A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Abnormal left ventricular filling with increasing age reflects abnormal myocardial characteristics independent of ischemia or hypertrophy

Abnormal left ventricular (IV) filling may occur with increasing age despite apparently normal IV size and function, and is usually attributed to IV hypertrophy and coronary artery disease. The purpose of this study was to determine whether myocardial abnormalities could be identified in 67 such patients (36 men, mean age 57 +/- 9 years) whose IV hypertrophy and coronary artery disease were excluded by dobutamine echocardiography. All patients underwent gray scale and color tissue Doppler imaging from 3 apical views, which were stored and analyzed off line. Disturbances in structure and function were assessed by averaging the cyclic variation of integrated backscatter, strain rate, and peak systolic strain from each myocardial segment. Calibrated integrated backscatter (corrected for pericardial backscatter intensity) was measured in the septum and posterior wall from the parasternal long-axis view. Abnormal IV filling was present in 36 subjects (54%). Subjects with and without abnormal IV filling had similar IV mass, but differed in age (p <0.01), cyclic variation (p = 0.001), strain rate (p <0.01), and peak systolic strain (p <0.001). Multivariate logistic regression analysis demonstrated that age (p = 0.016) and cyclic variation (p = 0.042) were the most important determinants of abnormal IV filling in these apparently normal subjects. (C) 2003 by Excerpta Medica, Inc.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

Independent contribution of plaque complexity to myocardial ischemia during Dobutamine stress echocardiography

The influence of complex plaque morphology on the extent of demand-induced ischemia in unselected patients is not well defined. We sought to investigate the functional significance of lesion morphology in patients who underwent coronary angiography and dobutamine stress echocardiography (DSE).,Angiography and DSE were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients. Angiographic assessments involved quantification of stenosis severity, assessment of the extent of jeopardized myocardium, and categorization of plaque morphology according to the Ambrose classification. DSE was interpreted by separate investigators with respect to wall motion score index (WMSI) and number of coronary territories involved. A general linear model was constructed to assess,the independent contribution of patient characteristics and angiographic and DSE results with respect to extent of ischemic myocardium. Complex lesion morphology was seen in 62 patients (32%). Patients with complex lesions were more likely to have had prior myocardial infarction (p < 0.001) and be current smokers (p = 0.03). During angiography, they exhibited a trend toward a greater number of diseased vessels, had a greater coronary jeopardy score (p < 0.001) and more frequent collateral flow (p = 0.03). During echocardiography, patients had a higher stress WMSI (p < 0.001) and were more likely to show ischemia in all 3 arterial territories (p < 0.01). On multivariate regression, the coronary artery jeopardy score and the presence of complex plaque morphology were independent predictors of the extent of ischemic myocardium (R 2 = 34%, p < 0.001). Thus, patients with complex plaque morphology are older, more likely to smoke, and more likely to have had prior myocardial. infarction. They exhibit more extensive disease with higher coronary jeopardy scores and a higher resting and peak stress WMSI. Despite these differences, complex plaque morphology remains an independent predictor of the extent of ischemia during stress. (C) 2003 by Excerpta Medica, Inc.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Miringosclerose em pacientes com insuficiência renal crônica: análise comparativa com um grupo controle

A miringoesclerose é uma alteração cicatricial da lâmina própria da membrana timpânica caracterizada por proliferação de fibras colágenas, seguida de hialinização, deposição de cálcio e fósforo, seguindo uma seqüência semelhante ao que ocorre em outros tipos de calcificação patológica comuns em pacientes com doença renal crônica. OBJETIVO: Verificar a influencia da insuficiência renal crônica (IRC) na prevalência da miringoesclerose. MÉTODO: Foi realizada otoscopia em 341 pacientes com IRC em hemodiálise e em 356 indivíduos de um grupo controle. Foi comparada a freqüência de otoscopia positiva entre os dois grupos, procurando-se relacionar com variáveis pessoais e relacionadas a IRC. RESULTADOS: O grupo de pacientes apresentou 11,7% de otoscopia positiva contra 5,1% do grupo controle. Não houve influência do sexo ou cor na freqüência da miringoesclerose. Porém, os grupos foram heterogêneos em relação à faixa etária. Também não houve diferença importante no tempo de diálise nem nos níveis séricos de minerais e do PTH entre os pacientes do grupo de estudo que apresentavam otoscopia positiva ou negativa. CONCLUSÃO: Os achados, embora apontem para uma maior ocorrência da miringoesclerose nos pacientes renais crônicos, não nos permitem concluir com certeza que exista alguma relação entre a IRC e as alterações timpânicas.

Validation of percutaneous puncture trajectory during renal access using 4D ultrasound reconstruction

Background: An accurate percutaneous puncture is essential for disintegration and removal of renal stones. Although this procedure has proven to be safe, some organs surrounding the renal target might be accidentally perforated. This work describes a new intraoperative framework where tracked surgical tools are superimposed within 4D ultrasound imaging for security assessment of the percutaneous puncture trajectory (PPT). Methods: A PPT is first generated from the skin puncture site towards an anatomical target, using the information retrieved by electromagnetic motion tracking sensors coupled to surgical tools. Then, 2D ultrasound images acquired with a tracked probe are used to reconstruct a 4D ultrasound around the PPT under GPU processing. Volume hole-filling was performed in different processing time intervals by a tri-linear interpolation method. At spaced time intervals, the volume of the anatomical structures was segmented to ascertain if any vital structure is in between PPT and might compromise the surgical success. To enhance the volume visualization of the reconstructed structures, different render transfer functions were used. Results: Real-time US volume reconstruction and rendering with more than 25 frames/s was only possible when rendering only three orthogonal slice views. When using the whole reconstructed volume one achieved 8-15 frames/s. 3 frames/s were reached when one introduce the segmentation and detection if some structure intersected the PPT. Conclusions: The proposed framework creates a virtual and intuitive platform that can be used to identify and validate a PPT to safely and accurately perform the puncture in percutaneous nephrolithotomy.