Safety and Efficacy of [177Lu]-PSMA-I&T Radioligand Therapy in Octogenarians with Metastatic Castration-Resistant Prostate Cancer: Report on 80 Patients over the Age of 80 Years.

177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new treatment option for metastatic castration-resistant prostate cancer (mCRPC). Its low toxicity profile favors use in elderly patients or in patients with critical comorbidities. The purpose of this analysis was to evaluate the efficacy and safety of [177Lu]-PSMA RLT in mCRPC patients at least 80 y old. Methods: Eighty mCRPC patients at least 80 y old underwent [177Lu]-PSMA-I&T RLT and were retrospectively selected. The patients were previously treated by androgen receptor-directed therapy, received taxane-based chemotherapy, or were chemotherapy-ineligible. The best prostate-specific antigen (PSA) response was calculated, as well as clinical progression-free survival (cPFS) and overall survival (OS). Toxicity data were acquired until 6 mo after the last treatment cycle. Results: Of 80 patients, 49 (61.3%) were chemotherapy-naïve and 16 (20%) had visceral metastases. The median number of previous mCRPC treatment regimens was 2. In total, 324 cycles (median, 4 cycles; range, 1-12) with a median cumulative activity of 23.8 GBq (interquartile range, 14.8-42.2) were applied. A PSA decline of 50% was achieved in 37 (46.3%) patients. Chemotherapy-naïve patients showed higher 50% PSA response rates than chemotherapy-pretreated patients (51.0% vs. 38.7%, respectively). Overall, median cPFS and OS were 8.7 and 16.1 mo, respectively. The median cPFS and OS of chemotherapy-naïve patients were significantly longer than those of chemotherapy-pretreated patients (10.5 vs. 6.5 mo and 20.7 vs. 11.8 mo, respectively, P < 0.05). A lower hemoglobin level and higher lactate dehydrogenase level at baseline were independent predictors of shorter cPFS and OS. Treatment-emergent grade 3 toxicities were anemia in 4 patients (5%), thrombocytopenia in 3 patients (3.8%), and renal impairment in 4 patients (5%). No nonhematologic grade 3 and no grade 4 toxicities were observed. The most frequent clinical side effects were grade 1-2 xerostomia, fatigue, and inappetence. Conclusion: [177Lu]-PSMA-I&T RLT in mCRPC patients at least 80 y old is safe and effective, comparable to previously published data on non-age-selected cohorts with a low rate of high-grade toxicities. Chemotherapy-naïve patients showed a better and longer response to therapy than taxane-pretreated patients. [177Lu]-PSMA RLT seems to be a meaningful treatment option for older patients.

Anatomic characteristics and natural history of renal artery aneurysms during longitudinal imaging surveillance.

OBJECTIVE: Renal artery aneurysms (RAAs) are uncommon, and rates of growth and rupture are unknown. Limited evidence therefore exists to guide clinical management of RAAs, particularly small aneurysms that are asymptomatic. To further characterize the natural history of RAAs, we studied anatomic characteristics and changes in diameter during imaging surveillance. METHODS: Patients evaluated for native RAAs at a single institution during a 5-year period (July 2008 to July 2013) were identified and analyzed retrospectively. Patients with two or more cross-sectional imaging studies (computed tomography or magnetic resonance imaging) more than 1 month apart were included. Demographic and clinical data were collected from medical records, and anatomic data (including aneurysm diameter, calcification, and location) were obtained from electronic images. Changes in RAA diameters over time were evaluated by plots and Wilcoxon signed rank tests. RESULTS: Sixty-eight RAAs in 55 patients were analyzed. Median follow-up was 19.4 months (interquartile range, 11.2-49.0 months). Mean age at presentation was 61.8 ± 9.8 years, and 73% of patients were women. Hypertension was prevalent among 73% of patients. Multiple RAAs were present in 18% of patients, and 24% also had arterial aneurysms of other splanchnic or iliac vessels. The majority of RAAs were calcified and located at the main renal artery bifurcation. Mean initial aneurysm diameter was 16.0 ± 6.4 mm. Median annualized growth rate was 0.06 mm (interquartile range, -0.07 to 0.33 mm; P = .11). No RAA ruptures or acute symptoms occurred during surveillance, and 10.3% of RAAs were repaired electively. CONCLUSIONS: Risk of short-term RAA growth or rupture was low. These findings suggest that annual (or less frequent) imaging surveillance is safe in the majority of patients and do not support pre-emptive repair of asymptomatic, small-diameter RAAs.

Stent effects on duplex velocity estimates.

BACKGROUND: Doppler-derived velocity criteria used to define the presence and severity of in-stent restenosis after percutaneous angioplasty and endoluminal stenting have been called into question. This study uses an in vitro flow model to examine Doppler-derived velocities after placement of balloon-expandable and self-expanding endoluminal stents (BES and SES). METHODS: An in vitro vascular circuit model consisting of a pulsatile pump, tubing, and a conduit was created. The pump was programmed to replicate the Doppler spectral waveform pattern of the renal and carotid arteries. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were estimated at five distinct conduit locations. Three replicate velocity measurements were made at each location. After initial velocity estimates, a BES or an SES was deployed within the conduit. RESULTS: Mean ± standard error PSV was 95.8 ± 2.6 cm/s, 97.0 ± 2.7 cm/s, and 101.4 ± 2.7 cm/s for unstented, BES and SES, respectively. PSV estimates were increased between unstented and stented conduits when SESs were present. The increase in mean systolic velocity of 6.4% observed with SES was statistically significant (P < 0.05). EDV values did not differ significantly across conditions. Mean ± standard error EDV was 36.2 ± 1.0 cm/s, 37.3 ± 1.1 cm/s, and 37.2 ± 1.1 cm/s for unstented, BES, and SES, respectively. CONCLUSION: The presence of an SES was associated with a less than 7% change in estimated PSV. These results suggest that Doppler velocity estimates for renal and carotid arteries are not materially affected by either BES or SES.

Anesthesia-based evaluation of outcomes of lower-extremity vascular bypass procedures.

BACKGROUND: This report examines the effects of regional versus general anesthesia for infrainguinal bypass procedures performed in the treatment of critical limb ischemia (CLI). METHODS: Nonemergent infrainguinal bypass procedures for CLI (defined as rest pain or tissue loss) were identified using the 2005 to 2008 American College of Surgeons National Surgical Quality Improvement Program database using International Classification of Disease, ninth edition, and Current Procedure Terminology codes. Patients were classified according to National Surgical Quality Improvement Program data as receiving either general anesthesia or regional anesthesia. The regional anesthesia group included those specified as having regional, spinal, or epidural anesthesia. Demographic, medical, risk factor, operative, and outcomes data were abstracted for the study sample. Individual outcomes were evaluated according to the following morbidity categories: wound, pulmonary, venous thromboembolic, genitourinary, cardiovascular, and operative. Length of stay, total morbidity, and mortality were also evaluated. Associations between anesthesia types and outcomes were evaluated using linear or logistic regression. RESULTS: A total of 5,462 inpatient hospital visits involving infrainguinal bypasses for CLI were identified. Mean patient age was 69 ± 12 years; 69% were Caucasian; and 39% were female. In all, 4,768 procedures were performed using general anesthesia and 694 with regional anesthesia. Patients receiving general anesthesia were younger and significantly more likely to have a history of smoking, previous lower-extremity bypass, previous amputation, previous stroke, and a history of a bleeding diathesis including the use of warfarin. Patients receiving regional anesthesia had a higher prevalence of chronic obstructive pulmonary disease. Tibial-level bypasses were performed in 51% of procedures, whereas 49% of procedures were popliteal-level bypasses. Cases performed using general anesthesia demonstrated a higher rate of resident involvement, need for blood transfusion, and operative time. There was no difference in the rate of popliteal-level and infrapopliteal-level bypasses between groups. Infrapopliteal bypass procedures performed using general anesthesia were more likely to involve prosthetic grafts and composite vein. Mortality occurred in 157 patients (3%). The overall morbidity rate was 37%. Mean and median lengths of stay were 7.5 days (± 8.1) and 6.0 days (Q1: 4.0, Q3: 8.0), respectively. Multivariate analyses demonstrated no significant differences by anesthesia type in the incidence of morbidity, mortality, or length of stay. CONCLUSION: These results provide no evidence to support the systematic avoidance of general anesthesia for lower-extremity bypass procedures. These data suggest that anesthetic choice should be governed by local expertise and practice patterns.

Mortality in patients with premature lower extremity atherosclerosis.

OBJECTIVE: Lower extremity peripheral artery disease occurs mostly in the elderly and is associated with high mortality. Limited data are available regarding long-term mortality in patients with premature lower extremity atherosclerosis (PLEA). Our objective was to determine the all-cause mortality and its predictors in younger PLEA patients. METHODS: We studied patients with severe PLEA who were <55 years of age at diagnosis and treated at a single academic vascular center between 1998 and 2010. Data were collected prospectively at the initial evaluation for vascular care. National Death Index and hospital records were used to determine all-cause mortality. Demographic and clinical characteristics were summarized using count (%), mean (standard deviation), or median (interquartile range), and associations with aspirin use were tested using χ2 test, t-test, or Wilcoxon test. Survival times were estimated using Kaplan-Meier estimates, and associations with covariates were tested using simple and multivariable Cox proportional hazards models. RESULTS: A total of 564 patients were analyzed (46% female; 20% nonwhite; mean age 49.4 [6.4] years). Ninety-five percent of patients had ≥2 cardiovascular risk factors, 31% had coronary artery disease (CAD), and 10% had a history of cancer. During median follow-up of 5.6 years (interquartile range, 2.3-8.3 years), 108 deaths (19%) were recorded. Two-year estimated mortality (standard error) was 6% (0.01), and 5-year estimated mortality was 16% (0.02). In univariate regression analysis, patient age (P=.04), prior amputation (P<.01), history of cancer (P=.03), and established CAD (P=.04) were associated with increased risk of mortality. Aspirin use and lipid-lowering therapy at the time of first evaluation were associated with improved survival (P<.01 and P=.02, respectively). A multivariable Cox proportional hazards model identified age (hazard ratio [HR] for 5-year increase, 1.17; 95% CI, 1.01-1.36; P=.04), prior amputation (HR, 1.99; 95% CI, 1.18-3.34; P=.01), history of cancer (HR, 2.35; 95% CI, 1.36-4.07; P<.01), and CAD (HR, 1.76; 95% CI, 1.16-2.67; P<.01) as independent predictors of mortality in patients with PLEA. Importantly, history of aspirin use had a significant protective effect (HR, 0.45; 95% CI, 0.30-0.69; P<.01). The impact of lipid-lowering therapy was no longer significant in multivariable modeling. CONCLUSIONS: Patients with PLEA demonstrate high all-cause mortality. No traditional cardiovascular risk factors predicted mortality. Aspirin therapy at the time of first evaluation was a significant and independent predictor of improved survival in patients with PLEA.

Early duplex predicts restenosis after renal artery angioplasty and stenting.

OBJECTIVE: To examine the relationship between early renal duplex sonography (RDS) and restenosis after primary renal artery percutaneous angioplasty and stenting (RA-PTAS). METHODS: Consecutive patients undergoing RA-PTAS for hemodynamically significant atherosclerotic renal artery stenosis with hypertension and/or ischemic nephropathy between September 2003 and July 2010 were identified from a prospective registry. Patients had renal RDS pre-RA-PTAS, within 1 week of RA-PTAS and follow-up RDS examinations after the first postoperative week for surveillance of restenosis. Restenosis was defined as a renal artery peak systolic velocity (PSV) ≥ 180 cm/s on follow-up RDS. Associations between RDS and restenosis were examined using proportional hazards regression. RESULTS: Eighty-three patients (59% female; 12% nonwhite; mean age, 70 ± 10 years; mean pre-RA-PTAS PSV, 276 ± 107 cm/s) undergoing 91 RA-PTAS procedures comprised the sample for this study. All procedures included a completion arteriogram demonstrating no significant residual stenosis. Mean follow-up time was 14.9 ± 10.8 months. Thirty-four renal arteries (RAs) demonstrated restenosis on follow-up with a median time to restenosis of 8.7 months. There was no significant difference in the mean PSV pre-RA-PTAS in those with and without restenosis (287 ± 96 cm/s vs 269 ± 113 cm/s; P = .455), and PSV pre-RA-PTAS was not predictive of restenosis. Within 1 week of RA-PTAS, mean renal artery PSV differed significantly for renal arteries with and without restenosis (112 ± 27 cm/s vs 91 ± 34 cm/s; P = .003). Proportional hazards regression analysis demonstrated increased PSV on first post-RA-PTAS RDS was significantly and independently associated with subsequent restenosis during follow-up (hazard ratio for 30 cm/s increase, 1.81; 95% confidence interval, 1.32-2.49; P = .0003). There was no difference in pre- minus postprocedural PSV in those with and without restenosis on follow-up (175 ± 104 cm/s vs 179 ± 124 cm/s; P = .88), nor was this associated with time to restenosis. Best subsets model selection identified first postprocedural RDS as the only factor predictive of follow-up restenosis. A receiver-operating characteristic curve was examined to assess the first week PSV post-RA-PTAS most predictive of restenosis during follow-up. The ideal cut point for RA-PSV was 87 cm/s or greater. This value was associated with a sensitivity of 82.4%, specificity of 52.6%, and area under the receiver-operating characteristic curve of 69.3%. Increased first postprocedural RA-PSV was predictive of lower estimated glomerular filtration rate in the first 2 years after the procedure (-1.6 ± 0.7 mL/min/1.73 m(2) lower estimated glomerular filtration rate per 10 cm/s increase in RA-PSV; P = .010). CONCLUSIONS: Early renal artery PSV within 1 week after RA-PTAS predicted renal artery restenosis and lower postprocedure renal function. Recurrent stenosis demonstrated no association with absolute elevation in PSV prior to RA-PTAS nor with the change in PSV after RA-PTAS. These data suggest that detectable differences exist in renal artery flow parameters following RA-PTAS that are predictive of restenosis during follow-up but are not apparent on completion arteriography or detectable by intra-arterial pressure measurements. Further study is warranted.

Diastolic function predicts survival after renal revascularization.

PURPOSE: The purpose of this study was to define the relationship between left ventricular diastolic function and survival after renal revascularization. METHODS: Seventy-six adult patients (49 women, 27 men; mean age: 63 ± 13 years) with preoperative echocardiography who underwent renal revascularization for atherosclerotic disease were identified. Diastolic function was estimated from the early diastolic transmitral flow velocity (E), the atrial transmitral flow velocity (A), and the mitral annular tissue doppler velocity (e'). Patients were divided into two groups of diastolic dysfunction as either none/mild (E/A ≤ 0.75, E/e' <10) or moderate/severe (E/A >0.75, E/e' ≥ 10). Perioperative and follow-up mortality were determined from a prospective vascular database and the National Death Index. Descriptive statistics were calculated and postoperative survival was estimated by product-limit methods. Associations between preoperative factors, perioperative factors, and follow-up survival were examined using proportional hazards regression models. A forward stepwise variable selection procedure was used to select a "best" model to predict follow-up survival. RESULTS: Seventy-six patients were followed for an average of 41.9 months after renal revascularization. Within this group, 47 of 76 patients (61.8%) were identified as having moderate or severe diastolic dysfunction. Diastolic dysfunction had no apparent association with abnormal systolic function. The mean ejection fraction for those with moderate/severe diastolic dysfunction was 57.7% ± 11.5%. When comparing the moderate/severe and none/mild groupings of diastolic dysfunction, there was a significant difference in left ventricular mass index (151.9 ± 48.9 vs 125.3 ± 31.7; P = .0087). There were five deaths in the perioperative period and 20 deaths on follow-up. Among perioperative survivors, hypertension was cured or improved in 82% of the none/mild group and 53% of the moderate/severe group (P = .012). In multivariable analysis, none/mild diastolic dysfunction was significantly and independently associated with an improvement in blood pressure after revascularization (odds ratio [OR], 6.2; 95% confidence interval [CI], 1.4-28.6; P = .018). Ejection fraction was not associated with survival. After forward variable selection, moderate/severe diastolic dysfunction (hazard ratio [HR], 5.8; 95% CI 1.4-25; P = .018) was the only variable to demonstrate a significant and independent association with follow-up survival. CONCLUSION: Diastolic dysfunction, but not systolic dysfunction, was frequent in patients with renovascular disease. Blood pressure response and follow-up survival after renal revascularization demonstrated significant and independent associations with diastolic function. Consideration of diastolic function should be included in the management of patients with atherosclerotic renovascular disease.

Outcomes of acute intraoperative surgical conversion during endovascular aortic aneurysm repair.

PURPOSE: Outcomes and predictors of acute surgical conversion during endovascular aortic aneurysm repair (EVAR) were examined using the American College of Surgeons-National Safety and Quality Improvement Project (ACS-NSQIP) Database (2005 to 2008). METHODS: Acute intraoperative surgical conversions occurring during elective EVAR were identified using Current Procedural Terminology codes. Nonemergent EVAR and primary open surgical repairs of infrarenal aneurysms were examined for comparison. Perioperative morbidity was categorized as wound, pulmonary, venous thromboembolic, genitourinary, cardiovascular, operative, and septic. Mortality, overall morbidity, and length of stay (LOS) were examined. RESULTS: We identified 72 acute conversions, 2414 open repairs, and 6332 EVAR without acute conversion. Demographics and comorbidities were generally similar among operative groups. Mean operative time was 274 minutes for acute conversion vs 226 minutes for primary open repair and 162 minutes for EVAR (conversion vs EVAR and open repair vs EVAR P < .0001 for each; conversion vs open repair P = .0014; analysis on rank operative time). Blood transfusion was required in 69% of acute conversions (mean volume, 6.0 units) vs 73% of open repairs (mean volume, 3.3 units) and 12% of EVARs (mean volume, 2.6 units; P < .0001 for each pair-wise comparison; analysis on rank number of units among those transfused). Major morbidity was 28% for acute conversions, 28% for open repairs, and 12% for EVARs. Mortality was 4.2% for acute conversions, 3.2% for open repairs, and 1.3% for EVARs. Median (quartile 1, quartile 3) LOS was 7 (5, 9) days for acute conversion and open repair, and 2 (1, 3) days for EVAR. Morbidity and mortality were significantly higher for acute conversion and open repair vs EVAR. The OR (95% confidence interval) for morbidity was 2.9 (1.7-4.8) after conversion and 2.8 (2.5-3.2) after open repair (P < .0001 for both) and for mortality was 3.4 (1.0-10.9; P = .0437) for conversion and 2.5 (1.9-3.5; P < .0001) for open repair. Morbidity and mortality were similar between acute conversion and open repair. A similar pattern among repair groups was demonstrated for LOS, with similar LOS for acute conversions and open repair, which were significantly longer than those observed for EVAR. No significant demographic or medical risk factor predictors of acute conversion during EVAR were identified. CONCLUSION: Acute surgical conversion was a rare complication affecting 1.1% of EVAR cases, with no broadly identifiable at-risk population. When conversion did occur, morbidity and mortality rates paralleled those observed for elective open repair.

Results of endovascular aortic aneurysm repair with general, regional, and local/monitored anesthesia care in the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: This study examined outcomes of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using general, spinal, epidural, and local/monitored anesthesia care (MAC) in a multicenter North American hospital database reflecting contemporary anesthesia and surgical practices. METHODS: Elective EVAR cases performed between 2005 and 2008 were identified from the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes. Excluded were emergency cases and patients with concomitant procedures requiring general anesthesia. Patient-level comorbidities, characteristics, and intraoperative and postoperative details were examined. Complications were analyzed individually and in aggregate categories, including wound, pulmonary, renal, venous thromboembolic, cardiovascular, operative, and septic. Length of stay (LOS) and 30-day mortality were examined. Characteristics and outcomes were described using mean ± standard deviation or count (%), and comparisons were evaluated for statistical significance using χ(2), Fisher exact test, and univariate linear regression. LOS was analyzed with linear regression techniques using a log transformation. Associations between anesthesia type and outcomes were examined using univariable and multivariable regression techniques. RESULTS: We identified 6009 elective EVAR procedures for analysis. General anesthesia was used in 4868 cases, spinal anesthesia in 419, epidural anesthesia in 331, and local/MAC in 391. Defined morbidity occurred in 11% of patients. Median LOS was 2 (interquartile range, 1-3) days, and mean LOS was 2.8 ± 4.3 days. The 30-day mortality rate was 1.1%. Significant multivariate associations were observed between anesthesia type, pulmonary morbidity, and log-LOS. General anesthesia was associated with an increase in pulmonary morbidity vs spinal (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.3-12.5; P = .020) and local/MAC anesthesia (OR, 2.6; 95% CI, 1.0-6.4; P = .041). Use of general anesthesia was associated with a 10% increase in LOS for general vs spinal anesthesia (95% CI, 4.8%-15.5%; P = .001) and a 20% increase for general vs local/MAC anesthesia (95% CI, 14.1%-26.2%; P < .001). Trends toward increased pulmonary morbidity and LOS were not observed for general vs epidural anesthesia. No significant association between anesthesia type and mortality was observed. CONCLUSIONS: In contemporary North American anesthetic and surgical practice, general anesthesia for EVAR was associated with increased postoperative LOS and pulmonary morbidity compared with spinal and local/MAC anesthesia. These data suggest that increasing the use of less-invasive anesthetic techniques may limit postoperative complications and decrease the overall costs of EVAR.

Randomized clinical trials regarding management of atherosclerotic renovascular disease.

Prospective randomized clinical trials that support operative correction of atherosclerotic renovascular disease or catheter-based intervention compared with optimal medical management are lacking. Despite various limitations in study design, each of the five randomized trials reported to date had demonstrated no apparent benefit for renal artery intervention compared with medical management. Three ongoing randomized trials promise to provide additional data and the results of these latter studies will likely dictate future reimbursement through the Centers for Medicare and Medicaid Services.

A vascular disease educational program in the preclinical years of medical school increases student interest in vascular disease.

BACKGROUND: New training paradigms in vascular surgery necessitate medical student interest in vascular disease. We examined the effects of incorporation of a vascular disease educational program during the second year of the medical school curriculum on student acquisition of knowledge and interest in the treatment of vascular disease. METHODS: We developed and administered a new educational program on vascular disease and delivered the program to all second-year medical students. The new program encompassed 9 didactic hours, including 7 traditional lecture hours and 2 hours of problem-based learning. After completing the program, students were surveyed regarding vascular disease-specific knowledge, interest in treating vascular disease, and career choices. Third-year students who were not exposed to the program were surveyed as a control group. We recorded the voluntary student enrollment in the vascular and endovascular surgery rotation during the following academic year. Voluntary enrollment of the students exposed to the vascular disease education program was compared with enrollment for the previous 8 years. RESULTS: Before the introduction of the new educational program, 946 total lecture hours were delivered to first- and second-year medical students, comprising 490 hours (52%) given by nonsurgeon physicians, 445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93% (112 of 121) for second-year students and 95% (39 of 41) for third-year students. After the vascular disease program, second-year students answered 7.1 +/- 1.4 of 9 vascular disease questions correctly, whereas unexposed third-year students answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical students described a "somewhat" or "much greater" interest in the medical (63%), procedural (59%), and overall (63%) management of vascular disease after exposure to the program. Most also had a "somewhat" or "much greater" interest in a vascular medicine (64%) or vascular and endovascular surgery (60%) rotation. Enrollment in the vascular surgery third-year clerkship increased significantly to a mean of 3.0 students/month from 1.16 students/month in the prior year (P = .0032, postintervention year vs 8 prior years). CONCLUSION: A vascular disease educational program administered to second-year medical students increases interest in vascular disease and interest in further training. The increased interest translates to greater student enrollment in the vascular surgery clerkship in the subsequent academic year.

Accuracy of duplex sonography scans after renal artery stenting.

PURPOSE: Reports of duplex sonography scan criteria for recurrent renal arterial (RA) stenosis after endoluminal stenting have suggested that criteria for native arteries may overestimate recurrent disease. This retrospective report examines the utility of renal duplex sonography (RDS) scans to define the presence of significant (ie, ≥ 60%) renovascular disease (RVD) after percutaneous angioplasty and endoluminal stenting (PTAS). METHODS: Demographic, duplex, and angiographic data were reviewed and compared. RDS was obtained. Peak systolic velocities (PSV) were obtained after PTAS from multiple sites along the main RA from both anterior and flank approaches. Comparable images from digital subtraction angiography were independently examined for restenosis. Percent diameter stenosis was determined from the site of maximal stenosis compared with the normal RA distal to the stent. Sensitivity and specificity were estimated and 95% confidence intervals (CIs) were computed after adjusting for within patient "clustering" of observations applying native RA RDS criteria using angiography as the gold standard. Receiver operating characteristic (ROC) curves were used to estimate the optimal RDS values for recurrent stenosis. RESULTS: From October 2003 to June 2009, 49 patients had angiographic imaging after PTAS. There were 30 patients (18 women, 12 men; mean age, 71 ± 9 years) provided technically adequate paired angiographic and RDS assessment after PTAS for 66 RAs. Paired analysis was performed for 23 RAs after primary PTAS and 43 RAs after secondary treatment. The prevalence of significant restenosis was 35% (23 of 66 RAs). RAs with greater than 60% diameter restenosis had higher peak systolic velocity (PSV) compared to those without (2.48 ± 1.15 millisecond vs 1.44 ± 0.58 millisecond; P < .001). Compared to angiography, RA-PSV ≥ 1.8 millisecond with distal RA turbulence demonstrated a sensitivity of 73% (95% CI, 54%, 91%), specificity of 80% (95% CI, 67%, 93%), and an overall accuracy of 77% (95% CI, 67%, 88%) with a positive predictive value of 64% (95% CI, 46%, 82%). Optimal RDS value estimated by ROC curve resulted in RA-PSV of 2.5 millisecond which was associated with a sensitivity of 59% (95% CI, 36%, 82%), specificity of 95% (95% CI, 89%, 100%), an accuracy of 83% (95% CI, 74%, 92%), and a positive predictive value of 87% (95% CI, 68%, 100%). CONCLUSION: Renal duplex sonography has utility to detect significant restenosis after PTAS. RDS criteria for significant native RA stenosis compare favorably with optimal RDS criteria for restenosis estimated by ROC curves.

Trends in vena caval interruption.

OBJECTIVE: This study examined the national use of vena cava filters (VCFs) from 1998 to 2005. METHODS: Methods for complex surveys were used to examine hospital discharge data from the Nationwide Inpatient Sample (NIS) to determine the use of VCFs for the years 1998 to 2005. VCF placement in the absence of deep venous thrombosis (DVT) or pulmonary embolus (PE) was categorized as prophylactic. RESULTS: During the study period, the estimated rate of hospitalizations per year with a diagnosis of DVT (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.019-1.032; P < .01) or PE (OR, 1.076; 95% CI, 1.069-1.083; P < .01) rose significantly. The estimated weighted frequency of VCF placement increased from 52,860 procedures in 1998 to 104,114 procedures in 2005 (0.15% and 0.27% of all discharges, respectively), representing an 80% increase. VCF placement significantly increased during hospitalizations with any diagnosis of DVT or PE, or both, and no DVT or PE (P < .01 for each). Logistic regression models revealed that the rate of prophylactic VCF placement increased at a significantly higher rate than VCF placement associated with DVT or PE (157% vs 42%; P < .01), after adjusting for age, gender, and hospital characteristics. Prophylactic VCF placement in the setting of morbid obesity (P < .01) and head injury (P = .03) rose significantly over time. CONCLUSIONS: From 1998 to 2005, the estimated rates of prophylactic VCF placement increased at a significantly higher rate than VCF placement in the setting of DVT or PE. Significant increases in the use of prophylactic VCFs were seen in the setting of morbid obesity and head injury.

Associations between renal duplex parameters and adverse cardiovascular events in the elderly: a prospective cohort study.

BACKGROUND: Atherosclerotic renovascular disease is associated with an increased risk of cardiovascular disease (CVD) events. This study examines associations between Doppler-derived parameters from the renal artery and renal parenchyma and all-cause mortality and fatal and nonfatal CVD events in a cohort of elderly Americans. STUDY DESIGN: Cohort study. SETTING: A subset of participants from the Cardiovascular Health Study (CHS). Through an ancillary study, 870 (70% recruitment) Forsyth County, NC, CHS participants consented to undergo renal duplex sonography to define the prevalence of renovascular disease in the elderly, resulting in 726 (36% men; mean age, 77 years) technically adequate complete studies included in this investigation. PREDICTOR: Renal duplex sonography-derived Doppler signals from the main renal arteries and renal parenchyma. Spectral analysis from Doppler-shifted frequencies and angle of insonation were used to estimate renal artery peak systolic and end diastolic velocity (both in meters per second). Color Doppler was used to identify the corticomedullary junction. Using a 3-mm Doppler sample, the parenchymal peak systolic and end diastolic frequency shift (both in kilohertz) were obtained. Resistive index was calculated as (1 - [end diastolic frequency shift/peak systolic frequency shift]) using Doppler samples from the hilar arteries of the left or right kidney with the higher main renal artery peak systolic velocity. OUTCOMES & MEASUREMENTS: Proportional hazard regression analysis was used to determine associations between renal duplex sonography-derived Doppler signals and CVD events and all-cause mortality adjusted for accepted cardiovascular risk factors. Index CVD outcomes were defined as coronary events (angina, myocardial infarction, and coronary artery bypass grafting/percutaneous coronary intervention), cerebrovascular events (stroke or transient ischemic attack), and any CVD event (angina, congestive heart failure, myocardial infarction, stroke, transient ischemic attack, and coronary artery bypass grafting [CABG]/percutaneous transluminal coronary intervention [PTCI]). RESULTS: During follow-up, 221 deaths (31%), 229 CVD events (32%), 122 coronary events (17%), and 92 cerebrovascular events (13%) were observed. Renal duplex sonography-derived Doppler signals from the renal parenchyma were associated independently with all-cause mortality and CVD outcomes. In particular, increased parenchymal end diastolic frequency shift was associated significantly with any CVD event (HR, 0.73; 95% CI, 0.62-0.87; P < 0.001). Marginally significant associations were observed between increases in parenchymal end diastolic frequency shift and decreased risk of death (HR, 0.86; 95% CI, 0.73-1.00; P = 0.06) and decreased risk of cerebrovascular events (HR, 0.78; 95% CI, 0.61-1.01; P = 0.06). Parenchymal end diastolic frequency shift was not significantly predictive of coronary events (HR, 0.84; 95% CI, 0.67-1.06; P = 0.1). LIMITATIONS: CHS participants showed a "healthy cohort" effect that may underestimate the rate of CVD events in the general population. CONCLUSION: Renal duplex sonographic Doppler signals from the renal parenchyma showed significant associations with subsequent CVD events after controlling for other significant risk factors. In particular, a standard deviation increase in parenchymal end diastolic frequency shift was associated with 27% risk reduction in any CVD event.

Changes in left ventricular structure and function following renal artery revascularization.

BACKGROUND: Renovascular disease is associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction, both of which are associated with increased mortality and cardiovascular events. However, the effects of renal artery revascularization on cardiac morphology and function are poorly understood and largely based upon retrospective studies. In order to characterize changes in ventricular function and morphology following renal artery revascularization, we identified a cohort of patients with baseline preoperative echocardiograms and studied them with repeat echocardiography at 6-12 months postrevascularization. METHODS: Adult patients undergoing preoperative echocardiography and renal revascularization after March 2006 were identified from an operative registry and recruited to return for repeat echocardiography, blood pressure measurement, and collection of interval clinical and medication history 6-12 months following renal revascularization. Repeat echocardiograms were performed and interpreted according to American Society of Echocardiography recommendations for clinical trials of heart failure and other published guidelines. Systolic function was assessed as ejection fraction (EF), calculated using the modified Simpson's method. Diastolic function was categorized as normal, mild dysfunction, moderate dysfunction, or severe dysfunction based on published guidelines. Significance of longitudinal changes in continuous echocardiogram measures was assessed using paired t-tests, while longitudinal changes in categorical measures were assessed using McNemar's test. RESULTS: Twenty patients were recruited for postoperative echocardiography at a mean of 7.7 months following renal artery revascularization. Baseline systolic function was relatively preserved; mean EF was 61.3 + or - 8.5%, and only 2/20 patients (10%) had an EF <50%. Baseline diastolic dysfunction was identified in 15/20 patients (75%) and categorized as mild in one patient, moderate in 13, and severe in one. A significant mean decrease in left ventricular mass index (p = 0.018) was observed at follow-up. No significant change in EF was detected. Categorical groupwise change in diastolic dysfunction (normal/mild versus moderate/severe) was nonsignificant (p = 0.25), with two patients progressing from normal/mild to moderate/severe during follow-up and the remainder categorically unchanged. CONCLUSION: Interval decreases in left ventricular mass were observed following renal artery revascularization, while diastolic function was largely unchanged. Regression of LVH has been associated with reduced mortality and cardiovascular morbidity, and further investigation is required to understand the long-term effects of renal revascularization on survival and ventricular function. Assessment of cardiac function in the setting of symptomatic renal artery stenosis should include evaluation for diastolic dysfunction, which may represent the predominant form of target organ damage in patients with this diagnosis.

Atherosclerotic renovascular disease among hypertensive adults.

PURPOSE: This report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan. METHODS: From Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change. RESULTS: A total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 +/- 12.2 years) provided 1351 studies (mean, 3.2 +/- 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 +/- 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year +/- standard error of the mean [SEM]: 0.042 +/- 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (-0.152 +/- 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression. CONCLUSION: A total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications.

Restenosis after renal artery angioplasty and stenting: incidence and risk factors.

BACKGROUND: Management of renal artery stenosis (RAS) with primary renal artery percutaneous angioplasty and stenting (RA-PTAS) is associated with a low risk of periprocedural death and major complications; however, restenosis develops in a subset of patients and repeat intervention may be required. We examined the incidence of restenosis after RA-PTAS and associations with clinical factors. METHODS: Consecutive patients undergoing RA-PTAS for hemodynamically significant atherosclerotic RAS associated with hypertension or ischemic nephropathy, or both, between October 2003 and September 2007 were identified from a registry. Restenosis was defined using duplex ultrasound (DUS) imaging as a renal artery postintervention peak systolic velocity (PSV) >or=180 cm/s. The incidence and temporal distribution of restenosis was analyzed using survival analysis based on treated kidneys. Associations between clinical factors and recurrent stenosis were examined using proportional hazards regression. RESULTS: RA-PTAS was performed on 112 kidneys for atherosclerotic RAS during the study period. Initial postintervention renal artery DUS imaging confirming PSV <180 cm/s in 101 kidneys, which formed the basis of this analysis. Estimated restenosis-free survival was 50% at 12 months and 40% at 18 months. Decreased risk of restenosis was associated with preoperative statin use (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.16-0.74; P = .006) and increased preoperative diastolic blood pressure (DBP; HR, 0.70 per 10-mm Hg increase in preoperative DBP; 95% CI, 0.49-0.99; P = .049). No other factors assessed were associated with restenosis. CONCLUSION: Restenosis occurs in a substantial number of patients treated with RA-PTAS. Preoperative statin medication use and increased preoperative DBP are associated with reduced risk of restenosis. In the absence of contraindications, statins should be considered standard therapy for patients with atherosclerotic renal artery stenosis.

Clinical utility of the resistive index in atherosclerotic renovascular disease.

OBJECTIVE: This retrospective study examines the relationship between the renal resistive index (RI) and blood pressure and renal function response after open and percutaneous intervention for atherosclerotic renovascular disease (AS-RVD). METHODS: From March 1997 to December 2005, 86 patients (46 women, 40 men; mean age, 68 +/- 10 years) underwent renal duplex sonography (RDS), including main renal artery and hilar vessel Doppler interrogation, before treatment of AS-RVD. Of these, 56 patients had open operative repair, and 30 had percutaneous intervention. The RI (1-[EDV/PSV]) was calculated from the kidney with the highest peak systolic velocity (PSV). Hypertension response was graded from preprocedural and postprocedural blood pressure measurements and medication requirements. Renal function response was graded by a >or=20% change in estimated glomerular filtration rate (eGFR) calculated from the serum creatinine concentration. RESULTS: Comorbid conditions, baseline blood pressure, and preoperative renal function were not significantly different between open and percutaneous groups. Baseline characteristics that differed between the percutaneous vs open group were higher mean age (71 +/- 11 years vs 67 +/- 9 years; P = .05), kidney length (11.3 +/- 1.3 cm vs 10.7 +/- 1.2 cm; P = .02), proportion of patients with RI >or=0.8 (50% vs 21%; P = .01), and proportion of bilateral AS-RVD (37% vs 80%; P < .01). After controlling for preintervention blood pressure and extent of repair, postoperative eGFR differed significantly for RI <0.8 or >or=0.8 when all patients (P = .003) and percutaneous intervention (P = .008) were considered. Specifically, eGFR declined from preprocedure to postprocedure in the patients with RI >or=0.8 after percutaneous repair and in the group analyzed as a whole. Neither systolic nor diastolic pressure after intervention demonstrated an association with RI. Considering all patients and both groups, multivariable proportional hazards regression models demonstrated that RI was predictive of all-cause mortality. RI was the most powerful predictor of death during follow-up (hazard ratio, 6.7; 95% confidence interval, 2.6-17.2; P < .001). CONCLUSION: After intervention for AS-RVD, RI was associated with renal function, but not blood pressure response. A strong, independent relationship between RI and mortality was observed for all patients and both treatment groups.

Endovascular management of atherosclerotic renovascular disease: early results following primary intervention.

OBJECTIVE: This retrospective review examines periprocedural morbidity and early functional responses to primary renal artery angioplasty and stenting (RA-PTAS) for patients with atherosclerotic renovascular disease (RVD). METHODS: Consecutive patients undergoing primary RA-PTAS for hemodynamically significant atherosclerotic RVD with hypertension and/or ischemic nephropathy were identified from a prospectively maintained registry. Hypertension responses were determined based on pre- and post-intervention blood pressure measurements and medication requirements. Estimated glomerular filtration rate (eGFR) was used to determine renal function responses. Both hypertension and renal function responses were assessed at least three weeks after RA-PTAS. Stepwise multivariable regression analysis was used to examine associations between blood pressure and renal function responses to RA-PTAS and select clinical variables. RESULTS: One-hundred ten primary RA-PTAS were performed on 99 patients with atherosclerotic RVD with a mean angiographic diameter-reducing stenosis of 79.2 +/- 12.9%. All patients had hypertension (mean of 3.4 +/- 1.3 antihypertensive agents). Mean pre-intervention eGFR was 49.9 +/- 22.7 mL/min/1.73 m(2), and 74 patients had a pre-intervention eGFR < 60 mL/min/1.73 m(2). The technical success rate for RA-PTAS was 94.5%. The periprocedural complication rate was 5.5%; there were no periprocedural deaths. Statistically significant decreases in mean systolic blood pressure (161.3 +/- 25.2 vs. 148.5 +/- 25.2 post-intervention, P < .0001), diastolic blood pressure (78.6 +/- 13.3 versus 72.5 +/- 13.5 post-intervention, P < .0001), and number of antihypertensive agents (3.3 +/- 1.2 versus 3.1+/- 1.3 post-intervention, P = .009) were observed. Assessed categorically, hypertension response to RA-PTAS was cured in 1.1%, improved in 20.5%, and unchanged in 78.4%. Categorical eGFR response to RA-PTAS was improved in 27.7%, unchanged in 65.1%, and worsened in 7.2%. Multivariable stepwise regression revealed associations between pre- and post-intervention systolic blood pressure (P < .0001), diastolic blood pressure (P < .0001), and eGFR (P < .0001), as well as a trend toward improved diastolic blood pressure response among patients managed with staged bilateral intervention (P = .0589). CONCLUSION: Primary RA-PTAS for atherosclerotic RVD was associated with low peri-procedural morbidity and mortality but only modest early improvements in blood pressure and renal function. Results from ongoing prospective trials are needed to assess the long term outcomes associated with RA-PTAS and clarify its role in the management of atherosclerotic RVD.