.58. Similar results were found for intraobserver reliability. Interobserver reliability for WM score index was 0.84 and for left ventricular ejection fraction was 0.78. Similar values were obtained for the intraobserver reliability of WM score index and ejection fraction. Compared to angiographic data, the accuracy of segmental WM assessments was 85%, and correct determination of the culprit artery was achieved in 59% of patients with myocardial infarctions. CONCLUSION: Among experienced readers using contemporary echocardiographic equipment, interobserver and intraobserver reliability was reasonable for the visual quantification of normal and akinetic segments but poor for hypokinetic segments. Reliability was good for the visual assessment of global left ventricular function by WM score index and ejection fraction.

Dipyridamole-induced abnormal Tl-201 lung uptake in patients with normal myocardial perfusion: a marker of increased left ventricular filling pressures.

BACKGROUND: The mechanism of dipyridamole-induced abnormal increased T1-201 lung uptake in patients without coronary artery disease is poorly understood. The purpose of this study was to evaluate the relation between dipyridamole-induced abnormal T1-201 lung uptake and left ventricular (LV) diastolic indexes using Doppler, color M-mode and Tissue Doppler modalities at rest, and at dipyridamole stress echocardiograpy (DSE) in patients with normal myocardial perfusion and LV function. METHODS AND RESULTS: 18 consecutive patients (mean age 64 +/- 7 years) with normal myocardial perfusion and increased lung T1-201 uptake on dipyridamole stress-redistribution single photon emission computed tomography (SPECT) were included in our study. These patients were compared with 18 age-matched control patients with normal perfusion and normal T1-201 lung uptake. All patients underwent DSE. A good correlation was found between the T-201 lung uptake, the peak early velocity of mitral inflow (E, r = 0.57) and estimated pulmonary capillary wedge pressure (PCWP = 1.24[E/Ea] + 1.9, r = 0.68). In patients with increased L/H ratio compared to control group, the E and the PCWP were significantly higher at baseline 81 +/- 18 vs 68 +/- 11 (cm/s) and 13 +/- 3 vs 10.2 +/- 2 (mmHg). An additional significant increase of E to 91 +/- 23 (cm/s (P = 0.001)) and PCWP to 14.8 +/- 3 (P = 0.005) after dipyridamole administration was seen; in contrast to a nonsignificant change observed in control group. For the detection of a dipyridamole induced PCWP >12 mmHg, a L/H ratio of >/=50% had a sensitivity of 72% and a specificity of 83%, resulting in a positive and a negative predictive value of 81% and 75%, respectively. CONCLUSIONS: A dipyridamole-induced abnormal T1-201 lung uptake in patients with normal myocardial perfusion and systolic function is predictive of elevated filling pressures at rest and in response to dipyridamole administration, probably reflecting an intrinsic resting diastolic dysfunction and a further abnormal response to vasodilatation.

Evidence for an active inflammatory process in the hibernating human myocardium.

Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable ((201)Tl uptake >/= 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 +/- 3.1 cells/mm(2), n = 12 versus 8.6 +/- 0.9 cells/mm(2), n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.