Estimating the real-world performance of the PROMISE minimal-risk tool.

BACKGROUND: Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes. METHODS: We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored. RESULTS: Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless. CONCLUSION: The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.

Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy.

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Cardiovascular abnormalities in transgenic mice with reduced brown fat: an animal model of human obesity.

BACKGROUND: A new model of murine obesity has recently been developed through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined. METHODS AND RESULTS: Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85+/-1 versus 66+/-2 mm Hg; P<0.01), left ventricular dilation and hypertrophy (mass/body weight 4.0+/-0.2 versus 2.7+/-0.3 mg/g; P<0.01), and high cardiac output (cardiac index 3.2+/-0.4 versus 2.4+/-0.1 mL x kg(-1) x min(-1); P<0.01). Baseline functional parameters assessed in vitro were not different, but after imposition of zero-flow ischemia, significant relaxation impairment developed in obese mice. Although morphometrically determined myocyte diameters were similar, the percentage of interstitial fibrosis was significantly increased in transgenic mice compared with wild-type controls (7.5+/-2% versus 4. 2+/-0.2%; P<0.01). CONCLUSIONS: Transgenic ablation of brown adipose tissue is associated not only with obesity but also with systemic hypertension, left ventricular hypertrophy with eccentric remodeling and fibrosis, and high cardiac output, a unique constellation of findings strikingly similar to that seen in human obesity. Mice with reduced brown fat may serve as a new model for the cardiovascular morbid complications associated with obesity in humans.

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure.

BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension.

To examine the relations among hypertrophy, fibrosis and diastolic performance in early experimental hypertension, 18 control dogs and 12 dogs with experimental left ventricular hypertrophy were studied. Diastolic function was impaired in dogs with left ventricular hypertrophy, with decreased Doppler early to atrial inflow velocity ratio (E/A) (1.35 versus 1.72), increased atrial filling fraction (35% versus 29%), decreased sonomicrometric peak rates of wall thinning (-2.01 versus -3.37 liters/s) and filling (4.33 versus 6.64 liters/s) and prolonged time constant of isovolumetric relaxation (tau; 34.3 versus 28.1 ms). Neither chamber stiffness (k; P = AekV) nor passive elastic stiffness (E; E = k sigma, where sigma = stress) was increased. At postmortem examination, the hypertensive left ventricle weighed significantly more than normal (116 versus 80 g; p less than 0.01) and had greater muscle fiber diameter at endocardial and epicardial sampling sites in the apical free wall, basal free wall and septum (mean diameter 50 +/- 8 microns in hypertensive dogs, 37 +/- 8 microns in normal dogs; p less than 0.01). In contrast, neither percent fibrosis (1.2 +/- 0.8 versus 0.9 +/- 0.6 in normal dogs) nor fibrotic volume (1.21 +/- 0.63 versus 0.72 +/- 0.42%/g in normal dogs) was significantly increased. Peak volumetric filling rate was inversely related to fiber diameter (r = -0.74, p less than 0.001), although no variable of left ventricular function was significantly related to percent or volume fibrosis (all r less than 0.60, all p greater than 0.05). Thus, diastolic dysfunction may exist in the setting of hypertrophy without significant fibrosis. Increased myocyte size was associated with early diastolic filling abnormalities characteristic of the hypertensive left ventricle. Fibrosis appears to be a less important determinant of diastolic performance.

Atrial ejection force: a noninvasive assessment of atrial systolic function.

OBJECTIVES: The purpose of this study was to define atrial ejection force and to develop a method for its noninvasive measurement from echocardiographic data. BACKGROUND: Assessment of diastolic function through measurement of the components of ventricular filling has largely neglected the vigor of atrial systole, in part because this has been difficult to quantify. However, atrial ejection force, defined as that force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, can be assessed noninvasively by combined two-dimensional imaging and Doppler echocardiography. This index of atrial function, based on classic newtonian mechanics, provides a physiologic assessment of atrial systolic function. METHODS: To evaluate the usefulness of atrial ejection force, we studied the return of left atrial ejection force in 29 patients after elective cardioversion for atrial fibrillation. Transmitral Doppler inflow patterns at rest were assessed immediately after cardioversion and at 24 h, 1 week, 1 month and > 3 months later. A healthy adult group (n = 10) served as control subjects. RESULTS: After successful cardioversion, atrial ejection force was significantly depressed compared with that in the control group (5.2 +/- 6.8 vs. 16.3 +/- 4.7 kdynes; p < 0.0001). Over successive weeks, atrial ejection force improved in the subgroup of patients who remained in sinus rhythm (n = 18), whereas no improvement was seen during the period of maintained sinus rhythm in the patients with subsequent reversion to atrial fibrillation (n = 11). CONCLUSIONS: Atrial ejection force provides a physiologic assessment of atrial systolic function and is a potentially useful index for assessing atrial contribution to diastolic performance. In patients who successfully underwent cardioversion from atrial fibrillation, atrial ejection force improved over several weeks only in the subgroup in which sinus rhythm was maintained.

Clinical utility of transthoracic two-dimensional and Doppler echocardiography.

OBJECTIVES: The purpose of this study was to determine the value of contemporary echocardiography for patient diagnosis and management in clinical practice. BACKGROUND: Although the use of echocardiography is growing rapidly, there is little information about its clinical utility. METHODS: A prospective observational study was performed at a community-based, tertiary care teaching hospital. Physicians were interviewed before and after learning the result of their patients' echocardiographic examination. Chart reviews were performed to confirm reports of new diagnoses and treatments that resulted from echocardiography. RESULTS: Physician interviews were successfully completed for 244 (49%) of 497 inpatients and 101 (30%) of 336 outpatients. Among patients with moderate or greater mitral regurgitation, the diagnosis of "clinically significant" mitral regurgitation was unsuspected in 5 (31%) of 16 outpatients and 28 (60%) of 47 inpatients. Among the patients with left ventricular wall motion abnormalities, the result was unsuspected in 7 (50%) of 14 outpatients and 18 (22%) of 81 inpatients. As assessed by chart review, echocardiography produced a definite new diagnosis in 25 inpatients (10%) and 5 outpatients (5%) and was responsible for changes in pharmacologic treatment in at least 16 inpatients (7%) and 2 outpatients (2%). CONCLUSIONS: The echocardiogram commonly provided information that was unexpected. This information provided a definite new diagnosis or treatment in a smaller proportion of the patients. Further research is necessary to define the appropriate yield that would warrant echocardiography on the basis of both clinical and cost-effectiveness criteria.

Echocardiographic visualization of coronary artery anatomy in the adult.

In the light of technologic advances and the development of new imaging planes, the feasibility of two-dimensional echocardiographic visualization of coronary artery anatomy was reevaluated in the adult. Thirty-five subjects were studied using an ultrasonograph equipped with a 3.5 and 5.0 MHz annular array transducer, digital processing and cine loop review. There were 18 normal subjects and 17 patients with heart disease, including 9 patients with valvular, 5 patients with coronary, 2 patients with congenital and 1 patient with cardiomyopathic disease. The mean age was 47 +/- 18 years (range 17 to 79). Modifications of standard parasternal and apical views permitted high quality images of portions of each of the major epicardial vessels adequate for assessment of luminal diameter. The left main coronary artery was seen in 30 (86%) of the 35 subjects and its bifurcation was seen in 15. The left anterior descending coronary artery was seen in 30 subjects (mean length 3.9 +/- 2.3 cm, maximal length 7.5), the left circumflex artery in 11 (1.1 +/- 1.0, maximal 3.0) and the right coronary artery in 32 (5.6 +/- 2.6, maximal 12). Proximal and mid portions of the left anterior descending artery were seen in 23 and 11 subjects, respectively. The average proximal length visualized was 4.2 cm, and the average luminal diameter visualized was 4.9 mm. The average length of the mid left anterior descending coronary artery seen was 1.9 cm and the average luminal diameter seen was 4.6 mm. The proximal right coronary artery was seen in 17 subjects (average visualized length 2.7 cm and average diameter 3.1 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in diastolic function in response to progressive left ventricular hypertrophy.

To examine the time course of the functional consequences of progressive left ventricular hypertrophy, diastolic left ventricular inflow and wall thinning variables were analyzed in 13 dogs before and 2, 4, 8 and 12 weeks after creation of perinephritic hypertension. Left ventricular echocardiograms were digitized for dimensions, mass and peak rates of wall thinning (-dh/dt/h) and cavity enlargement (dD/dt/D). Doppler recordings of left ventricular inflow were analyzed for peak early (E) and late (A) diastolic inflow velocities, their ratio and atrial filling fraction. At 2 weeks, systolic blood pressure increased from 151 to 233 mm Hg, wall stress from 52 to 80 kdynes/cm2 and posterior wall thickness from 0.68 to 0.84 cm (all p less than 0.05). Left ventricular mass increased from 90 to 115 g over 12 weeks (p less than 0.05). Heart rate, cavity size and systolic shortening were unchanged at all data points. Diastolic abnormalities accompanied the developing hypertrophy and included impairment of early function, as demonstrated by a peak rate of wall thinning, from -13.4 to -8.9 l/s at 2 weeks (p less than 0.05), increased dependence on atrial systolic filling, a decrease in E/A from 1.68 to 1.29 at 4 weeks (p less than 0.05) and an increase in atrial filling fraction from 30% to 43% at 8 weeks (p = NS). Thus, diastolic dysfunction is an early consequence of experimental left ventricular hypertrophy. Different aspects of diastolic impairment are sensitively reflected by echocardiographic Doppler recordings, suggesting that these methods should be useful for the detection of diastolic dysfunction in human patients.

Two-dimensional and Doppler echocardiographic determinants of the natural history of mitral valve narrowing in patients with rheumatic mitral stenosis: implications for follow-up.

Fifty patients with rheumatic mitral stenosis were studied with serial two-dimensional and Doppler echocardiography to determine the natural history of changes in mitral valve area and its relation to transmitral gradients and mitral valve morphology. Over the 39-month observation period (range 7 to 74 months) the decline in valve area was 0.09 +/- 0.21 cm2/year. In addition, there were significant increases in total echocardiographic score (p = 0.0001), severity of mitral anulus calcification (p = 0.05) and severity of mitral regurgitation (p = 0.0007). Patients with an echocardiographic score greater than or equal to 8 had a more progressive course. In addition, patients with a more progressive course (decline in valve area greater than or equal to 0.1 cm2/year) had a significantly greater initial mean gradient (p = 0.01), peak gradient (p = 0.007) and total echocardiographic score (p = 0.0008). Initial valve area did not correlate with the rate of stenosis progression. Of 22 patients with an echocardiographic score less than 8 and a peak mitral gradient less than 10 mm Hg, only 1 patient (5%) had a more progressive course, compared with 80% of those with a total echocardiographic score greater than or equal to 8 and a gradient greater than or equal to 10 mm Hg. The rate of mitral valve narrowing in individual patients with rheumatic mitral stenosis is variable. Patients whose valve disease progresses rapidly are those with a greater mitral valve echocardiographic score and higher peak and mean transmitral gradients.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term captopril treatment improves diastolic filling more than systolic performance in rats with large myocardial infarction.

OBJECTIVES: This study sought to determine the effects of long-term angiotensin-converting enzyme (ACE) inhibition on left ventricular (LV) diastolic filling in postinfarction heart failure. BACKGROUND: Long-term treatment with ACE inhibitors is beneficial in experimental animals and patients with heart failure. Because this treatment typically produces only small improvements in LV systolic function, we hypothesized that improvements in LV diastolic filling might contribute to the overall beneficial effects of ACE inhibitors after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in rats 1 and 6 weeks after transmural MI or sham operation. Rats with MI were randomized to no treatment (n = 10) or captopril (2 g/liter in drinking water, n = 8) after the baseline echocardiogram. RESULTS: Six weeks after MI, untreated rats had significant LV dilation compared with sham-operated rats (LV diastolic dimension [mean+/-SEM] 10.7 +/- 0.3 vs. 8.5 +/- 0.3 mm, p < 0.05). Rats with untreated MI also had impaired fractional shortening (9 +/- 1% vs. 34 +/- 2%, p < 0.05) and depressed systolic thickening of the noninfarcted posterior wall (3% +/- 3% vs, 65 +/- 9%, p < 0.05). Rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. At 6 weeks, peak early filling velocity (E) was increased (97 +/- 3 vs. 77 +/- 2 cm/s, p < 0.05), E wave deceleration was more rapid (23 +/- 3 vs. 12 +/- 1 m/s2, p < 0.05), isovolumetric relaxation time was decreased (18 +/- 1 vs. 24 +/- 1 ms, p < 0.05), and late filling velocity was lower (26 +/- 7 vs. 34 +/- 1 cm/s, p < 0.05) in rats with MI versus sham-operated rats. Compared with rats with untreated MI, rats receiving captopril had similar LV diastolic dimensions (10.5 +/- 0.35 vs. 10.7 +/- 0.35 mm), slightly higher fractional shortening (16 +/- 2% vs. 9 +/- 1%, p < 0.05 [captopril MI vs. untreated MI]) and unchanged posterior wall thickening (49 +/- 12% vs. 37 +/- 3%, p = 0.3). In contrast, captopril almost completely normalized diastolic filling abnormalities (E velocity 82 +/- 5 cm/s, p < 0.05 [captopril MI vs. untreated MI]; E wave deceleration rate 15 +/- 2 m/s2, p < 0.05 [captopril MI vs. untreated MI]; isovolumetric relaxation time 20 +/- 1 ms). CONCLUSIONS: Long-term captopril treatment in rats with a large MI modestly limits LV remodeling and the development of systolic dysfunction but markedly improves the restrictive diastolic filling abnormalities that are seen in untreated rats.

Different effects of prolonged exercise on the right and left ventricles.

To examine the functional consequences of the greater increase in right ventricular work with exercise, the effects of prolonged exercise on the right and left heart chambers were compared in 41 athletes before, at the finish (13 min) and after recovery (28 h) from the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike ride, 42.2 km run). Two-dimensional and Doppler echocardiograms were analyzed for left and right atrial and ventricular areas at end-diastole and end-systole, right and left ventricular inflow velocities and mitral and tricuspid regurgitation. After exercise, left ventricular and left and right atrial sizes were reduced, whereas right ventricular size increased (diastole: 21.4 to 24.2 cm2; systole: 15.8 to 18.2 cm2; p less than 0.01). The emptying fraction of all chambers was unchanged. Left but not right ventricular inflow showed an increase in peak velocity of rapid filling, whereas both atrial systolic velocities increased (26 to 38 cm/s tricuspid; 38 to 54 cm/s mitral; both p less than 0.01). Overall, the right ventricular early to atrial velocity ratio was reduced after exercise (1.56 to 1.17; p less than 0.05) and the left ventricular pattern was unchanged. The prevalence of tricuspid regurgitation was statistically unchanged (86% to 52%), although that of mitral regurgitation was greatly reduced (76% to 0%). Changes in all variables returned toward prerace values during recovery. Thus, in highly trained athletes, prolonged exercise causes differing responses of the right and left ventricles. These differences may be due to changes in right ventricular function, shape or compliance.

Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy.

Because idiopathic dilated cardiomyopathy is characterized by elevated wall stress and a more spherical left ventricle, the relations among shape, afterload and survival were examined. Thirty-six patients with cardiomyopathy were prospectively studied by two-dimensional echocardiography. Data included echocardiographic short- and long-axis cavity dimensions, their ratio and, with cuff systolic blood pressure, meridional and circumferential end-systolic stress and their ratios. Survivors (n = 16) were followed up for 52 months (range 40 to 76); nonsurvivors (n = 20) died an average of 11 months after study. Survivors had a smaller left ventricular end-diastolic short-axis dimension (6.4 versus 7.1 cm, p less than 0.03) but a similar long-axis length (8.6 versus 8.3 cm). However, overall cavity shape or the ratio of short- to long-axis end-diastolic dimensions was more spherical in those with poorer survival (ratio 0.76 versus 0.68, p less than 0.02). Meridional and circumferential end-systolic stresses were similar in the two groups, but stress was more evenly distributed in the long- and short-axis planes in nonsurvivors (meridional/circumferential stress ratio 0.57 versus 0.52 in survivors, p less than 0.05). Improved survival was associated with an end-diastolic short-axis dimension less than 7.63 cm, a short- to long-axis ratio less than 0.76 and a meridional to circumferential stress ratio less than 0.54. Life table analysis revealed a 28% mortality rate in patients with all three of these characteristics compared with 100% in patients with none. Survivors and nonsurvivors did not differ in systolic cavity dimension, wall thickness, relative wall thickness, cavity volume, percent posterior wall thickening or fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5-year study.

OBJECTIVES: We sought to validate the safety of transesophageal echocardiographically guided early cardioversion in conjunction with short-term anticoagulation as a strategy for guiding early cardioversion in hospitalized patients with atrial fibrillation. BACKGROUND: Because atrial thrombi are poorly seen by conventional imaging techniques, several weeks of prophylactic anticoagulation is routinely prescribed before cardioversion. Transesophageal echocardiography is a superior test for identifying atrial thrombi; preliminary feasibility studies have supported its use to guide early cardioversion for patients in whom no thrombus is observed, but safety has not been validated in any large series. METHODS: All patients admitted to hospital with atrial fibrillation during a 4.5-year period were screened. The inclusion criterion was a clinical duration of atrial fibrillation > 2 days or of unknown duration. Patients received anticoagulation with heparin/warfarin and underwent conventional transthoracic echocardiography followed by transesophageal study. Patients in whom transesophageal echocardiography revealed no atrial thrombus underwent pharmacologic or electrical cardioversion followed by warfarin therapy for 1 month. Cardioversion was deferred in patients with evidence of atrial thrombi, and they received prolonged warfarin treatment. RESULTS: Two hundred thirty-three patients (86% of those eligible) agreed to participate, and 230 underwent transesophageal echocardiography. Transesophageal echocardiography identified 40 atrial thrombi (left atrium 34, right atrium 6) in 34 patients (15%). One hundred eighty-six (95%) of 196 patients without thrombi had successful cardioversion to sinus rhythm, all without prolonged anticoagulation, and none (0%, 95% confidence interval 0% to 1.6%) experienced a clinical thromboembolic event. Eighteen patients with atrial thrombi underwent uneventful cardioversion after prolonged anticoagulation. CONCLUSIONS: Compared with smaller series that have shown only feasibility, this large prospective and consecutive study of patients undergoing transesophageal echocardiographically facilitated early cardioversion in conjunction with short-term anticoagulation validates the safety of this strategy. This treatment algorithm has a safety profile similar to conventional therapy and minimizes both the period of anticoagulation and the overall duration of atrial fibrillation.

Comparison of echocardiographic methods for assessment of left ventricular shortening and wall stress.

M-mode echocardiographic measurement of left ventricular fractional shortening and meridional wall stress has been used extensively alone and in combination to describe left ventricular systolic function. To determine whether the improved dimensional information afforded by two-dimensional echocardiography might result in shortening and stress calculations yielding a different view of left ventricular function, we compared two-dimensional and M-mode echocardiograms in 69 subjects (19 normal, 13 with aortic stenosis, 22 with aortic regurgitation and 15 with congestive cardiomyopathy). Fractional shortening was greater with M-mode than with two-dimensional echocardiography in all subjects, especially in those with cardiomyopathy (p less than 0.05). In aortic stenosis, two-dimensional shortening, at 24 +/- 5%, was reduced (p less than 0.05 versus normal), but M-mode shortening, at 34 +/- 5%, was not. M-mode estimates of meridional stress were higher than two-dimensional values, again especially in cardiomyopathy. Two-dimensional echocardiography enabled determination of long- and short-axis ratios, circumferential stress and the ratio of circumferential to meridional stresses. Circumferential stress was elevated in aortic stenosis at 302 +/- 65 X 10(3) dynes/cm2, suggesting afterload excess as the cause for the observed reduction in two-dimensional shortening. The more spherical cardiomyopathic hearts had a meridional to circumferential stress ratio closer to 1, such that use of meridional stress alone would overestimate effective afterload. It is concluded that M-mode and two-dimensional echocardiographic analyses of left ventricular shortening and stress produce different results. Two-dimensional echocardiographic methods may enhance the assessment of ventricular function, especially in patients with aortic stenosis and cardiomyopathy.

Creatinine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy.

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 microgram/kg per min), used to increase heart rate x systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p less than 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac morphology and function in senescent rats: gender-related differences.

OBJECTIVES: We sought to better understand the effects of aging and gender on left ventricular (LV) structure and function. BACKGROUND: Cardiovascular disease in older persons is associated with increased mortality and morbidity. The influence of gender on age-related cardiac changes is incompletely characterized. METHODS: We studied 34 senescent, male and female, normotensive Fischer rats with transthoracic Doppler echocardiography and morphometric and histopathologic analyses. RESULTS: Male rats were larger (396 +/- 31 g vs. 282 +/- 35 g), and LV mass in males was greater (1.04 +/- 0.22 g vs. 0.67 +/- 0.13 g). However, wall and chamber dimensions normalized to body weight revealed proportionately thicker anterior and posterior walls in females. Relative wall thickness ratio (2 [Diastolic posterior wall thickness]/Diastolic LV internal chamber diameter) was greater in females, but abnormal fractional shortening and diastolic filling (E/A ratio) patterns were more common in males. Significant mitral regurgitation (MR) was sevenfold more common among males (88% vs. 12%, p < 0.001). Histopathologic analysis showed that the cardiac myocytes were larger, and there was greater LV fibrosis in males (both p < 0.001). CONCLUSIONS: Gender-related morphologic and functional differences are important to consider in cardiovascular assessment. Very old rats show significant gender differences in LV size and function. Male rat hearts are larger, thinner and more fibrotic and have indexes of diminished performance. The high prevalence of MR in male rats may play a crucial role in these gender differences.