A novel method for quantitative myocardial contrast echocardiography in mice.

The small size of the mouse heart frequently imparts technical challenges when applying conventional in vivo imaging methods for assessing heart function. Here, we describe the use of high-frequency ultrasound imaging in conjunction with a size-tuned blood pool contrast agent for quantitatively assessing myocardial perfusion in living mice. A perflurocarbon microbubble formulation exhibiting a narrow size distribution was developed, and echogenicity was assessed at 18 MHz in vitro. Adult mice were subjected to permanent ligation of the left anterior descending artery. Ultrasound imaging was performed on day 7, and a cohort of intact mice was used as a control. Parasternal long-axis cine clips were acquired at 18 MHz before and after contrast administration. Reduced ejection fraction and increased end-systolic volume were observed in infarcted compared with control mice. In control animals, washin of the contrast agent was visible in all myocardial segments. Reduced contrast enhancement was observed in apical-posterolateral regions of all infarcted mice. A novel method for reslicing of the imaging data through the time domain provided a two-dimensional presentation of regional contrast agent washin, enabling convenient identification of locations exhibiting altered perfusion. Myocardial segments exhibiting diminished contractility were observed to have correspondingly low relative myocardial perfusion. The contrast agent formulation and methods demonstrated here provide the basis for simplifying routine in vivo estimation of infarct size in mice and may be particularly useful in longitudinal evaluation of revascularization interventions and assessment of peri-infarct ischemia. NEW & NOTEWORTHY Murine myocardial contrast echocardiography frequently suffers from poor sensitivity to contrast. Here, we formulated a novel size-tuned microbubble contrast agent and validated it for use with ultra-high-frequency ultrasound. A novel data method for evaluating myocardial perfusion based on reslicing the imaging data through the time domain is presented.

Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy.

Although cytoskeletal mutations are known causes of genetically based forms of dilated cardiomyopathy, the pathways that link these defects with cardiomyopathy are unclear. Here we report that the alpha-actinin-associated LIM protein (ALP; Alp in mice) has an essential role in the embryonic development of the right ventricular (RV) chamber during its exposure to high biomechanical workloads in utero. Disruption of the gene encoding Alp (Alp) is associated with RV chamber dilation and dysfunction, directly implicating alpha-actinin-associated proteins in the onset of cardiomyopathy. In vitro assays showed that Alp directly enhances the capacity of alpha-actinin to cross-link actin filaments, indicating that the loss of Alp function contributes to destabilization of actin anchorage sites in cardiac muscle. Alp also colocalizes at the intercalated disc with alpha-actinin and gamma-catenin, the latter being a known disease gene for human RV dysplasia. Taken together, these studies point to a novel developmental pathway for RV dilated cardiomyopathy via instability of alpha-actinin complexes.

Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.

BACKGROUND: Mutations in the transforming growth factor beta receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. METHODS: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. RESULTS: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. CONCLUSION: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

Histone deacetylase inhibitors interrupt HSP90•RASGRP1 and HSP90•CRAF interactions to upregulate BIM and circumvent drug resistance in lymphoma cells.

Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here, we show that trichostatin A, romidepsin and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen-activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo. Importantly, these pro-apoptotic effects are mimicked by RASGRP1 small interfering RNA (siRNA) or HSP90 inhibition and reversed by overexpression of constitutively active MEK1 or siRNA-mediated downregulation of BIM. Collectively, these observations not only identify a new HSP90 client protein, RASGRP1, but also delineate a complete signaling pathway from HSP90 acetylation through RASGRP1 and CRAF degradation to BIM upregulation that contributes to selective cytotoxicity of HDAC inhibitors in lymphoid malignancies.

Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.

BACKGROUND: Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases of disease in the cardiomyopathic (CM) hamster, and the combination of GH with chronic ACE inhibition was assessed in late-phase heart failure. METHODS AND RESULTS: CM hamsters (CHF 147 line) at 4 months showed severe systolic left ventricular (LV) dysfunction with normal LV filling pressure, and at 10 months there was more severe systolic as well as diastolic dysfunction with increasing myocardial fibrosis. Recombinant human GH alone for 3 weeks at age 4 months increased LV wall thickness and reduced systolic wall stress without altering diastolic wall stress, whereas at 10 months, wall stress and fractional shortening did not improve. The LV dP/dt(max) was enhanced at both ages by GH, which at 4 months reflected increased contractility, but at 10 months was most likely caused by elevation of the LV filling pressure. The increasing degree of fibrosis correlated inversely with LV function but was unaffected by GH. In other CM hamsters, high-dose ACE inhibition alone (quinapril), started at 8 months and continued for 11 weeks, improved LV function and inhibited unfavorable remodeling, but the addition of GH for 3 weeks at age 10 months produced increased wall thickness with little additional functional benefit and increased the LV filling pressure and diastolic wall stress. CONCLUSIONS: GH treatment alone improved LV dysfunction at 4 months of age in CM hamsters by increasing contractility and reducing wall stress but had few beneficial effects at 10 months in severe LV failure. After chronic ACE inhibition, addition of GH at 10 months had no additional beneficial effects and further increased LV diastolic pressure. These differing effects of GH may relate to the progressive increase of LV fibrosis in the CM hamster.

Densitometric regional ejection fraction: a new three-dimensional index of regional left ventricular function--comparison with geometric methods.

Densitometric regional ejection fraction obtained by computer analysis of digital subtraction ventriculography was evaluated as a new, quantitative, three-dimensional index of regional left ventricular performance. Eighteen patients with coronary artery disease and seven control subjects had right anterior oblique ventriculography at rest and immediately after rapid atrial pacing using central venous injection of contrast material. Regional left ventricular ejection fraction was determined by densitometry in six segments drawn around the end-diastolic center of gravity, and compared with two conventional indexes of segmental wall motion: area and radial regional ejection fraction. Densitometric, area or radial regional ejection fraction was classified as abnormal if it fell at least 2 standard deviations below the corresponding mean value in the normal group. The densitometric method did not require outlining of the end-systolic left ventricular silhouette and was the easiest and fastest to perform of all three techniques. In addition, intra- and interobserver reproducibilities were higher with the densitometric method (r = 0.97 and 0.95) than with either the area (r = 0.84 and 0.82) or the radial method (r = 0.82 and 0.76). Regional left ventricular dysfunction as assessed by the densitometric, area and radial techniques allowed the detection of coronary artery disease in 50, 50 and 44% of the patients at rest and in 83, 67 and 61% of the patients in the post-pacing period, respectively. Post-pacing regional left ventricular dysfunction accurately predicted the presence or absence of greater than 70% diameter stenosis in the supplying coronary artery in 75, 67 and 56% of the cases, respectively. Thus, densitometric analysis of digital subtraction ventriculography allows a fast and reproducible three-dimensional determination of regional left ventricular ejection fraction. Using this technique, pacing-induced regional dysfunction can be detected in most patients with coronary artery disease and corresponds well with the location of significant coronary artery lesions.

Role of intraaortic balloon pump counterpulsation in high risk coronary rotational atherectomy.

OBJECTIVES: This study sought to evaluate the role of intraaortic balloon pump counterpulsation in preventing hemodynamic instability and promoting a successful outcome during percutaneous transluminal coronary rotational atherectomy in high risk patients. BACKGROUND: The application of rotational atherectomy has widened to include patients with complex lesions and left ventricular dysfunction. Although intraaortic balloon pumping has been successfully used to provide hemodynamic support during balloon angioplasty, its role in high risk rotational atherectomy has not yet been defined. METHODS: In a retrospective review of 159 consecutive high risk patients who underwent rotational atherectomy, 28 had an intraaortic balloon pump placed electively before the procedure (Group 1) whereas 131 did not (Group 2). RESULTS: Group 1 was older and more likely to have multivessel disease and left ventricular dysfunction. Augmented diastolic pressure was maintained > 90 mm Hg in all Group 1 patients, and significant procedure-related hypotension was encountered in nine Group 2 patients, requiring an emergency intraaortic balloon pump in five. Procedural success was achieved in all 28 patients in Group 1 and in 118 in Group 2 (p = 0.07). Slow flow occurred in 18% and 17% of Group 1 and 2 patients, respectively. Among patients with slow flow, non-Q wave myocardial infarction occurred only in Group 2 (0% vs. 27%). On multivariate analysis, elective intraaortic balloon pump placement was the only variable to correlate with a successful procedure uncomplicated by hypotension (p < 0.05). Hospital stay and vascular complications were similar in both groups. CONCLUSIONS: Elective placement of an intraaortic balloon pump before coronary rotational atherectomy in selected high risk patients promotes both procedural hemodynamic stability and a successful outcome.

Atheroma morphology and distribution in proximal left anterior descending coronary artery: in vivo observations.

OBJECTIVES: This study sought to examine, in vivo, the shape and position of atheroma in the proximal left anterior descending coronary artery. BACKGROUND: The prevalence, shape and location of atheromas involving the proximal left anterior descending artery have implications regarding the role of disturbed shear forces in the genesis of atherosclerosis. However, no data are available regarding in vivo findings or advanced disease. METHODS: Forty-two consecutive high quality intravascular ultrasound images were examined from patients with atherosclerotic disease in the proximal left anterior descending artery just distal to the left main bifurcation. Lesion percent area stenosis and maximal, minimal and flow divider intimal-medial thickness were measured at the region immediately after the circumflex takeoff. The angle formed by the midpoint of the flow divider, the human center of gravity and the maximal plaque thickness were determined. RESULTS: Eccentricity of vessel wall atheroma was observed such that the maximal wall thickness (1.42 +/- 0.50 mm [mean +/- SD]) differed significantly from minimal wall thickness (0.17 +/- 0.098 mm). Further, the region of vessel wall manifesting maximal thickness was greater than the flow divider thickness (0.26 +/- 0.16 mm). Maximal plaque thickness spared the region of the flow divider in 100% of cases and was positioned at a mean angle of 193 +/- 49 degrees from the center of the flow divider. Eccentric morphology was maintained across the 24% to 80% range of area stenosis. CONCLUSIONS: Atheromas in the very proximal left anterior descending artery are located opposite the circumflex takeoff, spare the flow divider and maintain eccentricity across a wide range of vessel stenoses. These in vivo morphologic data support the potential role of fluid dynamic mechanical factors in atherogenesis and have implications regarding the success of catheter-based interventional procedures at the site.

Early changes of right heart geometry after pulmonary thromboendarterectomy.

To determine the changes in right heart hemodynamics and geometry early after surgery for chronic pulmonary hypertension due to large vessel thromboembolic occlusion, 30 patients were evaluated 8 +/- 8 days (mean +/- SD) before and 6 +/- 4 days after pulmonary thromboendarterectomy by two-dimensional echocardiography and right heart catheterization. Surgery resulted in an early significant improvement in hemodynamic variables including mean pulmonary artery pressure (48 +/- 12 to 28 +/- 8 mm Hg, p less than 0.001), right ventricular systolic pressure (76 +/- 20 to 47 +/- 15 mm Hg, p less than 0.001), pulmonary vascular resistance (935 +/- 620 to 278 +/- 252 dynes.s.cm-5, p less than 0.001) and cardiac index (2.0 +/- 0.5 to 2.9 +/- 0.6 liters/min per m2, p less than 0.001). Similarly, echocardiographic variables of right heart structures, which were well outside the normal range preoperatively, improved significantly early after thromboendarterectomy. These included diameters of the pulmonary artery (2.8 +/- 0.3 to 2.4 +/- 0.4 cm, p less than 0.001), inferior vena cava (2.9 +/- 0.6 to 2.2 +/- 0.4 cm, p less than 0.001) and right atrium (6.8 +/- 1.5 to 5.9 +/- 1.5 cm, p less than 0.001) as well as right ventricular short axis (4.5 +/- 0.8 to 3.7 +/- 0.8 cm, p less than 0.001) and long axis (8.7 +/- 0.9 to 8.1 +/- 0.9 cm, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise hemodynamics during long-term implantation of a left ventricular assist device in patients awaiting heart transplantation.

OBJECTIVES: The goal of this study was to assess patients with end-stage heart disease after implantation of a left ventricular assist device at rest and during exercise compatible with activities of daily life. BACKGROUND: Mechanical circulatory assistance with a left ventricular assist device is an accepted therapy for bridging patients with end-stage heart disease to heart transplantation and has been proposed for long-term implantation. METHODS: Three patients (aged 37, 42 and 57 years) with end-stage heart failure required implantation of a pneumatically driven, asynchronous Thermedics left ventricular assist device while awaiting heart transplantation. All were assessed 1 month later during graded supine bicycle exercise (maximal work load 100 to 150 W). Detailed central hemodynamics, including continuous pulmonary artery oxygen saturation and oxygen consumption measurements, were obtained. Two of the patients also underwent upright treadmill exercise with oxygen consumption measurements. RESULTS: During supine bicycle exercise, the heart rate increased from 93 +/- 37 beats/min (95% confidence interval: mean +/- t0.025 x SE) at rest to 119 +/- 54 beats/min and left ventricular assist device rate increased from 82 +/- 47 to 109 +/- 55 beats/min. Oxygen consumption increased from 3.0 +/- 0.9 to 8.7 +/- 2.9 ml oxygen/min per kg body weight. Cardiac output increased from 6.0 +/- 4.4 to 9.6 +/- 7.1 liters/min, yielding an average exercise factor of 8.5 +/- 7.7 and an exercise index of 0.83 +/- 0.61. The patients assessed during treadmill exercise achieved a maximal oxygen consumption of 14.3 and 16.7 ml of oxygen/min per kg. No thromboembolic or other complications attributable to left ventricular assist device implantation occurred during the duration of support. All patients survived orthotopic heart transplantation and are doing well. CONCLUSIONS: Significant work loads compatible with activities of daily life and adequate exercise hemodynamics were demonstrated by these patients while awaiting heart transplantation. Definitive conclusions regarding the use of this device must be viewed as preliminary because only three patients were involved in this study and the failure rate may be as high as 71% (95% confidence interval of left ventricular assist device success as a bridge to transplantation 29.3% to 100%). Final conclusions regarding the safety and efficacy of the left ventricular assist device as a possible long-term circulatory support device must await results of larger multicenter trials in progress.

Familial aortic dissecting aneurysm.

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.

Heterogeneity of vasomotor response to acetylcholine along the human coronary artery.

OBJECTIVES: In view of the segmental occurrence of coronary atherosclerosis, we postulated that acetylcholine may cause heterogeneous vasomotion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. BACKGROUND: Previous studies have reported that acetylcholine causes constriction of atherosclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angiographically detectable disease. METHODS: We developed algorithms to quantitate the dimensions of a single coronary artery over virtually its entire length during a control state and during graded doses of intracoronary acetylcholine. On the basis of triplicate control angiograms, the limit of detection of a change from control diameter was 0.31 mm (> or = 2 SD). RESULTS: Analysis of multiple segments (each 5.6 +/- 1.1 [mean +/- SD] mm) along a single coronary artery revealed a heterogeneous response to acetylcholine in 27 of 31 patients at the 10(-4) mol/liter dose and in 29 of 31 patients when responses at 10(-6), 10(-5) and 10(-4) mol/liter doses were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequency of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10(-4) mol/liter dose. Inducible vasomotion was observed as far distally as 7.3 cm from the site of acetylcholine infusion. CONCLUSIONS: Response to intracoronary acetylcholine with mild coronary disease is heterogeneous; disparate dimensional responses may occur in different segments of the same vessel. Inclusion of all analyzable regions of a coronary artery and the use of a reproducibility limit for quantitative angiography are optimal for assessment of segmental coronary vasomotion.

Quantitative assessment of segmental wall motion abnormalities at rest and after atrial pacing using digital intravenous ventriculography.

Digital intravenous ventriculography lends itself readily to quantitative assessment of ventricular wall motion with computer algorithms. Forty-five patients referred for cardiac catheterization were studied by digital intravenous ventriculography (mask mode) and direct ventriculography in the 30 degrees right anterior oblique position. Quantitative wall motion was analyzed by a radial shortening method applied to both studies. Lower limits of normal radial shortening were determined for each technique and used to determine the presence or absence of wall motion disorders. The inter- and intraobserver variability of radial shortening measurements was +/- 5.3 and +/- 8.8%, respectively, with maximal discrepancies of -6 and +7% fractional shortening units. The overall agreement between the two techniques in wall motion assessment was 87% (274 of 315 radii). A subset of patients also underwent atrial pacing, and a second digital intravenous ventriculogram was obtained (5 normal subjects and 15 patients with coronary artery disease). Although analysis of wall motion at rest showed a poor sensitivity for detection of significant coronary stenoses, nine of nine patients with coronary artery disease and normal wall motion at rest showed a quantitative decrease in radial wall motion after atrial pacing. Thus, digital intravenous ventriculograms can be used to provide quantitative wall motion analyses that show a high degree of agreement with those of standard, direct left ventriculography. Atrial pacing can be used to increase the sensitivity of wall motion analysis for the detection of significant coronary disease.

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.

OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

The influence of coronary collateral flow on the assessment of myocardial perfusion by videodensitometry.

OBJECTIVES: Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been quantitatively validated. METHODS: A distal coronary arterial collateral path was created into the left anterior descending coronary artery (LAD) bed in 8 anesthetized pigs. Both LAD and collateral paths were pump-perfused and corresponding flows measured. A number of commonly used digital indices and parametric images of myocardial perfusion were then extracted from the sequence of images filmed before and during the injection of contrast. Data were acquired at 5 levels of total flow (LAD flow + collateral flow): 100, 85, 70, 55 and 40% of maximally vasodilated, baseline flow. At each level of total flow, data were acquired at 4 levels of collateral flow ratios (collateral flow/total flow): 0, 10, 25 and 50%. RESULTS: Regional percent segment shortening, reflecting myocardial blood flow, decreased as total flow fell, and remained unaltered when coronary collateral ratio alone was altered without change in total flow. On the other hand, linear regression between total flow and digital indices at 10, 25 and 50% coronary collateral flow ratios, compared with 0%, showed a successive and significant downward displacement, documenting an underestimation of flow by all digital indices in the presence of collateral flow. CONCLUSIONS: In the absence of a collateral pathway and during maximal coronary vasodilation with adenosine, digital radiographic indices of myocardial perfusion, based upon indicator dilution theory, show a relatively good correlation with regional transmural myocardial blood flow. However, due to underestimation of total transmural blood flow, these indices have limited utility when myocardial perfusion is provided in part by a collateral pathway. The effect is probably related to an alteration in the regional vascular volume into which iodinated contrast is injected.

Reliability of echocardiographic and electrocardiographic parameters in assessing serial changes in left ventricular mass.

A reliable noninvasive index of left ventricular mass would be useful in following patients with valvular heart disease and left ventricular hypertrophy. We reviewed concurrent electrocardiograms and echocardiograms from 54 subjects, 39 patients with aortic or mitral valve disease and 15 normal subjects. Pre- and early postoperative echocardiographic estimates of left ventricular mass in 17 patients who had valve replacements correlated well (r = 0.96, p less than 0.001) and demonstrated little change in mean values despite altered left ventricular dimensions. Echocardiographic estimates of left ventricular mass were, therefore, used as a standard for evaluating other noninvasive indices. Precordial electrocardiographic voltage showed a weak correlation with left ventricular mass in the study group as a whole (r = 0.59, p less than 0.001), but no correlation in patients with volume overload (r = 0.36, p = NS). In 18 patients who had preoperative and three separate postoperative studies at least eight weeks apart, changes in left ventricular cross-sectional area (an index of left ventricular mass which corrects for changes in left ventricular volume) closely followed alterations in left ventricular mass. However, changes in posterior wall and interventricular septal thickness often resulted from altered ventricular volume and did not accurately reflect directional changes in left ventricular mass. Serial changes in electrocardiographic voltage were similarly unreliable. We conclude that left ventricular mass and cross-sectional area by echocardiography allow accurate noninvasive assessment of left ventricular mass, whereas wall thickness and electrocardiographic changes do not.

The utility of an in-hospital observation period after discontinuing intravenous antibiotics.

PURPOSE: To determine whether observing patients overnight in the hospital after intravenous antibiotics have been discontinued is a useful way to identify important clinical events. SUBJECTS AND METHODS: We performed a retrospective chart review of patients admitted during a 6-month period to a tertiary care teaching hospital with a primary diagnosis of either pneumonia, urinary tract infection, or cellulitis who were treated with intravenous antibiotics. Charts were abstracted for patient characteristics, including comorbid illnesses and laboratory values, as well as for evidence of recurrent infection or other adverse events. RESULTS: Of the 374 patients in the study, 63 (17%) were discharged on the day intravenous antibiotics were discontinued. These patients were 10 years younger (P = 0.0009) and had fewer comorbid illnesses (P = 0.02) than those who were observed in the hospital. Recurrent infection was noted in 3 (1%; 95% confidence interval 0.2% to 3%) of the 308 patients who were observed. A mild adverse antibiotic reaction was also noted in three observed patients. The readmission rate to the same institution for recurrent infection was 3% for patients with an observation period and 2% for patients without an observation period (P = 0.70). CONCLUSIONS: Observing patients overnight in the hospital after discontinuing intravenous antibiotics is a common clinical practice. There was an extremely low incidence of adverse events during the observation period, and the events that did occur would have been discovered in an outpatient setting. In-hospital observation after discontinuing intravenous antibiotics is unnecessary for most patients with pneumonia, urinary tract infection, or cellulitis and greatly increases health-care costs.

Catheter-based intravascular ultrasound imaging of chronic thromboembolic pulmonary disease.

Pulmonary thromboendarterectomy is now the treatment of choice for pulmonary hypertension due to chronic pulmonary thromboemboli. A precise assessment of location and extension of these thrombi is important because only proximal chronic pulmonary thromboemboli are accessible to surgery. Because intravascular ultrasound imaging can assess not only arterial luminal size, but also wall thickness, its value as a complement to angiography was assessed in 11 patients aged 35 to 64 years with severe pulmonary hypertension (systolic pulmonary artery pressure, mean +/- standard deviation 70 +/- 19 mm Hg; pulmonary artery resistance, 609 +/- 297 dynes.s.cm-5). Intravascular ultrasound was obtained in 10 of 11 patients and no complication occurred. Intravascular ultrasound identified 10 segments with suspected chronic pulmonary thromboemboli in 7 patients, all confirmed at operation. Nine segments were considered normal, all of which (except 1) were free of chronic pulmonary thromboemboli at operation. Image quality was highly dependent on pulmonary artery size and position of the catheter. Therefore, intravascular ultrasound of pulmonary arteries is feasible and safe in patients with pulmonary hypertension. It may help to assess the location and extension of the pathologic process involving pulmonary arteries.

Quantitative angiography of coronary artery dimensions 24 hours after rotational atherectomy.

Rotational atherectomy results in platelet activation and heat generation, which may impact artery size immediately after treatment. In addition, arteries treated with balloon angioplasty may exhibit recoil within 24 hours. In this study, arteries treated with rotational atherectomy, with and without adjunctive balloon angioplasty, were analyzed by quantitative coronary angiography to determine the effect of rotational atherectomy on the dynamic behavior of the arterial wall within 24 hours after the procedure. Quantitative coronary angiography was performed at a core laboratory. Coronary angiogram acquisitions were preceded by intracoronary nitroglycerin injections and were repeated using identical angles of projection. Proximal and distal reference vessel diameters were 2.55 +/- 0.60 and 2.28 +/- 0.51 mm, respectively, and did not change from pre- to postprocedure. Both were larger the following day increasing to 2.72 +/- 0.65 and 2.52 +/- 0.52 mm, respectively, (p <0.001). Minimum luminal diameter (MLD) increased from 0.70 +/- 0.28 mm before to 1.49 +/- 0.34 mm after the procedure and to 1.72 +/- 0.37 mm at 24-hour follow-up (p <0.001). Subset analysis of patients treated with rotational atherectomy alone or rotational atherectomy with adjunctive balloon angioplasty revealed that the increase in luminal diameters occurred in both subsets. Patients treated with adjunctive angioplasty had a smaller initial MLD, a larger postprocedure MLD, and no difference in MLD at 24-hour follow-up compared with stand-alone rotational atherectomy. Subset analysis of 100 patients who had 6-month follow-up angiography revealed that both a calculated acute gain and chronic late loss, based on a 24-hour film, differed significantly from values using a film acquired immediately after the procedure. However, the slope of the linear regression between acute gain and chronic late loss did not differ. Coronary arteries treated with rotational atherectomy with or without adjunctive balloon angioplasty increase significantly in size during the first 24 hours after the procedure. This phenomenon has implications for the calculation of absolute gain and chronic late loss, but not for the linear relation between the 2 quantitative outcomes.

Effects of atrial pacing on global and regional left ventricular function in coronary heart disease assessed by digital intravenous ventriculography.

Digital i.v. ventriculography in conjunction with rapid atrial pacing was used to assess the effects of ischemic stress on global and regional function in 22 patients referred for cardiac catheterization (5 had normal coronary arteries and 17 had greater than 70% diameter reduction of at least 1 major coronary artery). End-diastolic, end-systolic and stroke volume indexes and the ejection fraction were determined by an area-length technique from the mask mode images before and after pacing. In addition, segmental responses were quantitated using a radial shortening method. Subjects with normal coronary arteries showed no overall change in the postpacing volume or ejection fraction indexes. Coronary patients showed no overall change in postpacing end-diastolic volume (86 +/- 25 ml/m2 at control vs 90 +/- 31 ml/m2 after pacing, difference not significant), but there was a significant increase in end-systolic volume (25 +/- 15 ml/m2 at control vs 32 +/- 18 ml/m2 after pacing, p less than 0.005) and a decrease in ejection fraction (72 +/- 11% at rest vs 64 +/- 18% after pacing, p less than 0.025). Furthermore, quantitative deterioration in wall motion was seen in 14 of 17 coronary patients (82%) and in none of the normal patients. Analysis of segmental wall motion was the most sensitive diagnostic variable. A combination of atrial pacing stress testing and digital i.v. ventriculography is useful in detecting functionally significant coronary disease through quantitation of global and regional dysfunction which does not require arterial cannulation.