Vasopressin administration facilitates fluid removal during hemodialysis.

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Predictors of hemorrhage in patients with untreated brain arteriovenous malformation.

BACKGROUND: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. METHODS: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. RESULTS: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. CONCLUSIONS: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study.

BACKGROUND: Few population-based studies with long-term follow-up have compared risk of recurrent stroke and cardiac events after first ischemic stroke. The relative risk of these two outcomes may inform treatment decisions. METHODS: In the population-based Northern Manhattan Study, first ischemic stroke patients age 40 or older were prospectively followed for recurrent stroke, myocardial infarction (MI), and cause-specific mortality. Fatal cardiac events were defined as death secondary to MI, congestive heart failure, sudden death/arrhythmia, and cardiopulmonary arrest. Risk of events (with 95% CIs) was calculated using Kaplan-Meier survival analysis and adjusted for sex and age using Cox proportional hazard models. RESULTS: Mean age (n = 655; median follow-up 4.0 years) was 69.7 +/- 12.7 years. The risk of recurrent stroke was more than twice that of cardiac events (including nonfatal MI) at 30 days and approximately twice cardiac risk at 5 years. The age- and sex-adjusted 5-year risk of fatal or nonfatal recurrent stroke was 18.3% (14.8 to 21.7%), and the 5-year risk of MI or fatal cardiac event was 8.6% (6.0 to 11.2%). The adjusted 5-year risk of nonfatal stroke (14.8%, 11.6 to 17.9%) was approximately twice as high as fatal cardiac events (6.4%, 4.1 to 8.6%) and four times higher than risk of fatal stroke (3.7%, 2.1 to 5.4%). CONCLUSIONS: Cardiac mortality is nearly twice as high as mortality owing to recurrent stroke, but long-term risk of all stroke, fatal or nonfatal, is approximately twice the risk of all cardiac events. The high risk of nonfatal recurrent stroke reinforces the importance of therapies aimed at preventing stroke recurrence in addition to preventing cardiac events.

Relative elevation in baseline leukocyte count predicts first cerebral infarction.

BACKGROUND: Atherosclerosis is an inflammatory disease, and leukocyte levels are associated with future risk of ischemic cardiac disease. OBJECTIVE: To investigate the hypothesis that relative elevations in leukocyte count in a stroke-free population predict future ischemic stroke (IS). METHODS: A population-based prospective cohort study was performed in a multiethnic urban population. Stroke-free community participants were identified by random-digit dialing. Leukocyte levels were measured at enrollment, and participants were followed annually for IS, myocardial infarction (MI), and cause-specific mortality. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for IS, MI, and vascular death after adjustment for medical, behavioral, and socioeconomic factors. RESULTS: Among 3,103 stroke-free community participants (mean age 69.2 +/- 10.3 years) with baseline leukocyte levels measured, median follow-up was 5.2 years. After adjusting for stroke risk factors, each SD in leukocyte count (1.8 x 10(9) cells/L) was associated with an increased risk of IS (HR 1.22, 95% CI 1.05 to 1.42), and IS, MI, or vascular death (HR 1.13, 95% CI 1.02 to 1.26). Compared with those in the lowest quartile of leukocyte count, those in the highest had an increased risk of IS (adjusted HR 1.75, 95% CI 1.08 to 2.82). The effect on atherosclerotic and cardioembolic stroke was greater than in other stroke subtypes. CONCLUSION: Relative elevations in leukocyte count are independently associated with an increased risk of future ischemic stroke and other cardiovascular events.

Association of infratentorial brain arteriovenous malformations with hemorrhage at initial presentation.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the association of hemorrhagic presentation with infratentorial brain arteriovenous malformations (AVMs). METHODS: The 623 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analyzed in a cross-sectional study. Clinical presentation (diagnostic event) was categorized as intracranial hemorrhage or nonhemorrhagic presentation. From brain imaging and cerebral angiography, AVM location was classified as either infratentorial or supratentorial. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size and location, venous drainage pattern, and associated (ie, feeding artery or intranidal) arterial aneurysms on the likelihood of hemorrhage at initial AVM presentation. RESULTS: Of the 623 patients, 72 (12%) had an infratentorial and 551 (88%) had a supratentorial AVM. Intracranial hemorrhage was the presenting symptom in 283 patients (45%), and infratentorial AVM location was significantly more frequent (18%) among patients who bled initially (6%; odds ratio [OR], 3.60; 95% confidence interval [CI], 2.09 to 6.20). This difference remained significant (OR, 1.99; 95% CI, 1.07 to 3.69) in the multivariate logistic regression model controlling for age, sex, AVM size, deep venous drainage, and associated arterial aneurysms. In the same model, the effect of other established determinants for AVM hemorrhage--ie, AVM size (in 1-mm increments; OR, 0.95; 95% CI, 0.94 to 0.96), deep venous drainage (OR, 3.09; 95% CI, 1.87 to 5.12), and associated aneurysms (OR, 2.78; 95% CI, 1.76 to 4.40)--remained significant. CONCLUSIONS: Our findings suggest that infratentorial AVM location is independently associated with hemorrhagic AVM presentation.

Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation.

BACKGROUND AND PURPOSE: The goal of this work was to determine the effect of age at initial presentation on clinical and morphological characteristics in patients with brain arteriovenous malformation (AVM). METHODS: The 542 consecutive patients from the prospective Columbia AVM database (mean+/-SD age, 34+/-15 years) were analyzed. Univariate statistical models were used to test the effect of age at initial presentation on clinical (AVM hemorrhage, seizures, headaches, neurological deficit, other/asymptomatic) and morphological (AVM size, venous drainage pattern, AVM brain location, concurrent arterial aneurysms) characteristics. RESULTS: Hemorrhage was the presenting symptom in 46% (n=247); 29% (n=155) presented with seizures, 13% (n=71) with headaches, 7% (n=36) with a neurological deficit, and 6% (n=33) without AVM-related symptoms. Increasing age correlated positively with intracranial hemorrhage (P=0.001), focal neurological deficits (P=0.007), infratentorial AVMs (P<0.001), and concurrent arterial aneurysms (P<0.001); an inverse correlation was found with seizures (P<0.001), AVM size (P=0.001), and lobar (P<0.001), deep (P=0.008), and borderzone (P=0.014) location. No age differences were found for sex, headache, asymptomatic presentation, and venous drainage pattern. CONCLUSIONS: Our data suggest a significant interaction of patient age and clinical and morphological AVM features and argue against uniform AVM characteristics across different age classes at initial presentation. In particular, AVM patients diagnosed at a higher age show a higher fraction of AVM hemorrhage and are more likely to harbor additional risk factors such as concurrent arterial aneurysms and small AVM diameter. Longitudinal population-based AVM data are necessary to confirm these findings.

The New York Islands AVM Study: design, study progress, and initial results.

BACKGROUND AND PURPOSE: Prospective population-based data on the incidence of brain arteriovenous malformation (AVM) hemorrhage are scarce. We studied lifetime detection rates of brain AVM and incident AVM hemorrhage in a defined population. METHODS: The New York islands (ie, Manhattan Island, Staten Island, and Long Island) comprise a 9,429,541 population according to the 2000 census. Since March 15, 2000, all major New York islands hospitals have prospectively reported data on consecutive patients living in the study area with a diagnosis of brain AVM and whether the patient had suffered AVM hemorrhage. Patients living outside the ZIP code-defined study area were excluded from the study population. RESULTS: As of June 14, 2002, 284 prospective AVM patients (mean+/-SD age, 35+/-18 years; 49% women) were encountered during 21,216,467 person-years of observation, leading to an average annual AVM detection rate of 1.34 per 100,000 person-years (95% CI, 1.18 to 1.49). The incidence of first-ever AVM hemorrhage (n=108; mean age, 31+/-19 years; 45% women) was 0.51 per 100,000 person-years (95% CI, 0.41 to 0.61). The estimated prevalence of AVM hemorrhage among detected cases (n=144; mean age, 33+/-19 years; 50% women) was 0.68 per 100,000 (95% CI, 0.57 to 0.79). CONCLUSIONS: Our prospective data, spanning 27 months, suggest stable rates for AVM detection and incident AVM hemorrhage. Approximately half of AVM patients may suffer intracranial hemorrhage.

Concurrent arterial aneurysms in brain arteriovenous malformations with haemorrhagic presentation.

OBJECTIVE: To assess the effect of concurrent arterial aneurysms on the risk of incident haemorrhage from brain arteriovenous malformations (AVMs). METHODS: In a cross sectional study, 463 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analysed. Concurrent arterial aneurysms on brain angiography were classified as feeding artery aneurysms, intranidal aneurysms, and aneurysms unrelated to blood flow to the AVM. Clinical presentation (diagnostic event) was categorised as intracranial haemorrhage proved by imaging or non-haemorrhagic presentation. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size, venous drainage pattern, and the three types of aneurysms on the risk of AVM haemorrhage at initial presentation. RESULTS: Arterial aneurysms were found in 117 (25%) patients with AVM (54 had feeding artery aneurysms, 21 had intranidal aneurysms, 18 had unrelated aneurysms, and 24 had more than one aneurysm type). Intracranial haemorrhage was the presenting symptom in 204 (44%) patients with AVM. In the univariate model, the relative risk for haemorrhagic AVM presentation was 2.28 (95% confidence interval (CI) 1.12 to 4.64) for patients with intranidal aneurysms and 1.88 (95% CI 1.14 to 3.08) for those with feeding artery aneurysms. In the multivariate model an independent effect of feeding artery aneurysms (odds ratio 2.11, 95% CI 1.18 to 3.78) on haemorrhagic AVM presentation was found. No significant effect was seen for intranidal and unrelated aneurysms. The attributable risk of feeding artery aneurysms for incident haemorrhage in patients with AVM was 6% (95% CI 1% to 11%). CONCLUSIONS: The findings suggest that feeding artery aneurysms are an independent determinant for increased risk of incident AVM haemorrhage.

Risk of endovascular treatment of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce. METHODS: From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving > or =1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Rankin Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location). RESULTS: The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits (Rankin score >2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications. CONCLUSIONS: From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery.

Dysplastic vessels after surgery for brain arteriovenous malformations.

BACKGROUND AND PURPOSE: The cause and clinical significance of residual dysplastic vessels after surgery for brain arteriovenous malformations (AVM) are unclear. We studied predictors and frequency of residual dysplastic vessels on cerebral angiography after AVM surgery. METHODS: The 240 prospectively enrolled surgical patients from the New York AVM Databank underwent 269 AVM-related surgical procedures. Reported postoperative brain angiographic findings were classified post hoc as showing (1) persistent dysplastic vessels, (2) a residual AVM, (3) focal hyperemia in the surgical bed, (4) other changes, or (5) a normal angiogram. Univariate and multivariate models were applied to test for an association between residual dysplastic vessels and patient age, sex, preoperative AVM size, anatomic AVM location, number of embolization procedures before surgery, and the time interval between AVM surgery and the postoperative angiogram. RESULTS: Of the 224 documented postoperative angiograms, 78 (35%) showed dysplastic vessels, 24 (11%) had evidence for a residual AVM, 16 (7%) showed focal hyperemia, 6 (2%) revealed other findings, and 100 (45%) were normal. The number of cases showing angiographic evidence for dysplastic vessels was significantly associated with increasing size of the AVM (in millimeter increments; P=0.0001); the mean diameter of AVMs in patients showing dysplastic vessels after surgery was significantly larger (41 mm, SD +/-14) than in those without residual dysplastic vessels (27 mm, SD +/-13; P<0.001). Symptomatic postoperative intracerebral hemorrhage occurred in 4 patients (1%), in 2 of whom dysplastic vessels were seen on the postoperative angiogram. CONCLUSIONS: The findings suggest that persistent dysplastic vessels may be found in approximately one third of angiograms after AVM surgery. Preoperative AVM size was found to be an independent predictor for the occurrence of dysplastic vessels on the postoperative angiogram.

Acute cardiac allograft rejection in nitric oxide synthase-2(-/-) and nitric oxide synthase-2(+/+) mice: effects of cellular chimeras on myocardial inflammation and cardiomyocyte damage and apoptosis.

BACKGROUND: The contribution of nitric oxide synthase (NOS)-2 to myocardial inflammation and cardiomyocyte necrosis and apoptosis during allograft rejection was investigated through heterotopic cardiac transplantation in mice. METHODS AND RESULTS: In the first experiments, hearts from C3H donor mice were transplanted into NOS-2(-/-) and NOS-2(+/+) C57BL/6J.129J recipients. A second series of experiments included NOS-2(-/-) donor hearts transplanted into NOS-2(-/-) recipients and wild-type NOS-2(+/+) donor hearts transplanted into wild-type NOS-2(+/+) recipients. (All donors were C57BL/6J and recipients were C57BL/6J.129J.) In the first series of experiments, no significant differences were observed in allograft survival, rejection score, total number of apoptotic nuclei (TUNEL), total number of apoptotic cardiomyocytes, or graft NOS-2 mRNA and protein. Positive NOS-2 immunostaining occurred in endothelial cells and cardiomyocytes in the allografts; the inflammatory infiltrate was NOS-2 positive only when recipients were NOS-2(+/+). In the second series of experiments, cardiac allograft survival was significantly increased in the NOS-2(-/-) mice (26+/-13 versus 17+/-8 days, P<0.05), along with significant reductions in inflammatory infiltrate, rejection score, and total number of apoptotic nuclei (23.5+/-9.5 versus 56.4+/-15.3, P<0.01) and of apoptotic cardiomyocytes (2.9+/-1.6 versus 6.9+/-2.7, P<0.05). No NOS-2 or nitrotyrosine, a marker of peroxynitrite exposure, was detected in NOS-2(-/-) allografts transplanted into NOS-2(-/-) recipients. CONCLUSIONS: The data suggest that NO derived from NOS-2 contributes to the inflammatory response and to cardiomyocyte damage and apoptosis during acute cardiac allograft rejection.

Direct coronary artery perfusion from the left ventricle.

OBJECTIVES: Trends in coronary bypass surgery require less invasive techniques and more conduits. We investigated the ability of direct coronary perfusion from the left ventricle to support regional and global cardiac function. METHODS: A conduit was established between the left ventricle and left anterior descending coronary artery (n = 6) with an interposed Starling resistor that allowed for graded regulation of backward flow. Changes of coronary flow, regional function in the territory of the left anterior descending coronary artery, and reactive hyperemia were studied. In 3 separate dogs, functional tolerance to increased heart rate was tested. In another 3 dogs, left ventricle-left anterior descending and left ventricle-left circumflex coronary artery conduits were established simultaneously (double conduit), and global function was tested. RESULTS: Without flow regulation, flow through the left ventricle-left anterior descending conduit exhibited high peaking (102 +/- 35 mL/min), midsystolic forward flow, and large pandiastolic backward flow (peaking at -47 +/- 22 mL/min). Mean coronary flow and regional function were maintained at 46.0% +/- 7.1% (35.8%-54.2%) and 45.3% +/- 29.1% (-1.8%-74.2%) of their respective normal values. When the Starling resistor was used to regulate backward flow, these values increased to 70.8% +/- 12.5% (56.8%-90.4%) and 70.2% +/- 27.8% (23.6%-107.7%), respectively. Coronary and functional reserve with a left ventricle-left anterior descending conduit were not observed. With the double conduit, global ventricular contractility indexed by end-systolic pressure-volume relation averaged 46% +/- 35% of its normal value. CONCLUSIONS: A left ventricle-coronary artery conduit supplied approximately 45% of normal blood flow and regional function, and both were improved by regulation of backward flow. Therefore, a conduit from the left ventricle to an epicardial vessel could serve as a rapidly deployable means of revascularizing totally occluded coronary vessels for which suitable natural conduits are not available.

Measurement of myocardial blood flow with PET using 1-11C-acetate.

UNLABELLED: 11C-acetate has been used extensively for the noninvasive assessment of myocardial oxygen consumption and viability with PET. The use of early uptake of acetate by the heart to measure myocardial perfusion has been proposed. This study evaluated the application of 11C-acetate for absolute measurement of myocardial blood flow using a simple compartmental model that does not require blood sampling. METHODS: Eight healthy volunteers and 13 subjects with concentric left ventricular hypertrophy were studied under resting conditions with both 11Cacetate and 15O-water. Myocardial blood flow with 11C-acetate was obtained by fitting the first 3 min of the blood and tissue tracer activity curves to a two-compartment model. Flows obtained were compared with a validated approach using 15O-water. RESULTS: In healthy volunteers, regional myocardial perfusion at rest estimated with 11C-acetate was comparable with values obtained with 15O-water (1.06 +/- 0.25 and 0.96 +/- 0.12 mL/g/min, respectively). Perfusion in subjects with left ventricular hypertrophy was also comparable if the recovery coefficient (FMM) used was corrected for ventricular mass. If a fixed FMM was used, flow was greatly overestimated. FMM could be estimated from left ventricular mass (FMM = 0.46 + 0.002 x mass, r = 0.86, P < 0.0001). CONCLUSION: The results of this study suggest that 11C-acetate can be applied to quantitatively estimate myocardial perfusion under resting conditions using a two-compartment model without the need for blood sampling, provided that an appropriate FMM is chosen. This approach should increase the usefulness of this tracer and obviate administration of a separate tracer to independently measure perfusion.

Quantification of myocardial perfusion in human subjects using 82Rb and wavelet-based noise reduction.

UNLABELLED: Quantification of myocardial perfusion with 82Rb has been difficult to achieve because of the low signal-to-noise ratio of the dynamic data curves. This study evaluated the accuracy of flow estimates after the application of a novel multidimensional wavelet-based noise-reduction protocol. METHODS: Myocardial perfusion was estimated using 82Rb and a two-compartment model from dynamic PET scans on 11 healthy volunteers at rest and after hyperemic stress with dipyridamole. Midventricular planes were divided into eight regions of interest, and a wavelet transform protocol was applied to images and time-activity curves. Flow estimates without and with the wavelet approach were compared with those obtained using H2(15)O. RESULTS: Over a wide flow range (0.45-2.75 mL/g/min), flow achieved with the wavelet approach correlated extremely closely with values obtained with H2(15)O (y = 1.03 x -0.12; n = 23 studies, r = 0.94, P < 0.001). If the wavelet noise-reduction technique was not used, the correlation was less strong (y = 1.11 x + 0.24; n = 23 studies, r = 0.79, P < 0.001). In addition, the wavelet approach reduced the regional variation from 75% to 12% and from 62% to 11% (P < 0.001 for each comparison) for resting and stress studies, respectively. CONCLUSION: The use of a wavelet protocol allows near-optimal noise reduction, markedly enhances the physiologic flow signal within the PET images, and enables accurate measurement of myocardial perfusion with 82Rb in human subjects over a wide range of flows.

Absolute quantitation of coronary steal induced by intravenous dipyridamole.

OBJECTIVE: The study was done to determine whether coronary steal (defined as an absolute decrease in perfusion from resting blood flow) is induced by intravenous (IV) dipyridamole in patients with severe coronary artery disease (CAD). BACKGROUND: Myocardial ischemia during coronary vasodilation is usually attributed to coronary steal. However, there is limited data on the absolute magnitude of coronary steal in humans. METHODS: Eighteen patients with multivessel CAD underwent dynamic positron emission tomography (PET) imaging with 13NH3 at rest and after infusion of IV dipyridamole. Eight myocardial sectors were analyzed per short axis slice and myocardial blood flow calculated with a two-compartment model in absolute terms. RESULTS: Coronary steal occurred in 8 of the 18 patients. In the 8 patients with coronary steal, myocardial blood flow decreased from 90 +/- 18 ml/100 g/min at rest to 68 +/- 27 ml/100 g/min following dipyridamole in the segments with steal, and increased from 87 +/- 19 to 138 +/- 16 ml/100 g/min following dipyridamole in the segments without steal. Significant clinical correlates of coronary steal were either ST elevation or the combination of ST depression and angina. CONCLUSIONS: Coronary vasodilation with IV dipyridamole is associated with significant reductions in blood flow to collateral-dependent myocardium consistent with coronary steal in about 45% of patients with severe CAD.

Gender differences in the risk of ischemic stroke associated with aortic atheromas.

BACKGROUND AND PURPOSE: Atherosclerotic plaque of the proximal portion of the aorta is associated with an increased risk of ischemic stroke in the elderly. Different cutoffs of plaque thickness have been used in the literature for risk stratification and have been applied to both men and women. However, the assumption that the relationship between plaque thickness and stroke risk is the same in the 2 genders has not been proven. The aim of this study was to evaluate whether the prevalence of different degrees of aortic plaque thickness differed in men and women with ischemic stroke. METHODS: We performed transesophageal echocardiography in 152 patients aged >59 years with acute ischemic stroke (76 men and 76 women) and in 152 control subjects of similar age (70 men and 82 women). Odds ratios (ORs) for ischemic stroke with 95% CIs for different plaque thickness definitions were calculated for the overall group and separately for men and women by logistic regression analysis after adjusting for age, arterial hypertension, and hypercholesterolemia. RESULTS: Aortic plaques >/=4 mm were significantly more frequent in men than in women (31.5% versus 20.3%, respectively; P:=0.025) and were associated with ischemic stroke in both men (adjusted OR 6.0, CI 2.1 to 16.8) and women (adjusted OR 3. 2, CI 1.2 to 8.8). However, plaques 3 to 3.9 mm in thickness had a significant association with stroke in women (adjusted OR 4.8, CI 1. 7 to 15.0) but not in men (adjusted OR 0.8, CI 0.2 to 3.0). Plaques <3 mm were not associated with a significantly increased stroke risk for either sex. CONCLUSIONS: Smaller aortic plaques are significantly associated with ischemic stroke in women but not in men. If the increased prevalence of smaller plaques in women is confirmed to be associated with increased risk for embolic stroke, different cutoff points may have to be adopted in men and women for risk stratification and for decisions regarding medical intervention.

Determinants of neurological outcome after surgery for brain arteriovenous malformation.

BACKGROUND AND PURPOSE: We sought to define determinants of neurological deficit after surgery for brain arteriovenous malformation (AVM). METHODS: One hundred twenty-four prospective patients (48% women, mean age 33 years) underwent microsurgical brain AVM resection. Patients were examined by 3 study neurologists immediately before surgery, postoperatively in-hospital, by in-person long-term follow-up, and with a structured telephone follow-up. They were classified according to the 5-point Spetzler-Martin grading system, with its 3 elements: size, venous drainage pattern, and location. The functional neurological status was classified with the modified Rankin scale. Multivariate logistic regression models were applied to test the effect of patient age, gender, and the 3 Spetzler-Martin elements on early and long-term postoperative neurological complications. RESULTS: Twelve patients (10%) were classified as Spetzler-Martin grade 1; 36 (29%) as grade 2; 47 (38%) as grade 3; 26 (21%) as grade 4; and 3 (2%) as grade 5. Postoperatively, in-hospital, 51 patients (41%) showed new neurological deficits (15% disabling [ie, Rankin scale score >2] and 26% nondisabling [ie, Rankin 1 or 2]). At long-term follow-up (mean follow-up time 12 months), 47 patients (38%) revealed surgery-related neurological deficits (6% disabling; 32% nondisabling). The rate of neurological complications increased by Spetzler-Martin grade. Female gender, AVM size, and deep venous drainage were significantly associated with neurological deficits at in-hospital and long-term evaluation. For patient age and AVM location, no significant association was found. CONCLUSIONS: The findings suggest that female gender, AVM size, and AVM drainage into the deep venous system may be determinants of neurological deficit after microsurgical AVM resection.

Incident hemorrhage risk of brain arteriovenous malformations located in the arterial borderzones.

BACKGROUND AND PURPOSE: We sought to assess the relative risk of hemorrhagic presentation of brain arteriovenous malformations (AVMs) located in the arterial borderzone territories. METHODS: The 464 consecutive, prospectively enrolled patients from the New York AVM Databank were analyzed. AVM borderzone location was coded positive when the malformation was supplied by branches of at least 2 of the major circle of Willis arteries (anterior, middle, and/or posterior cerebral arteries). AVMs fed by branches of only 1 major pial or any other single artery served as a comparison group. Clinical presentation (diagnostic event) was categorized as (1) intracranial hemorrhage, proven by brain imaging, or (2) seizure, focal neurological deficit, headache, or other event with no signs of AVM hemorrhage on brain imaging. RESULTS: In 48% (n=222) of the patients, AVMs were located in the arterial borderzone territories; in 52% (n=242) a non-borderzone location was found. Hemorrhage was the presenting symptom in 44% (n=205); 28% (n=132) presented with seizures, 11% (n=52) with headaches, 7% (n=34) with a neurological deficit, and 9% (n=41) with other or no AVM-related symptoms. The frequency of incident AVM hemorrhage was significantly lower in borderzone AVMs (27%, n=61) than in non-borderzone malformations (60%, n=144; P:<0.001). This difference remained significant in a multivariate model controlling for age, sex, AVM size, deep venous drainage, and presence of aneurysms (odds ratio, 0.4; 95% CI, 0.25 to 0.66). CONCLUSIONS: Our findings suggest that borderzone location is an independent determinant for a lower risk of AVM hemorrhage at initial presentation.

Elevated levels of plasma C-reactive protein are associated with decreased graft survival in cardiac transplant recipients.

BACKGROUND: Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. METHODS AND RESULTS: We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0+/-2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure (P:=0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection (P:=0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure (P:=0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. CONCLUSIONS: These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

The epidemiology of brain arteriovenous malformations.

OBJECTIVE: Common estimates of the prevalence rate for pial arteriovenous malformations (AVMs) of the brain vary widely, and their accuracy is questionable. Our objective was to critically review the original sources from which these rates were derived and to establish best estimates for both the incidence and prevalence of the disease. METHODS: We reviewed all of the relevant original literature: autopsy series, the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage and related analyses, and other population-based studies. We also modeled the confidence intervals of estimates for a process of low prevalence such as AVMs. RESULTS: Many of the prevalence estimates (500-600/100,000 population) were based on autopsy data, a source that is inherently biased. Other estimates (140/100,000 population) originated from an inappropriate analysis of data from the Cooperative Study. The most reliable information comes from a population-based study of Olmsted County, MN, but prevalence data specific to AVMs was not found in that study. CONCLUSION: The estimates for AVM prevalence that are published in the medical literature are unfounded. Because of the rarity of the disease and the existence of asymptomatic patients, establishing a true prevalence rate is not feasible. Owing to variation in the detection rate of asymptomatic AVMs, the most reliable estimate for the occurrence of the disease is the detection rate for symptomatic lesions: 0.94 per 100,000 person-years (95% confidence interval, 0.57-1.30/100,000 person-years). This figure is derived from a single population-based study, but it is supported by a reanalysis of other data sources. The prevalence of detected, active (at risk) AVM disease is unknown, but it can be inferred from incidence data to be lower than 10.3 per 100,000 population.