Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project.

BACKGROUND: Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit. METHODS AND RESULTS: The effect of pravastatin 40 mg/d on stroke events was investigated in a prospectively defined pooled analysis of 3 large, placebo-controlled, randomized trials that included 19 768 patients with 102 559 person-years of follow-up. In all, 598 participants had a stroke during approximately 5 years of follow-up. The 2 secondary prevention trials (CARE [Cholesterol And Recurrent Events] and LIPID [Long-term Intervention with Pravastatin in Ischemic Disease]) individually demonstrated reductions in nonfatal and total stroke rates. When the 13 173 patients from CARE and LIPID were combined, there was a 22% reduction in total strokes (95% CI 7% to 35%, P:=0.01) and a 25% reduction in nonfatal stroke (95% CI 10% to 38%). The beneficial effect of pravastatin on total stroke was observed across a wide range of patient characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a primary prevention trial in hypercholesterolemic men) exhibited a similar, although smaller, trend for a reduction in total stroke. Among the CARE/LIPID participants, pravastatin was associated with a 23% reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there was no statistical treatment group difference in hemorrhagic or unknown type. CONCLUSIONS: Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes.

Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators.

BACKGROUND: The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. METHODS AND RESULTS: To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P=0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P=0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively). CONCLUSIONS: Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.

Outcome of mild periprosthetic regurgitation detected by intraoperative transesophageal echocardiography.

OBJECTIVES: The goal of this study was to determine the outcome of trivial or mild periprosthetic regurgitation (PPR) identified by intraoperative transesophageal echocardiography (TEE). BACKGROUND: The clinical significance, natural history and correlates of trivial or mild PPR detected early after surgery are unknown. METHODS: Between 1992 and 1997, 608 consecutive patients underwent isolated aortic valve replacement or mitral valve replacement at Dartmouth-Hitchcock Medical Center. Of these, 113 patients (18.3%) were found to have trivial or mild PPR at surgery by TEE. Follow-up transthoracic echocardiograms (early TTEs) were obtained within six weeks of surgery in 99.0% of patients and late TTEs (mean 2.1 years) in 54.3%. Clinical, intraoperative and outcome variables associated with PPR were identified using t test, chi-square and logistic regression analyses. RESULTS: By univariate analysis, compared with patients without PPR, patients with PPR were older, of smaller body surface area (BSA), had degenerative valve disease more often and were more likely to receive a bioprosthetic valve. By multivariate analysis, smaller BSA and the use of a bioprosthesis were the strongest predictors of PPR (p < 0.01). At early TTE, PPR was not observed (n = 56) or remained unchanged (n = 44) in all patients. At late TTE, four patients were found to have progression of their PPR. All four patients had bioprosthetic valves. Two of these patients had endocarditis, and one had primary valvular degeneration. The fourth patient had progressive PPR. CONCLUSIONS: Trivial or mild PPR is a frequent finding on intraoperative TEE. Smaller body size and the use of a bioprosthetic valve are significantly associated with PPR. The clinical significance and natural history of PPR is benign in most cases.

Systemic embolization complicating right ventricular myocardial infarction.

We describe a patient in whom multiple episodes of pulmonary and systemic embolization occurred in the setting of right ventricular infarction. The mechanism of paradoxical embolization was determined based on transesophageal echocardiographic findings that included right atrial spontaneous contrast, appendage thrombosis, patent foramen ovale with right-to-left atrial shunting, and absence of left ventricular thrombosis. Recurrent thromboembolization was prevented by percutaneous placement of a "clam-shell" occluder across the patent foramen. This clinical scenario may be more common than previously believed and is best detected with transesophageal echocardiography. Early identification of this condition can lead to prompt treatment and prevention of subsequent thromboembolic morbidity.

Transesophageal echocardiography state of the art.

Transesophageal echocardiography (TEE) is a recently popularized ultrasonic imaging technique that provides high-resolution anatomic and physiologic information due to the probe's proximity to cardiac structures. Although TEE has been available in a single-plane, two-dimensional format for many years, widespread enthusiasm for the technique has only recently developed with the addition of Doppler technology, improved image resolution, and biplanar imaging. Because of the relatively late clinical interest in TEE, literature detailing the technique's utility is at present somewhat limited. There is already good evidence documenting TEE's value in assessment of mitral valve prosthetic function, valvular regurgitation, aortic dissection, left atrial thrombus, and intraoperative monitoring of left ventricular segmental wall motion and mitral valve repair. In addition, the list of proven indications is rapidly growing. This article summarizes the present state of TEE imaging and indicates future directions of TEE clinical applicability.

Coronary hypertension and diastolic compliance in isolated rabbit hearts.

Acute pulmonary edema during hypertensive crisis has been attributed to acute left ventricular systolic failure secondary to increased afterload. We tested the hypothesis that the increase in coronary artery perfusion pressure associated with systemic hypertension could also contribute to increased left ventricular filling pressures by acutely increasing coronary intravascular volume and decreasing left ventricular diastolic compliance. Isolated isovolumic (balloon in left ventricle) normal rabbit hearts (n = 13) with pericardium removed and right ventricle vented were blood perfused at an initial coronary artery perfusion pressure of 100 mm Hg; left ventricular balloon volume was adjusted to produce an initial left ventricular end-diastolic pressure of 15 +/- 1 mm Hg; left ventricular systolic pressure was 102 +/- 3 mm Hg. When coronary perfusion pressure was increased to 130 +/- 1 mm Hg to simulate a hypertensive crisis, coronary flow increased from 2.0 +/- 0.2 to 3.0 +/- 0.2 ml/min/g left ventricle (p less than 0.001), left ventricular systolic pressure increased to 116 +/- 4 mm Hg, and isovolumic left ventricular end-diastolic pressure increased to 21 +/- 1 mm Hg (p less than 0.001), which indicated a decrease in left ventricular diastolic compliance. When coronary perfusion pressure was decreased to a physiological level of 70 mm Hg, coronary flow rate decreased to 1.4 +/- 0.1 ml/min/g left ventricle (p less than 0.001), left ventricular systolic pressure fell to 82 +/- 4 mm Hg, and left ventricular end-diastolic pressure fell to 14 +/- 1 mm Hg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of adenosine 5'-diphosphate receptor blockade in patients with cardiovascular disease.

Aspirin, which has been the mainstay of antiplatelet agent for many decades, affects a single pathway in the platelet activation process and provides incomplete protection against cardiovascular events. Aspirin also may blunt the hemodynamic effect of angiotensin-converting enzyme inhibitors. Dipyridamole may provide some additional benefit, but there is little evidence to suggest its superiority alone or in combination with aspirin compared to standard doses of aspirin. Oral platelet glycoprotein IIb/IIIa inhibitors, although initially promising, have had disappointing results in recent clinical studies. A new class of medications, the thienopyridines, blocks the activity of platelet adenosine 5'-diphosphate (ADP) receptors, thereby reducing platelet activation. This review discusses the pharmacology, clinical studies, and potential uses of these agents, which include ticlopidine and clopidogrel. ADP inhibitors, by blocking an alternate pathway of platelet activation, are slightly more effective than aspirin in reducing cardiovascular events.

Sensitivity and specificity of the echocardiographic features of cardiac amyloidosis.

Thirty-one patients with documented cardiac amyloidosis were compared to 39 control subjects with left ventricular hypertrophy to determine specific 2-dimensional echocardiographic features of amyloid. In 16 patients, increased myocardial echogenicity was present when a single short-axis view was examined, and had a sensitivity of 63% and a specificity of 74% for the diagnosis of amyloidosis. When complete echocardiograms were reviewed (15 patients), an improved sensitivity of 87% and specificity of 81% based on increased echogenicity was seen. Increased atrial septal thickness was present in 60% of amyloid patients and no controls. The combination of increased myocardial echogenicity and increased atrial thickness was 60% sensitive and 100% specific for the diagnosis of amyloidosis. The ratio of electrocardiographic voltage (S in V1 + R in V5 or V6) to left ventricular cross-sectional area also was examined. A ratio of less than 1.5 was 82% sensitive and 83% specific for amyloid (excluding the 2 patients with left bundle branch block), but added little to the diagnosis as determined from the 2-dimensional echocardiogram.

Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham Heart Study).

Normative Doppler values and determinants of left ventricular (LV) diastolic function in healthy subjects have not been fully elucidated. Subjects from the Framingham Heart Study were examined to describe reference values and determinants of echocardiographic Doppler indexes of diastolic function. One hundred twenty-seven randomly selected, rigorously defined, normal subjects, approximately evenly distributed by sex and age from the third through the eighth decades were studied by Doppler echocardiography. Normative values for 7 frequently used Doppler indexes of LV diastolic function are presented. Doppler indexes of LV diastolic function change dramatically with age; the peak velocity of early filling divided by late filling (peak velocity E/A) ranges from a mean of 2.08 +/- 0.55 for subjects in their third decade to 0.84 +/- 0.29 for those in their eighth decade. A peak velocity E/A ratio less than 1 is abnormal in subjects aged less than 40 years, but occurs in most subjects aged greater than or equal to 70 years. The high correlations between age and Doppler indexes of LV diastolic function are not greatly attenuated after adjustment for other clinical parameters associated with diastolic function; the multivariate partial correlation coefficient between age and peak velocity E/A is -0.80 (p less than 0.0001). Heart rate, PR interval, LV systolic function, sex and systolic blood pressure are minor determinants of Doppler indexes of diastolic function. Body mass index, left atrial diameter, and LV wall thickness, internal dimension and mass have little or no association with Doppler indexes in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement in mitral regurgitation after aortic valve replacement.

This study sought to determine whether there is a quantitative improvement in mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis (AS) and, if so, the mechanisms for this change. MR frequently accompanies AS. The addition of mitral valve replacement to AVR significantly increases the risk of surgery. Although previous studies have suggested a qualitative improvement in MR severity after AVR, semiquantitative analysis of this improvement has not been documented nor have the underlying mechanisms been examined. We evaluated 28 patients who had undergone 2-dimensional echo and color flow Doppler imaging an average of 1.5 +/- 2.5 months before and 2.5 +/- 4.2 months after AVR. Maximum MR area, MR percentage (MR area/left atrial area), mitral annular area, left atrial area, aortic gradient, and parameters of left ventricular geometry were measured to evaluate MR severity and to assess functional mechanisms for improvement in MR. There was a significant decrease in MR area (5.5 +/- 2.8 cm2 vs 2.5 +/- 1.9 cm2, p < or =0.0001) and MR percentage (25 +/- 11% vs 12 +/- 10% after operation, p < or =0.0001) between preoperative and postoperative studies. There was a significant reduction in aortic gradient, mitral annular area, left atrial area, and left ventricular length postoperatively. In univariate analysis, MR improvement was related to the lower preoperative left ventricular fractional area change (p = 0.027) and to the changes in fractional area change (p = 0.001) and left ventricular systolic area (p = 0.001). Thus, improvement in MR after AVR is related to changes in left ventricular function postoperatively. These data suggest that reduction in MR is due not only to decreased intraventricular pressure, but also to changes in ventricular morphology.

Transesophageal echocardiographic assessment of aortic coarctation using color, flow-directed Doppler sampling.

We report the use of color, flow-directed transesophageal Doppler in the evaluation of aortic coarctation. Transesophageal echocardiography (TEE) was used to define the aortic shelf in two adults with mild and moderate postductal coarctation, respectively. The color mosaic pattern aided in identification of the coarctation location and orifice diameter. Continuous wave and pulsed cursors were steered to provide sampling parallel to the color jet direction and gradients calculated by the modified Bernoulli formula, excluding prestenotic velocities. Measured pressure gradients were equivalent to those determined at catheterization. We conclude that color, flow-directed TEE Doppler sampling can aid in the identification and characterization of adult patients with aortic coarctation.

Effects of coronary revascularization on regional wall motion. An intraoperative two-dimensional echocardiographic study.

Although coronary artery bypass grafting effectively reduces the symptoms of myocardial ischemia, its immediate effect on regional wall motion dysfunction is not well defined. This intraoperative study was undertaken to determine whether bypass grafting improves regional wall motion in areas of preoperative ischemic dysfunction. In 17 patients undergoing coronary bypass, short-axis echocardiograms were obtained with the chest open 30 minutes before and after cardiopulmonary bypass. Regional wall motion was calculated quantitatively as the percent increase in segmental wall thickness during systole, with 40% thickening or less defined as indicating ischemic dysfunction. Qualitatively, it was evaluated by visual changes in endocardial wall motion according to a graded score (0 = normal to 4 = dyskinesia). Of the 136 segments studied, 44 (32%) had evidence of ischemic dysfunction before coronary bypass. When regional wall motion was analyzed in all 136 segments after coronary bypass, there was no significant change in either quantitative indices (62% +/- 7% before grafting versus 58% +/- 6% after grafting) or qualitative indices (0.19 +/- 0.06 versus 0.17 +/- 0.06). However, in those segments with ischemic dysfunction before grafting, there was a significant increase in quantitative indices of regional wall motion after grafting (24% +/- 2% versus 50% +/- 5%; p less than 0.02). By contrast, qualitative indices continued to show no significant improvement (1.3 +/- 0.1 versus 1.05 +/- 0.2). We conclude that coronary artery bypass grafting significantly improves areas of ischemic regional wall dysfunction. These changes can be difficult to detect with visual qualitative methods and are best analyzed by techniques assessing changes in segmental wall thickness.

Transesophageal echocardiography. Preliminary results in patients with traumatic aortic rupture.

Eleven patients with blunt chest trauma at risk for traumatic aortic rupture underwent transesophageal echocardiography to image the descending aorta. Diagnoses were compared with the results of radiographic studies. Ten of the 11 patients underwent arch aortography, with positive results in six cases. In one patient, the results of a computed tomographic scan were interpreted as consistent with aortic rupture. The results of transesophageal echocardiography were positive for ruptured descending aorta in three of six patients with positive aortographic findings, and negative in eight patients. All three patients with positive findings had the diagnosis of ruptured descending aorta confirmed at surgery. The remaining eight patients demonstrated no aortic morbidity. These preliminary findings suggest that transesophageal echocardiography is a useful technique for the diagnosis of ruptured descending aorta following blunt chest trauma.

Detection of thrombotic cuspal obstruction of an aortic bioprosthesis with transesophageal echocardiography.

Bioprosthetic thrombotic obstruction is a rare complication which occurs relatively early after implantation. We present the transesophageal echocardiographic findings in a case of cuspal thrombosis of a Hancock aortic prosthesis which required valve replacement.

Color M-mode Doppler flow propagation velocity is a relatively preload-independent index of left ventricular filling.

Standard Doppler indexes of transmitral filling vary in response to alterations in left ventricular (LV) relaxation or preload. To determine whether color M-mode Doppler flow propagation velocity (vp), a new index of LV relaxation, is affected by preload, we obtained LV volumes, standard Doppler filling indexes, and vp in 20 patients at baseline, during Trendelenburg's position, inverse Trendelenburg's position, and after inhalation of amyl nitrite. LV end-diastolic volume decreased from 111 +/- 41 mL at baseline and 116 +/- 43 mL during Trendelenburg's position, to 104 +/- 40 during inverse Trendelenburg's maneuver and 92 +/- 33 mL after inhalation of amyl nitrite (P <.0001). Peak early filling velocity decreased from 79 +/- 19 cm/s and 90 +/- 20 cm/s to 73 +/- 22 cm/s and 64 +/- 20 cm/s, respectively (P < 0.0001). In contrast, no significant changes were found in vp (48 +/- 24 and 50 +/- 26 cm/s vs 48 +/- 25 and 48 +/- 25 cm/s). We conclude that vp is not affected significantly by preload. Thus vp may provide a more reliable and independent assessment of LV relaxation.

Amyloid goiter due to primary systemic amyloidosis: a diagnostic challenge.

We describe a euthyroid patient who presented with a goiter that continued to enlarge despite levothyroxine administration. Three fine-needle aspirations for cytology were nondiagnostic. An open biopsy was complicated by bleeding from the surgical site. Primary systemic amyloidosis was diagnosed on the basis of the goiter histology, bone marrow aspirate, and urine immunoelectrophoresis. The patient received melphalan and steroid treatment and survived for an additional 16 months. This period was complicated by congestive heart failure, generalized seizures, and upper gastrointestinal bleeding. Our case illustrates the difficulties in making the diagnosis and in treatment of primary systemic amyloidosis.

A hemodynamic comparison of Omniscience and Medtronic Hall aortic prostheses.

BACKGROUND AND AIMS OF THE STUDY: Preliminary reports have suggested hemodynamic disparities between single leaflet tilting disc prostheses. We tested the hypothesis that similarities in prosthetic design may not necessarily indicate hemodynamic equivalence. MATERIALS AND METHODS: In a retrospective analysis, we compared the functional characteristics of two single tilting disc (Omniscience and Medtronic Hall) prostheses implanted in the aortic position in 30 patients matched for valve size and left ventricular systolic function. RESULTS: Echocardiographic and Doppler analysis blinded to patient and valve type indicated similar quantitative left ventricular ejection fractions (64% +/- 6% for both) and cardiac outputs (4.8 +/- 1.2 vs. 4.6 +/- 1.2 l/min, p = 0.65) in the Onmiscience and Medtronic Hall groups, respectively. Transprosthetic instantaneous peak gradients were greater for Omniscience than for Medtronic Hall valves (44 +/- 8 vs. 35 +/- 11 mmHg, p < or = 0.02), as were the mean values (24 +/- 6 vs. 18 +/- 6 mmHg, p = 0.01). Even when 21 and 23 mm prostheses were analyzed separately to allow for unequal sewing ring diameters in the smallest valve sizes (Omniscience = 19 mm, Medtronic Hall = 20 mm), higher gradients were noted in the Omniscience prostheses. Effective orifice areas were smaller in the Omniscience than Medtronic Hall prostheses whether data from all prostheses (0.92 +/- 0.11 cm2 vs. 1.09 +/- 0.18 cm2, p < or = 0.05), or only data from 21 and 23 mm valves (0.94 +/- 0.11 cm2 vs. 1.10 +/- 0.18 cm2, p < 0.05) were included. Similarly, the dimensionless obstructive index, a parameter independent of left ventricular flow and annular size, was reduced in the Omniscience valves, indicating greater obstruction, whether all valves (0.31 +/- 0.04 vs. 0.36 +/- 0.07, p < or = 0.01) or only 21 and 23 mm valves (0.31 +/- 0.04 vs. 0.36 +/- .04, p < 0.001) were analyzed. CONCLUSION: Despite prosthetic design similarities, resting hemodynamic assessment indicates greater stenosis in Omniscience than Medtronic Hall valves when placed in the aortic position. The long term effects of these differences in terms of ventricular diastolic and systolic function and mass regression requires further evaluation.

Concomitant occurrence of a left atrial myxoma and an adenocarcinoma of the lung.

A 72-year-old previously healthy woman was found to have both a left atrial myxoma and a left lung mass during the evaluation for two cerebrovascular events. Resection of the atrial myxoma and a biopsy of the left lung mass were performed. Six weeks later she underwent a left upper lobectomy for adenocarcinoma of the lung. This case illustrates the concomitant occurrence of a left atrial myxoma and a primary lung cancer in a patient who underwent a successful staged treatment for both diseases.

Transesophageal echocardiographic evaluation of aortitis.

Aortitis is an uncommon infection which may occur in patients with preexisting atherosclerotic disease of the aorta. The clinical features in two patients presenting with fever and nonspecific symptoms are reviewed. In these patients, transesophageal echocardiographic features of wall thickening and false aneurysm formation were suggestive of the diagnosis of aortitis. Both patients were taken for surgical excision of the descending aorta and subsequently improved.