Defining normal variables of right ventricular size and function in pulmonary hypertension: an echocardiographic study.

BACKGROUND: Right ventricular (RV) fractional area change and tricuspid annular plane systolic excursion (TAPSE) are recognised methods for assessing RV function. However, the way in which these variables are affected by varying degrees of pulmonary hypertension (PH) has not been well characterised. METHODS: RV end-systolic area (RVESA), RV end-diastolic area (RVEDA), pulmonary artery systolic pressure (PASP) and TAPSE were collected from a database of 190 patients who had been referred to the PH clinic for evaluation. RESULTS: The mean (SD) age of the study population was 56 (17) years; 82 men were included with a mean (SD) PASP of 54 (33) mm Hg (range 16-150), RVESA of 14 (9) cm(2), RVEDA of 24 (9) cm(2), RV fractional area change of 44 (18)% and TAPSE of 2.06 (0.69) cm. Receiver-operating characteristic curves identified TAPSE <2.01 cm, RV fractional area change <40.9%, RVESA >12.3 cm(2) and RVEDA >23.4 cm(2) as abnormal values with PH. Finally stratification of patients into sub-groups according to their PASP allowed means and standard deviations to be reported for each echocardiographic variable. CONCLUSION: This analysis provides a range of normal variables of RV size and function, not previously published, that can be used in routine evaluation and follow-up of patients with PH.

Usefulness of the QTc interval in predicting myocardial ischemia in patients undergoing exercise stress testing.

Prolongation of the QTc interval during stress testing predicts myocardial ischemia with a sensitivity of 88% and a specificity of 93%. Measurement of the QTc segment should be considered as an adjunctive electrocardiographic variable in the interpretation of stress tests and is even useful in patients who are not able to achieve the age-predicted target heart rate level.

Thrombosis of mitral valve bioprostheses in patients requiring circulatory assistance.

Two patients with new mitral valve bioprostheses required implantation of Bio-Medicus centrifugal pumps (Bio-Medicus, Minneapolis, MN) for circulatory support and had evidence of prosthetic valve thrombosis 1 and 4 days later. Both patients died of thromboembolic complications despite surgical removal of the thrombus. Thrombosis is a rare early complication of bioprosthetic valves and in these cases was probably related to low transvalvular flow due to the use of circulatory assist devices. We discuss possible strategies for avoiding and managing this catastrophic complication.

Compression of a composite graft by a peri-aortic pseudoaneurysm in a postoperative Marfan patient.

A previously well 35-year-old female was referred to hospital with a four-week history of intermittent chest pain. She had a history of Marfan syndrome when she presented 11 years previously with aortic insufficiency and underwent replacement of the aortic root with a composite graft. Magnetic resonance examination of the chest and coronary angiography revealed an area of extraluminal flow posteromedially at the base of the aortic graft with no evidence of dissection. Transesophageal echocardiography clearly demonstrated the presence of a pseudoaneurysm that resulted from detachment of the left coronary artery from the graft, with intermittent compression of the aortic graft during systole. The patient underwent uneventful resection and replacement of the false aneurysm and patch repair of the left coronary artery. This unusual case illustrates the presence of a pseudoaneurysm as a result of detachment of the left coronary artery from a Dacron graft 11 years after a composite graft replacement.

Unusual accelerated progression of saccular aneurysms in an ectatic right coronary artery.

Localized aneurysmal dilation or ectasia of coronary arteries is a relatively uncommon angiographic finding, of which the pathophysiological mechanism remains speculative. The majority of patients diagnosed with this clinical entity usually present with angina pectoris. Furthermore, it is rare to find isolated ectasia or aneurysm dilation of the coronary arteries in patients with no prior history of coronary artery disease. The natural course is usually slowly progressive. This case demonstrates an unusual accelerated dilation of coronary saccular aneurysms, within a year of diagnosis, in a patient who presented with new onset congestive heart failure. Although the diagnosis was made with coronary angiography, both magnetic resonance imaging and transesophageal echocardiography were of critical diagnostic value to identify the size and extension of the aneurysms as well as the presence of intraluminal thrombi.

Pulmonary artery aneurysm: review and case report.

Aneurysms involving the main pulmonary artery and its branches are rare. Clinical experience is limited and current knowledge is mainly derived from autopsy findings. This case report describes a patient with a pulmonary artery aneurysm associated with a previous, partially corrected stenotic pulmonary valve. The patient presented with symptoms suggestive of aneurysm dissection three decades after commissurotomy. The diagnostic approach and therapeutic intervention are emphasized with a review of the literature.

Outpatient cardiac infusion units: impact in elderly patients with refractory heart failure.

BACKGROUND: The use of intermittent intravenous infusions of inotropic drugs is under evaluation in the management of patients with refractory heart failure. OBJECTIVES: We investigated the impact of intermittent outpatient infusions of inotropes on hospital admissions, emergency room visits, functional class, and symptom-free interval after administration of inotropes to elderly patients with advanced heart failure symptoms. METHODS: This retrospective analysis involved 24 elderly outpatients with a New York Heart Association class of III or IV and refractory heart failure symptoms. RESULTS: Seven patients with class III heart failure (age 74A+/-4 years; left ventricular ejection fraction 27A+/-9%) and 17 patients of class IV (age 73A+/-4 years; LVEF 21A+/-10%) were included. Twenty patients were males. A total of 365 outpatient treatment sessions were administered, with 15A+/-9 sessions per patient (range, 6-43). Eleven patients improved and were discharged; seven patients died; three discontinued treatment; two patients remain on therapy; and one patient required continuous infusion. During this treatment, there were only three emergency room visits and six hospital admissions due solely to heart failure. Fourteen patients required no emergency room visits or hospitalization. Of the patients discharged from the program, the interval without heart failure symptoms ranged from 60-356 days, with an improvement in NYHA class from 3.5A+/-0.6 to 1.4A+/-0.5 and no emergency room visits or hospital admissions. CONCLUSIONS: This type of therapy is well tolerated among elderly patients with refractory heart failure symptoms and its use deserves further investigation.

Assessing the aorta with transesophageal echocardiography. Update on imaging capabilities with today's technology.

Improved ultrasound imaging with transesophageal echocardiography is now readily available, so prompt, portable, convenient, and safe assessment of aortic disease is possible. The procedure offers a diagnostic approach that may be more useful and less expensive than other imaging studies. Many experts recommend transesophageal echocardiography as the procedure of choice in patients with possible aortic dissection, especially those who are in clinically unstable condition. Most patients can successfully undergo transesophageal echocardiography. The procedure is also an excellent method for evaluating the success of surgical repair of aortic dissection, and it can be used in long-term patient follow-up. Transesophageal echocardiography can assess atherosclerotic lesion size and composition, the dynamic effect of flow, and the aortic intima and lumen in evaluation of aortogenic embolization. It may help identify patients at high risk of stroke during cardiac surgery. In addition, the procedure is sensitive and specific in diagnosing penetrating aortic ulcers, which occur when an atheromatous lesion pierces the internal elastica and extends into the aortic wall media. The process may cause formation of intramural hematoma, identified on transesophageal echocardiography as homogeneous mottled thickening of the aortic wall and inward displacement of intimal calcification.

Intermittent infusion of inotropes in the outpatient setting: one-year post treatment analysis.

The course of patients with New York Heart Association (NYHA) class III and IV and refractory heart failure symptoms is characterized by progressive clinical deterioration and frequent hospital readmissions. The value of intermittent intravenous administration of inotropes in managing this group of patients in the outpatient setting has been controversial. In this study, patients with refractory heart failure symptoms were enrolled to assess the impact of a multidisciplinary outpatient program in terms of on hospital admissions, emergency room visits, and interval free of symptoms after administration of inotropes. This is a retrospective analysis on 41 patients with refractory heart failure treated at our outpatient cardiac infusion unit over a 20 month period. Thirteen patients with a NYHA class III [age 64 +/- 13; LVEF 27 +/- 9%] and 28 patients with a NYHA class IV [age 65 +/- 13 years; LVEF 21 +/- 9%], mostly males, were included. A total of 65 admissions for decompensated HF were recorded in the previous 6-months prior to initiation of the outpatient program; compared to only 4 emergency room visits and 7 hospital admissions after enrollment. Furthermore, 17 patients have been discharged with improvement in NYHA class from 3.5 +/- 0.6 to 1.4 +/- 0.5. On these patients, the interval free of symptoms since the last infusion treatment has ranged from 201 to 489 days, without emergency room visits or hospital admissions for congestive heart failure. The results of this study support the use of intermittent infusion of inotropes in the outpatient setting. Although the natural history for patients with refractory heart failure has been grim; the use of these intermittent infusions may in fact alter the natural course of end stage congestive heart failure patients and deserves further investigation.

In vitro exposure of murine macrophages to ultraviolet light induces apoptosis.

Ultraviolet light is a known exogenous stimuli with the ability to activate cell death by apoptosis. This study was done to examine the biologic effects of different energy levels of short wavelength UV light on cultured mouse macrophages. Cell proliferation, DNA content, and cellular ultrastructural architecture analysis demonstrated that ultraviolet light induces apoptosis in murine macrophages in culture. Exposure to 0.12J/cm2 evokes progressive cell demise with the classical features associated with apoptosis, whereas exposure to 5.0 J/cm2 results in extensive DNA degradation and crosslinking of cellular proteins. These two phenotypes are qualitatively described.

Differential strain and velocity generation along the right ventricular free wall in pulmonary hypertension.

BACKGROUND: In contrast to the homogeneously distributed deformation properties within the left ventricle, the right ventricular (RV) free wall (RVFW) shows a more inhomogeneous distribution. It has been demonstrated that pulmonary hypertension (PH) results in significant RVFW mechanical delay. OBJECTIVE: To assess the effect of the degree of pulmonary arterial systolic pressure on the RVFW strain gradient and on myocardial velocity generation. METHODS: Peak longitudinal strain and velocity data were collected from three different segments (basal, mid- and apical) of the RVFW in 17 normal individuals and 31 PH patients. RESULTS: A total of 144 RV wall segments were analyzed. RVFW strain values in individuals without PH were higher in the mid and apical segments than in the basal segment. In contrast, RVFW strain in PH patients was higher in basal segments and diminished toward the apex. In terms of RVFW velocities, both groups showed decremental values from basal to apical segments. Basal and mid-RVFW velocities were significantly lower in PH patients than in individuals without PH. CONCLUSIONS: PH results in significant alterations of strain and velocity generation that occurs along the RVFW. Of these abnormalities, the reduction in strain from the mid and apical RVFW segments was most predictive of PH. It is important to be aware of these differences in strain generation when studying the effect of PH on the right ventricle. Additional studies are required to determine whether these differences are due to RV remodelling.

Metabolic syndrome X: a comprehensive review of the pathophysiology and recommended therapy.

Diabetes mellitus is associated with a markedly increase prevalence of coronary artery disease, found to be as high as 55% (Lyons, 1993). The metabolic syndrome X, a multifaceted clinical entity produced by genetic, hormonal and lifestyle factors which occurs frequently in the general population, has been associated as an end point in patients with diabetes (Timar, Sestier et al., 2000). New data suggests that a clustering of truncal obesity, glucose intolerance or non-insulin dependent diabetes mellitus, dyslipidemia and essential hypertension are key components of this metabolic syndrome X (Timar, Sestier et al., 2000). In fact, the metabolic syndrome X has been shown to precede frank diabetes in a substantial number of patients; hence similar multiple cardiac risk factors will be found in this population. Thus, primary care providers should identify patients at an early stage so that appropriate treatment can be readily instituted. The goal of this review is to summarize criteria for diagnosis of patients with the metabolic syndrome X and therapeutic targets of each individual component is analyzed in a attempt to reduce cardiovascular events and improve clinical outcome based on the available clinical data.

Cholesterol feeding modulates spatial expression of TGF-beta 1 and beta 2 in aortas of Watanabe rabbits.

Several cytokines have been identified as markers of early atherosclerotic disease during vascular injury and remodelling. Of particular importance, transforming growth factor-beta (TGF-beta 1) has been found to be crucial in promoting connective tissue deposition resulting in both intimal and medial hyperplasia. However, the expression of TGF-beta 1 and beta 2 during cholesterol feeding in the Watanabe rabbit, an established model of hypercholesterolemia, has not been evaluated. Accordingly, we examined the expression of TGF-beta 1 and beta 2 signal from aortic segments of 10 heterozygous Watanabe rabbits with the use of reverse transcription-polymerase chain reaction (RT-PCR) amplification during normal non-supplemental diet and during 0.5% supplemental cholesterol feeding for a period of two months. TGF-beta transcripts from the aortic tissue were quantified at the end of the feeding interval. For Watanabe rabbits fed regular chow, the expression of both TGF-beta 1 and beta 2 is reduced in the aortic arch as compared with the descending aorta. In contrast, Watanabe rabbits fed high cholesterol diets manifested a differential expression of TGF-beta isoforms depending on the spatial location within the aorta. In the aortic arch, increased transcript signals for both TGF-beta 1 and beta 2 were noted as compared with rabbits on normal chow. The lesions found in the aortic arch are typified by abundant foam cells and proliferating smooth muscle cells. Analysis of the TGF-beta 1 and 2 profile on these same cell elements in vitro results in a similar expression of increased mRNA isoforms for TGF-beta 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Different temporal and spatial distribution of TGF-beta 1 and TGF-beta 2 in rabbit vascular tissue: potential role in normal vessel growth and maturation.

The expression of transforming growth factor beta 1 and beta 2 (TGF-beta 1 and beta 2) in aortic and venous tissue from male New Zealand White rabbits, at selected time intervals after birth, was examined by the reverse transcriptase polymerase chain reaction. Stable levels of TGF-beta 1 were found in all segments derived from the aortic arch and descending aorta at each time interval. However, increasing amounts of TGF-beta 2 transcripts were observed for the aortic arch from day 4, with peaks occurring between 1 and 6 months of age, followed by progressively decreasing levels thereafter. TGF-beta 2 transcripts in the descending aorta generally did not change significantly over time. TGF-beta transcripts manifested a significantly lower expression in the vena cava than in aortic segments. Histological analysis of the vascular tissue showed cellular hyperplasia (2.5-fold greater prevalence of nuclei per field) in the aortic arch media at 1 month of age as compared with nuclei per field at 12 months and increasing thickness of the aortic arch media with time. No significant differences in relative collagen concentrations were observed among the aortic and vena cava segments. These results suggest that these TGF-beta isoforms may participate in the physiological induction and differentiation of arterial and venous tissue during early normal vascular maturation.

Cholesterol transport function of pancreatic cholesterol esterase: directed sterol uptake and esterification in enterocytes.

We have recently hypothesized that neutral lipids can, in part, move across biological membranes via a mechanism involving enzymes anchored to membrane proteoglycans such as those found in the brush border of the enterocyte [Bosner, M. S., Gulick, T., Riley, D. J. S., Spilburg, C. A., & Lange, L. G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7438-7442]. Present results now show a subsequent, essential protein-mediated sorting of neutral lipids for further intracellular metabolism. Thus, in the absence of enzyme, 0.002 pmol of cellular ester appeared after 2 h, and its level increased only 3.5-fold after 12 h. However, in the presence of cholesterol esterase, the level of cholesterol ester increased 39-fold in the same time period, indicating that the enzyme-mediated uptake accounts for 10-fold greater ester synthesis than that from basal absorption. Kinetic analysis reveals that both enzyme-mediated and background absorption depend on taurocholate concentration and are second-order reactions more likely dependent on collision than diffusion. Other lipid-recognizing proteins such as pancreatic triglyceride lipase and the intestinal fatty acid binding protein are not stimulatory to intracellular cholesterol processing. Taken together, these data suggest that pancreatic cholesterol esterase and possibly other proteoglycan-binding extracellular enzymes of neutral lipid metabolism may facilitate movement of neutral lipids into the plasma membrane and direct them into functional intracellular sites.