New insights towards catheter-based identification of vulnerable plaque

Sudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensity of atherosclerotic lesions to provoke clinical events. Most of these events are related to plaque rupture and subsequent thrombotic occlusion at the site of non-flow limiting atherosclerotic lesions in epicardial coronary arteries. Detection of these non-obstructive, lipid rich, high-risk plaques may have an important impact on the prevention of acute myocardial infarction and sudden death. Currently, there are several intravascular tools capable of locally evaluating determinants of plaque vulnerability such as the size of the lipid core, thickness of the fibrous cap, inflammation within the cap and positive remodeling. These new modalities have the potential to provide insights into the pathophysiology of the natural history of coronary plaque by means of prospective studies.     

In vivo validation of an experimental adaptive quantitative coronary angiography algorithm to circumvent overestimation of small luminal diameters

The reliability of quantitative coronary angiography (QCA) measurements is of fundamental importance for the study and practice of interventional cardiology. In vivo validation results have consistently reported a tendency for QCA systems to overestimate small luminal diameters. Such a systematic error may result in the underestimation of luminal gain during intracoronary procedures and in the underestimation of progression of coronary artery disease during longitudinal studies. We report the in vivo validation results of an experimental adaptive edge-detection algorithm that was developed to reduce overestimation of small luminal diameters by incorporating a dynamic function of variable kernel size of the derivative operator and variable weighting of the first and second derivatives of the brightness profile. The results of the experimental algorithm were compared to those of the conventional parent edge detection algorithm with fixed parameters. Dynamic adjustment of the edge-detection algorithm parameters was found to improve measurements of small (lt;0.8-mm) luminal diameters as evidenced by an intercept of +.07 mm for the algorithm with variable weighting compared to +0.21 mm for the parent algorithm with fixed weighting. A slope of <1 was found for both the parent and experimental algorithms with subsequent underestimation of large luminal diameters. Systematic errors in a QCA system can be identified and corrected by the execution of objective in vivo validation studies and the consequent refinement of edge-detection algorithms. The overestimation of small luminal diameters may be overcome by the incorporation of a dynamic edge-detection algorithm. Further refinements in edge-detection algorithms will be required to address the issue of underestimation of large luminal diameters before the absolute values derived from QCA measurements can be considered accurate over the full range of clinically encountered luminal diameters. © 1995 Wiley-Liss, Inc.     

Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction.

OBJECTIVES: Among patients undergoing aortic valve surgery for chronic aortic regurgitation (AR), we sought to: 1) compare survival among those with and without severe left ventricular dysfunction (LVD); 2) identify risk factors for death, including LVD and date of operation; and 3) estimate contemporary risk for cardiomyopathic patients. BACKGROUND: Patients with chronic AR and severe LVD have been considered high risk for aortic valve surgery, with limited prognosis. Transplantation is considered for some. METHODS: From 1972 to 1999, 724 patients underwent surgery for chronic AR; 88 (12%) had severe LVD. They were propensity matched to patients with nonsevere LVD to compare hospital mortality, interaction of operative date with severity of LVD, and late survival. Propensity score-adjusted multivariable analysis was performed for all 724 patients to identify risk factors for death. RESULTS: Survival was lower (p = 0.04) among patients with severe LVD than among matched patients with nonsevere LVD (30-day, 1-, 5-, and 25-year survival estimates were 91% vs. 96%, 81% vs. 92%, 68% vs. 81%, and 5% vs. 12%, respectively). However, survival of patients with severe LVD improved dramatically across the study time frame (p = 0.0004): hospital mortality decreased from 50% in 1975 to 0% after 1985, and time-related survival in patients with severe LVD operated on since 1985 became equivalent to that of matched patients with nonsevere LVD (p = 0.96). CONCLUSIONS: Neutralizing risk of severe LVD has improved early and late survival such that aortic valve surgery for chronic AR and cardiomyopathy is no longer a high-risk procedure for which transplantation is the best option.     

Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration

The vascular adventitia is emerging as an important modulator of vessel remodeling. Adventitial myofibroblasts migrate to the neointima after balloon angioplasty, contributing to restenosis. We postulated that angiotensin II (Ang II) enhances adventitial myofibroblast migration in vitro via reduced nicotinamide-adenine dinucleotide phosphate oxidase-derived H(2)O(2) and that Nox4-based oxidase promotes migration. Ang II increased myofibroblast migration in a concentration-dependent manner, with a peak increase of 1023+/-83%. Rat adventitial myofibroblasts were cotransfected with human Nox4 and human p22-phox plasmids or an empty vector. PCR showed an 8-fold increase in human Nox4 and human p22-phox plasmid expression. Using RT-PCR with primers specifically designed for rat reduced nicotinamide-adenine dinucleotide phosphate oxidases, endogenous Nox levels were determined. Ang II decreased endogenous Nox4 and Nox1 mRNA to 41% and 27% of control, respectively, but had no effect on Nox2. Cotransfection with human Nox4 and human p22-phox plasmids combined with Ang II reduced endogenous Nox4 mRNA levels (37+/-5% of control; P<0.05), whereas it had no significant effect on Nox1 or Nox2. In empty vector-transfected cells, Ang II increased myofibroblast migration by 192+/-32% versus vehicle (P<0.01) while increasing H(2)O(2) (473+/-22% versus control; P<0.001). Cotransfection with human Nox4 and human p22-phox plasmids decreased Ang II-induced migration (46+/-6%; P<0.001) in parallel with attenuation of H(2)O(2) production (23+/-8% versus empty vector; P<0.05). Our data suggest that Nox4 promotes Ang II-induced myofibroblast migration via an H(2)O(2)-dependent pathway. The data also suggest that Nox4 causes feedback inhibition of its own expression in adventitial myofibroblasts.     

Microalbuminuria in a population-based study of diabetes.

The prevalence of microalbuminuria in younger-onset diabetic participants in a large population-based study of diabetic retinopathy was determined, and the relationships of microalbuminuria to blood pressure and other risk factors were investigated. Using an agglutination inhibition test (AlbuScreen), the frequency of microalbuminuria was 21.2%. To evaluate the association of several characteristics with the presence of microalbuminuria, multivariate models based on logistic regression were developed. Microalbuminuria was associated with having higher systolic or diastolic blood pressure and higher glycosylated hemoglobin. These findings give further impetus to efforts to reduce controllable risk factors in younger-onset diabetic persons.     

Spontaneous rupture of the spleen in chronic calcifying pancreatitis: report of three cases

Spontaneous rupture of the spleen is a rare complication of chronic calcifying pancreatitis. Anemia and hemorrhagic shock may not occur, making diagnosis more difficult. Favourable response to conservative treatment does not prevent the need for splenectomy, as calcifiying chronic pancreatitis may progress locally. We report three cases of spontaneous rupture of the spleen. In two cases, splenic rupture revealed calcifying chronic pancreatitis and both patients underwent urgent splenectomy. In the third case, the patient was known to have calcifying chronic pancreatitis, and splenectomy was performed because of unsuccessful conservative treatment. We discuss the role of distal pancreatectomy during splenectomy to reduce the rate of postoperative complications and additional surgery. We also discuss the role of arterial embolisation and laparoscopy in the management of this rare condition.     

Discrepancy between simultaneous digital skin microvascular and brachial artery macrovascular post-occlusive hyperemia in systemic sclerosis

OBJECTIVE: Vascular impairment, a main feature of the pathogenesis of systemic sclerosis (SSc), involves both the macro- and the microvasculature. We compared and correlated simultaneously measured skin microvascular and brachial artery macrovascular post-occlusive hyperemia in 3 groups: patients with SSc, patients with primary Raynaud's phenomenon (RP), and healthy volunteers. METHODS: Thirty-three healthy volunteers, 36 patients with primary RP, and 42 patients with SSc were enrolled. For each subject, brachial artery flow-mediated dilation (FMD) and cutaneous post-occlusive reactive hyperemia (PORH) were simultaneously recorded after 5-minute occlusion of the brachial artery. Local thermal hyperemia, nitroglycerin-mediated dilation (NMD), intima-media thickness (IMT), and pulse wave velocity (PWV) were also assessed. RESULTS: Digital cutaneous peak PORH was altered in patients with primary RP and SSc compared to healthy controls, whereas FMD was not significantly different among all groups. We observed a correlation between digital peak cutaneous vascular conductance and brachial FMD in healthy controls (r = 0.49; p = 0.004), but not in patients with primary RP or SSc. Thermal hyperemia was altered only in patients with SSc. Brachial NMD, IMT, and PWV were not different among all groups. CONCLUSION: We observed a loss of the correlation between brachial FMD and digital cutaneous PORH in patients with SSc and primary RP. Microvascular function is impaired in SSc, whereas brachial artery endothelial function is normal.     

Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the DeltaE47 neurophysin mutation

Postmortem examinations of the hypothalamus of patients with autosomal dominant neurohypophyseal diabetes insipidus (adNDI), which have been reported only on persons dying between the ages of 37-87 yr, reveal the presence of the arginine vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the expected AVP-producing magnocellular neurons. To determine whether the clinical course of adNDI is compatible with the hypothesis that the neuropathologic findings are attributable to a progressive loss of magnocellular neurons beginning in early life, we performed posterior pituitary magnetic resonance imaging and water deprivation tests, including plasma ACTH measurements, on 17 affected members of a kindred with the deltaE47 neurophysin mutation whose ages ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr) underwent these tests as controls. All six children undergoing magnetic resonance imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of nine affected adults showed an absent or barely visible PPHS, whereas eight of nine age-matched nonaffected adults produced a normal size PPHS. During water deprivation tests, infants concentrated their urine normally, and a 3-month-old infant produced a high plasma AVP level of 15.7 pmol/liter. By school age, affected children were no longer able to concentrate their urine or prevent hypernatremia. Affected adults became dehydrated; their median plasma AVP level was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P = 0.008). These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.     

Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis.

Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four randomised seven day treatment periods in which they received only pancreatic supplement (Pancrelipase, 27 capsules per day) or supplement plus cimetidine (20 mg/kg body weight/24 h) or sodium bicarbonate (15 g/m2/24 h) alone or in combination. Dietary intake was not fixed but was restricted to foods of known fat and nitrogen content from which daily intakes could be computed. Faecal fat and nitrogen were calculated as g/24 h and percentage of intake. Addition of either cimetidine or bicarbonate resulted in significant improvement in fat and nitrogen excretion, which was not greater with the combination of both drugs. Cimetidine and sodium bicarbonate in these doses are therefore sufficient to produce maximal improvement in digestive activity of pancreatic supplements. Fat excretion per gram of intake fell with cimetidine and bicarbonate from 12 times the normal level, to normal, in patients consuming less than 120 g fat daily. Above this intake the dose of pancreatic supplement appeared to be inadequate. Faecal nitrogen excretion increased with nitrogen intake in all four periods, but, in contrast with fat excretion, the response to cimetidine and bicarbonate was not affected by the level of intake. Dietary intake appears to be a significant factor in determining the faecal output of fat and nitrogen in patients with pancreatic insufficiency and should be considered when determining the optimum amount of pancreatic supplementation.