Symptomatic mechanical heart valve thrombosis: high morbidity and mortality despite successful treatment options.

BACKGROUND: Recommendations for treatment of mechanical prosthetic heart valve thrombosis (PVT) include systemic thrombolysis and/or reoperation. Data on complications and outcome are limited. METHODS: Clinical and echocardiographic findings of 17 patients with mechanical PVT were reviewed. Complications and outcome of surgery and/or thrombolysis were analysed. Prospective follow-up was obtained. RESULTS: Symptomatic PVT occurred 8.4 +/- 7.2 years after mechanical valve replacement at mean age 55 +/- 15 years. Thrombosis involved the mitral valve in 12 patients (71%), the aortic valve in 4 (24%) and the tricuspid valve in one (6%). The reason for PVT was inadequate anticoagulation in 11 patients (65%), endomyocardial fibrosis in 2 (12%) and unknown in 4 (24%). Prior to diagnosis, systemic emboli occurred in 6 patients (35%). Thirteen patients (76%) presented in functional class NYHA IV. Haemodynamic valve obstruction was documented by echocardiography in 15 patients (88%). Treatment included primary reoperation in 12 patients (71%), thrombolysis with urokinase in 3 (18%) (with reoperation in 1), reinstitution of adequate anticoagulation in one (6%); death occurred before treatment in one (6%). Intraoperatively, both pannus and thrombus were found in 5 of 13 patients (38%). Treatment-related emboli occurred in 5 patients (29%), to the brain in 3, to the legs in one and to a coronary artery in one. Five patients died (mortality 29%) within 30 days due to multiorgan failure/septicaemia (3 patients), congestive heart failure (1), or cerebral emboli (1). Follow-up after 28 +/- 28 months in the 12 surviving patients was unremarkable. CONCLUSIONS: The most common aetiology for obstructive PVT is thrombus formation due to inadequate anticoagulation. PVT remains a serious complication with high morbidity and mortality despite aggressive treatment by thrombolysis and/or surgery. Surgery is often needed due to the frequent presence of pannus and/or large thrombi. However, long-term prognosis after successful treatment of PVT is excellent.

Doppler mirror image artifacts mimicking mitral regurgitation in patients with mechanical bileaflet mitral valve prostheses.

AIMS: To characterize the origin and mechanisms of generation of Doppler mirror images in the left atrium observed in patients with mechanical bileaflet mitral valve prosthesis. We hypothesized that these systolic colour Doppler images are artifactual and generated by reflection of the left ventricular outflow tract flow at the leaflet of the mitral valve prosthesis. METHODS AND RESULTS: Fifty patients with mechanical bileaflet mitral valves were prospectively examined by means of transthoracic Doppler-echocardiography. From different apical views, the left atrium was carefully interrogated for systolic colour flow signals, which were further analysed by pulsed wave Doppler. In all patients, a systolic colour Doppler signal was detected in the left atrium. Pulsed wave Doppler analysis revealed a low velocity signal (= mirror image) corresponding to the shape and duration of the left ventricular outflow tract signal. The peak velocities of these mirror images, however, were consistently lower than the velocities obtained from the left ventricular outflow tract. In addition, if paravalvular mitral valve leakage was present, a high velocity signal identical to the duration of mitral regurgitation time was detected outside the ring of the prosthesis. CONCLUSIONS: Mirror image artifacts mimicking mitral regurgitation occur in patients with mechanical mitral valves prosthesis. As mirror image artifacts can be specifically identified by analysis of shape. velocity, and duration of pulsed wave Doppler spectra, their identification will help to avoid misinterpretation of both spectral and colour Doppler signals in patients with prosthetic mitral valves.

Effect of repetitive episodes of exercise induced myocardial ischaemia on left ventricular function in patients with chronic stable angina: evidence for cumulative stunning or ischaemic preconditioning?

BACKGROUND: Myocardial stunning is known to occur following a single episode of effort angina in patients with coronary artery disease. The effect on left ventricular (LV) function of repeated episodes of ischaemia is unknown. OBJECTIVES: To investigate the effects of repeated episodes of exercise induced ischaemia on LV function in patients with chronic stable angina. METHODS: Patients with significant coronary artery disease and normal LV function underwent two episodes of symptom limited treadmill exercise separated by three different time intervals: either 30 minutes (group A, n = 14); 60 minutes (group B, n = 14); or 240 minutes (group C, n = 14). Quantitative stress echocardiography was performed at repeated intervals between the two exercises and for 240 minutes following the second test. RESULTS: For all groups there was no difference between the degree of ischaemia judged by maximal ST depression during the two tests. All episodes of exercise induced ischaemia produced prolonged abnormalities of LV systolic and diastolic function despite rapid normalisation of haemodynamic and ECG changes. In group A (30 minutes) these abnormalities were less pronounced after the second test than after the first, while in group B (60 minutes) they were more severe and long lasting. In group C (240 minutes) the two tests produced similar abnormalities of LV function. CONCLUSIONS: Prolonged abnormalities of LV function occurred following exercise induced ischaemia with a time course consistent with myocardial stunning. The severity and degree of LV dysfunction caused by a further episode of ischaemia appear to be dependent on the time interval between ischaemic episodes.

Assessment of transmural distribution of myocardial perfusion with contrast echocardiography.

BACKGROUND: We hypothesized that by using our newly defined method of destroying microbubbles and measuring their rate of tissue replenishment, we could assess the transmural distribution of myocardial perfusion. METHODS AND RESULTS: We studied 12 dogs before and after creation of left anterior descending coronary artery stenoses both at rest and during hyperemia (n=62 stages). Microbubbles were administered as a constant infusion, and myocardial contrast echocardiography (MCE) was performed with the use of different pulsing intervals. The video intensity versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y=A(1-ebetat), where A reflects microvascular cross-sectional area (or myocardial blood volume), and beta reflects mean myocardial microbubble velocity. The product A . beta represents myocardial blood flow (MBF). Average values for these parameters were derived from the endocardial and epicardial regions of interest placed over the left anterior descending coronary artery bed. Radiolabeled microsphere-derived MBF was also measured from the same regions. There was poor correlation between radiolabeled microsphere-derived MBF and A-endocardial/epicardial ratios (EER) (r=0.46). The correlation with beta-EER was better (r=0. 69, P<0.01). The best correlation with radiolabeled microsphere-derived MBF-EER was noted with A . beta-EER (r=0.88, P<0. 01). CONCLUSIONS: The transmural distribution of myocardial perfusion can be accurately assessed with MCE with the use of our newly described method of tissue replenishment of microbubbles after their ultrasound-induced destruction. In the model studied, an uncoupling of the transmural distribution of MBF and myocardial blood volume was observed during reversal of the MBF-EER.

Spontaneous redistribution after reperfusion: a unique property of AIP 201, an ultrasound contrast agent.

OBJECTIVES: We sought to determine the mechanism of spontaneous redistribution of AIP 201 microbubbles after reperfusion from a single left heart injection performed during coronary occlusion. BACKGROUND: AIP 201, an ultrasound contrast agent consisting of 10-microm sized microbubbles, has demonstrated spontaneous myocardial redistribution in preliminary studies. METHODS: Myocardial video intensity (VI) and radiolabeled microsphere-derived myocardial blood flow (MBF) were measured serially after reperfusion in seven dogs undergoing an AIP 201 injection during coronary occlusion. The behavior of these bubbles was also assessed in the rat spinotrapezius muscle using intravital microscopy (IM), both with and without ultrasound. The effect of ultrasound on these bubbles was also determined in vitro. RESULTS: A spontaneous and gradual increase in myocardial VI was noted after reperfusion, which was related to the magnitude of increase in MBF to that region (r=0.82, p < 0.001). On IM, most of the microbubbles were seen entrapped in small arterioles. Some larger arterioles had aggregates of microbubbles that periodically became dislodged and moved downstream. This behavior was not affected in vivo by ultrasound. In vitro, however, microbubble aggregation was noted only during ultrasound exposure. CONCLUSIONS: The magnitude of redistribution of AIP 201 microbubbles to the reperfused myocardium is related to changes in MBF and occurs from their dislodgement from microbubble aggregates entrapped in large arterioles. In vitro microbubble aggregation seen during ultrasound exposure was not reproduced in vivo. These results may have important implications for studying the effects of interventions in acute coronary syndromes and after coronary artery bypass graft surgery.

Randomized, double-blind crossover study to investigate the effects of amlodipine and isosorbide mononitrate on the time course and severity of exercise-induced myocardial stunning.

BACKGROUND: Myocardial stunning may cause prolonged left ventricular dysfunction after exercise-induced ischemia that can be attenuated by calcium antagonists in animal models. To assess their effects in humans, we performed a randomized, double-blind crossover study comparing the calcium antagonist amlodipine (10 mg once daily) versus isosorbide mononitrate (ISMN, 50 mg once daily) on postexercise stunning. METHODS AND RESULTS: Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress echocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emission computed tomography perfusion scans at peak stress to quantify the ischemic burden. Exercise time (P=1), maximum ST depression (P=0.48), and sestamibi single-photon emission computed tomography scores (P=0.17) were unchanged between treatments. Stunning occurred more often with ISMN than amlodipine (82% versus 48%). The global and segmental stress echocardiography parameters of stunning were attenuated in patients while taking amlodipine compared with ISMN. Shortening fractions and ejection fractions were less impaired 30 minutes after exercise in patients receiving amlodipine (3.5+/-1.4% versus 2.5+/-1.4%, P=0.014, and 59.7+/-5.4% versus 54.5+/-8%, P<0.001); similarly, the isovolumic relaxation period was less prolonged with amlodipine (93+/-15.5 versus 106.3+/-14.9 ms, P=0.018). CONCLUSIONS: Despite comparable levels of ischemia, amlodipine attenuated stunning when compared with ISMN. This beneficial effect may relate to a prevention of the calcium overload implicated in the pathogenesis of stunning.

Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue.

BACKGROUND: Our aim was to observe ultrasound-induced intravascular microbubble destruction in vivo and to characterize any resultant bioeffects. METHODS AND RESULTS: Intravital microscopy was used to visualize the spinotrapezius muscle in 15 rats during ultrasound delivery. Microbubble destruction during ultrasound exposure caused rupture of < or = 7-microm microvessels (mostly capillaries) and the production of nonviable cells in adjacent tissue. The number of microvessels ruptured and cells damaged correlated linearly (P<0.001) with the amount of ultrasound energy delivered. CONCLUSIONS: Microbubbles can be destroyed by ultrasound, resulting in a bioeffect that could be used for local drug delivery, angiogenesis, and vascular remodeling, or for tumor destruction.

Three-dimensional myocardial contrast echocardiography: validation of in vivo risk and infarct volumes.

OBJECTIVES: The aim of this study was to determine whether three-dimensional (3D) myocardial contrast echocardiography (MCE) could provide an accurate in vivo assessment of risk and infarct volumes. BACKGROUND: MCE has been shown to accurately define risk area and infarct size in single tomographic slices. The ability of this technique to measure risk and infarct volumes by using three-dimensional echocardiography (3DE) has not been determined. METHODS: Fifteen open chest dogs underwent variable durations of coronary artery occlusion followed by reperfusion. At each stage, MCE was performed by using left atrial injection of AIP201, a deposit microbubble with a mean diameter of 10 +/- 4 microm and a mean concentration of 1.5 x 10(7) x ml(-1). Images were obtained over a 180 degree arc with use of an automated rotational device and were stored in computer as a 3D data set. Postmortem risk area and infarct size were measured in six to eight left ventricular short-axis slices of equal thickness using technetium-99m autoradiography and tissue staining, respectively. MCE images corresponding to these planes were reconstructed off-line. RESULTS: A close linear relation was noted between the volume of myocardium not showing contrast enhancement on 3D MCE during coronary occlusion and postmortem risk volume (y = 1.2x - 3.0, r = 0.83, SEE = 5.1, n = 15). The volume of myocardium not showing contrast enhancement on 3D MCE after reperfusion also closely correlated with postmortem infarct volume (y = 1.1x - 3.9, r = 0.88, SEE = 4.8, n = 11). No changes in systemic hemodynamic variables were noted with injections of AIP201. CONCLUSIONS: When combined with AIP201, a deposit microbubble, 3D MCE can be used to accurately determine both risk and infarct volumes in vivo. This method could be used to assess the effects of interventions that attempt to alter the infarct/risk volume ratio.