Clozapine-induced effuso-constrictive pericarditis. Case report and review of the literature.

Clozapine is a widely used antipsychotic medication and is effective against both positive and negative symptoms of schizophrenia. However, clozapine use should be monitored closely due to its side effects profile. The main side effects include cardiorespiratory symptoms, seizures and agranulocytosis. We report a case of effuso-constrictive pericarditis soon after being started on clozapine therapy, whose symptoms improved after discontinuation of clozapine. The literature is reviewed and importance of monitoring is discussed.

Variation of anatomic valve area during ejection in patients with valvular aortic stenosis evaluated by two-dimensional echocardiographic planimetry: comparison with traditional Doppler data.

OBJECTIVES: Flow variations can affect valve-area calculation in aortic stenosis and lead to inaccuracies in the evaluation of the stenosis. Knowing that transvalvular flow varies normally within one beat, we designed this study to assess the response of the valve to intrabeat variation of flow during systole. Results were compared with flow-derived measurements. BACKGROUND: Technological improvements now allow us to evaluate aortic valve area directly by short axis planimetry. This offers the possibility to perform serial planimetries during one ejection phase and analyze the intrabeat dynamic behavior of the stenotic-aortic valve and compare these measurements with flow-derived measurements. METHODS: Forty echocardiograms displaying different degrees of aortic stenosis were analyzed by frame-by-frame planimetry of the valve area from onset of opening to complete closure. Maximal-mean area, opening and closing rates and ejection times were obtained and compared with Doppler-derived data. RESULTS: Valve area varied during ejection. Stenotic valves opened and closed more slowly than normals and remained maximally open for a shorter period. Mean area by Doppler data corresponded more closely to maximal than to mean-planimetered area. Duration of flow was shorter than valve opening in severely stenotic valves. Discrepancies between Doppler-derived and two-dimensional (2D) measurements decreased in less stenotic valves. CONCLUSIONS: Our observations reveal striking differences between the dynamics of normal and stenotic valves. Surprisingly, Doppler-derived mean-valve area correlated better with maximal-anatomic area than with mean-anatomic area in patients with aortic stenosis. Discrepancies between duration of flow and valve opening could explain this phenomenon.

Clinical application of transthoracic volume-rendered three-dimensional echocardiography in the assessment of mitral regurgitation.

Two-dimensional echocardiography (2-DE) and Doppler methods are generally used for assessing mechanisms and severity of mitral regurgitation (MR). Recently, 3-dimensional echocardiography (3-DE) has been applied successfully in various cardiac disorders, but its value in evaluating the mechanism and the severity of MR are not known. We studied 30 patients with MR using 2-DE and 3-DE. Volume-rendered gray-scale 3-DE images of the mitral valve apparatus and MR jets were reconstructed. Maximal volume of the MR jet by 3-DE was compared with mitral regurgitant volume and fraction, regurgitant jet area and the ratio of jet area to left atrial area, and semiquantitative grading derived from 2-DE methods. Our results demonstrated that 3-DE aided in a better depiction of the mitral apparatus and its abnormalities in 70% of the patients. The origin, direction, and morphology of the MR jet were better delineated in 3-DE volumetric display. Quantitative analysis, however, showed only a weak to moderate correlation between 3-DE maximal MR jet volume and 2-DE mitral regurgitant volume (y = 0.5x + 11.4, r = 0.7), regurgitant fraction (y = 0.5x + 8.2, r = 0.65), mitral regurgitant jet area (y = 0.2x + 5, r = 0.51), jet area to left atrial area ratio (y = 0.53x + 7.6, r = 0.54), and semiquantitative grading of MR (y = 9.1x - 1.8, r = 0.74). In conclusion, 3-DE aids in a better understanding of the mechanisms of MR and morphology of the regurgitant jets. Its quantitative ability, when reconstruction of the jet alone is used, may be limited.

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.

Quantitative assessment of chronic aortic regurgitation with 3-dimensional echocardiographic reconstruction: comparison with electromagnetic flowmeter measurements.

Two-dimensional echocardiography and color Doppler are useful in the qualitative assessment of aortic regurgitation. However, color Doppler planar methods are not accurate in quantifying regurgitant flow, in part because of the complex geometry of aortic regurgitant flow events. Three-dimensional echocardiographic reconstruction is a new technique that provides dynamic 3-dimensional images of intracardiac color flow jets. We sought to determine whether the measurement of aortic regurgitant jet volume by 3-dimensional echocardiography correlated with the true regurgitant volume, measured by electromagnetic flowmeter in vivo, to accurately reflect the severity of aortic regurgitation. We performed volume-rendered 3-dimensional echocardiography in 6 sheep with surgically induced chronic eccentric aortic regurgitation. We obtained a total of 22 aortic regurgitation states by altering loading conditions. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flowmeters. The maximum aortic regurgitant jet volume by 3-dimensional echocardiography and the maximum jet area by 2-dimensional echocardiography were measured and compared with electromagnetic flowmeter data. By electromagnetic flowmeter, aortic regurgitant flow rate varied from 0.14 to 3.1 L/min (mean 1. 25 +/- 0.78); aortic regurgitant stroke volume varied from 1 to 34 mL/beat (mean 12 +/- 8), and regurgitant fraction varied from 3% to 42% (mean 25% +/- 12%). The maximum jet volume by 3-dimensional echocardiography correlated very well with the aortic regurgitant stroke volume (r = 0.92; P <.0001), with the mean regurgitant flow rate (r = 0.87; P <.0001), and with the regurgitant fraction (r = 0. 87; P <.0001) derived from electromagnetic flowmeter. Both intraobserver and interobserver variability on the measurement of the jet volume by 3-dimensional echocardiography were excellent (r = 0.98; P <.0001 and r = 0.90; P <.001, respectively). The maximum jet area by 2-dimensional echocardiography did not correlate with the aortic regurgitant stroke volume (r = 0.41; P = not significant) and related poorly with the regurgitant fraction (r = 0.52; P <.05) by electromagnetic flowmeter. Dynamic 3-dimensional echocardiography can allow better determination of the geometry of the aortic regurgitant jet and may assist of quantifying the severity of aortic regurgitation.

Mitral repair best practice: proposed standards.

OBJECTIVES: To define best practice standards for mitral valve repair surgery. DESIGN: Development of standards for process and outcome by consensus. SETTING: Multidisciplinary panel of surgeons, anaesthetists, and cardiologists with interests and expertise in caring for patients with severe mitral regurgitation. MAIN OUTCOME MEASURES: Standards for best practice were defined including the full spectrum of multidisciplinary aspects of care. RESULTS: 19 criteria for best practice were defined including recommendations on surgical training, intraoperative transoesophageal echocardiography, surgery for atrial fibrillation, audit, and cardiology and imaging issues. CONCLUSIONS: Standards for best practice in mitral valve repair were defined by multidisciplinary consensus. This study gives centres undertaking mitral valve repair an opportunity to benchmark their care against agreed standards that are challenging but achievable. Working towards these standards should act as a stimulus towards improvements in care.

Severe coronary vasospasm associated with hyperthyroidism causing myocardial infarction.

A 48 year old woman presented with angina after an anterior myocardial infarction and was found to be hyperthyroid. Coronary angiography showed a stenosis of the left coronary os and a long, severe stenosis of the left anterior descending artery which was partially relieved by glyceryl trinitrate. Three months later, after radioactive iodine treatment had rendered her euthyroid, repeat coronary angiography showed entirely normal coronary arteries. This unusual case establishes an association between hyperthyroidism and coronary vasospasm resulting in myocardial infarction.

Transoesophageal echocardiography as the sole diagnostic investigation in patients with suspected thoracic aortic dissection.

OBJECTIVES: To assess the value and limitations of using transoesophageal echocardiography as the sole diagnostic test in patients with suspected thoracic aortic dissection. DESIGN: Retrospective data review over a two year period. SETTING: A regional cardiothoracic centre. PATIENTS: Data were compiled from admission records, surgical records, and lists of patients undergoing diagnostic investigations in the hospital. Patient's notes were used to identify presentation, management, and outcome. INTERVENTIONS: Patients were managed according to the policy of our unit, which is to treat patients with dissection affecting the ascending aorta by an operation. Patients with uncomplicated dissection sparing the ascending aorta are initially managed medically. MAIN OUTCOME MEASURES: In hospital and two year follow-up of patients who were investigated by transoesophageal echocardiography alone. RESULTS: Of 48 patients referred, 45 underwent transoesophageal echocardiography. Dissection was confirmed in 22 patients. Transoesophageal echocardiography showed the proximal extent of the dissection in 21/22 (96%) and only one patient required a further diagnostic investigation. Ten patients with dissection of the ascending aorta underwent graft replacement of the ascending aorta; operative mortality was 10% and their two year survival was 80%. Of the eight patients with dissection of the descending aorta, six were discharged home, and five were alive at two years. No patient without evidence of dissection on their initial transoesophageal echocardiographic examination required re-investigation into possible dissection in the two years after discharge. CONCLUSIONS: In patients with suspected thoracic dissection transoesophageal echocardiography rapidly and safely gives all the necessary diagnostic information. Further investigations, including coronary angiography, before surgery are unnecessary.

Bulls-eye display and quantitation of myocardial perfusion defects using three-dimensional contrast echocardiography.

Three-dimensional (3-D) myocardial contrast echocardiography (MCE) is able to derive parallel cutting planes of the left ventricle (LV). However, assessment of the site and extent of myocardial perfusion abnormalities has to rely on the reader's 3-D mental reconstruction from the tomograms, and a manual approach has to be employed for quantitative analysis. The objective of this study was to explore the display and quantitative capability of a bulls-eye format from contrast 3-D MCE in the assessment of perfusion abnormalities derived from a canine model of acute myocardial infarction (MI). Three-dimensional MCE data were acquired sequentially in a rotational scanning format during triggered harmonic imaging with an intravenous contrast agent. Reconstructed short-axis views of the LV were aligned in a bulls-eye format with the apex as the inner most ring. The total LV was divided into 120 sectors. The number of sectors with lack of contrast enhancement was used to derive the percent of the LV (%LV) with perfusion defect and was compared with the extent of MI calculated from postmortem triphenyl tetrazolium chloride (TTC) staining. The perfusion defect regions shown on bulls-eye images corresponded correctly with the territories of the occluded coronary arteries. Three-dimensional MCE perfusion defect mass (19.2 +/- 6.0 %LV) correlated well with anatomic MI mass (19.3 +/- 5.6 %LV; r = 0.92, SEE = 2.3%, mean differential = 0.1 +/- 2.4%). We conclude that bulls-eye display of contrast 3-D MCE demonstrates the site and extent of perfusion abnormalities in an easily appreciable manner. It also allows fast and accurate assessment of endangered myocardium.

Pacing in heart failure: improved ventricular interaction in diastole rather than systolic re-synchronization.

AIMS: To determine the mechanism by which left ventricular and biventricular pacing works. BACKGROUND: Pacing for congestive heart failure patients is employed in those with left bundle branch block on the basis that it will improve discoordinated contraction; however, the response is unpredictable. The authors propose that the mechanism of benefit is rather related to improvement of ventricular interaction in diastole (VID). VID is found in patients with a high left ventricular end-diastolic pressure (> 15 mmHg). Left ventricular pacing in these patients will delay right ventricular filling and allow greater left ventricular filling before the onset of VID. METHODS: The study group consisted of 18 congestive heart failure patients with an ejection fraction < 30% and with no more than Grade 1 mitral regurgitation. Group I comprised 10 patients with pulmonary capillary wedge pressure > 15 mmHg, four patients had a normal QRS duration and six had left bundle branch block. Group II comprised eight patients with pulmonary capillary wedge pressure < 15 mmHg, of whom five had a normal QRS duration. Haemodynamics were measured at baseline and during VDD pacing from either the left ventricle or right ventricle. RESULTS: The ratio of stroke volume/pulmonary capillary wedge pressure was calculated as an index of the relationship between left ventricular end-diastolic pressure and contractile function. This ratio was lower in group I than in group II patients (P = 0.005). In group I, haemodynamics were improved with left ventricular pacing (stroke volume/pulmonary capillary wedge pressure increased from 2.2 +/- 0.9 to 4.4 +/- 3.6, P = 0.03). In group II there was no response to either left ventricular or right ventricular pacing. The improvement with left ventricular pacing was unrelated to QRS duration (r = 0.09). CONCLUSIONS: Left ventricular pacing acutely benefits congestive heart failure patients with pulmonary capillary wedge pressure > 15 mmHg irrespective of left bundle branch block. The present data suggest that the mechanism of response may be an improvement in left ventricular filling rather than ventricular systolic re-synchronization.

Follow-up of chronic thoracic aortic dissection: comparison of transesophageal echocardiography and magnetic resonance imaging.

Because survivors of thoracic aortic dissection require follow-up to detect prognostic factors such as intimal tears, persistent flow in the false lumen, and complications associated with grafts, we compared transesophageal echocardiography (TEE) with magnetic resonance imaging (MRI) prospectively in 14 patients 1 year after their initial examination. Residual dissection was identified by both techniques in 11 patients. Flow and/or thrombus in the false lumen were detected by TEE in 10 (91 %) and 6 (55%) patients, respectively, and by MRI in 9 (82%) and 5 (45%), respectively (p = NS); more tears were detected by TEE (2.5 +/- 1.4 per patient vs 0.2 +/- 0.4; p < 0.005). Satisfactory delineation of a graft in the ascending aorta was noted in all 8 (100%) of the surgically treated patients by TEE compared with 4 (50%) by MRI (p < 0.005). The upper ascending aorta was visualized clearly in fewer patients by TEE than by MRI (7 [50%] vs 13 [93%]; p < 0.05), as were the origins of the head and neck vessels (10 [71%] vs 13 [93%], p = NS). We conclude that TEE and MRI are both suitable techniques for the follow-up of patients with aortic dissection. TEE is more sensitive in identifying prognostic factors. MRI has a complementary role, particularly in visualization of the upper ascending aorta and the head and neck vessels.

Three-dimensional echocardiographic estimation of infarct mass based on quantification of dysfunctional left ventricular mass.

BACKGROUND: Two-dimensional echocardiography is useful for estimating the extent of infarct-related wall motion abnormalities. Such estimation, however, is based on a few selected views and extrapolated for the whole left ventricle (LV). This approach does not provide us with the actual amount of dysfunctional myocardium. Volume-rendered three-dimensional echocardiography (3DE) might overcome these limitations. In this study we explored (1) how well volume-rendered 3DE delineates regional dysfunction of the infarcted LV and (2) how well dysfunctional myocardial mass quantified by 3DE reflects the actual anatomic infarct mass. METHODS AND RESULTS: 3DE was performed before and 3 hours after coronary occlusion in 16 dogs. With the LV viewed in equidistant short-axis slices, the region of dysfunction was demarcated, and the dysfunctional myocardial mass was derived from this. With triphenyltetrazolium chloride staining, anatomic infarct regions were delineated, dissected, and weighed. The anatomic infarct mass was 16.3+/-7.7 g (mean+/-SD) (range, 6.4 to 31.4 g); the dysfunctional mass estimated by 3DE was 17.4+/-9.1 g (range, 5.2 to 39.0 g). The mean difference was 1.0 g. The correlation between dysfunctional mass (y) and infarct mass (x) was y=l.lx-0.6, r=.93 (P<.0001). The percentage of LV involved in infarction was 18.2+/-5.8% (range, 9.1% to 26.1%); the percentage of LV involved in regional dysfunction was 18.3+/-6.9% (range, 7.9% to 31.2%). The mean difference was 0.1%. The correlation between percentage of LV involved in infarction (x) and percentage of LV involved in dysfunction (y) was y=1.0x-1.1, r=.92 (P<.0001). CONCLUSIONS: Volume-rendered 3DE crisply displays regional dysfunction of infarcted LV. 3DE-measured dysfunctional mass accurately reflects the anatomic infarct mass.

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.

New insights and observations in three-dimensional echocardiographic visualization of ventricular septal defects: experimental and clinical studies.

BACKGROUND: The positions, sizes, and shapes of ventricular septal defects (VSDs) can be difficult to assess by 2-dimensional echocardiography (2DE). Volume-rendered 3-dimensional echocardiography (3DE) can provide unique views of VSDs from the left ventricular (LV) side, allowing complete assessment of their circumference and spatial orientations to other anatomic structures. METHODS AND RESULTS: Seventeen experimentally created defects of various locations, sizes, and shapes were imaged and reconstructed in 9 explanted porcine hearts. From an en face projection, major and minor axis diameters of the defects were measured, and these data were compared with direct anatomic measurements. Optimal reconstructions of the VSDs were obtained in all heart specimens, accurately depicting their positions and shapes. The correlations between 3DE and anatomy for the VSD major and minor axis diameters were y=1.0x+0.3 (r=0.88, P<0.001) and y=1.0x-1.4 (r =0.89, P<0.001), respectively. Good agreement between the 2 methods was demonstrated for all measurements. Our experience from the in vitro model was then applied to patient studies. Optimal LV en face reconstructions were obtained in 45 of 51 patients, permitting detailed assessment of the positions, sizes, and shapes of the VSDs. In the 25 patients with comparative surgical measurements, the correlations between 3DE and surgery for the VSD major and minor axis diameters were y =0. 81x+2.1 (r=0.92, P<0.001) and y=0.73x+2.0 (r=0.91, P<0.001), respectively. Good agreement was demonstrated between measurements made by 3DE and those obtained at surgery. CONCLUSIONS: 3DE provides excellent visualization of various types of VSDs. From an LV en face projection, the positions, sizes, and shapes of VSDs can be accurately determined. Such precise imaging will be beneficial for surgical and catheter-based closure of difficult perimembranous and singular or multiple muscular VSDs.