Improved survival with statins, angiotensin receptor blockers, and steroid weaning after heart transplantation.

Various immunosuppressive and adjunctive pharmacological regimens exist for cardiac transplantation, though the associations between these regimens and long-term survival are unclear. We reviewed demographic, clinical, and pharmacological data from 220 consecutive adult heart transplant recipients between 1986 and 2003 who survived beyond 3 months. Immunosuppression was cyclosporine-based (n=94) or tacrolimus-based (n=126), and 104 patients were weaned off steroids (all receiving tacrolimus). Covariates of mortality were assessed in a Cox proportional hazards analysis. The mean age was 5.2+/-13 years. Survival was 96%, 88%, and 81% at 1, 3, and 5 years, respectively. Significant covariates associated with mortality included pretransplant diabetes mellitus (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.45 to 5.04), black race (HR 1.41, 95% CI 1.01 to 1.94), higher pretransplant creatinine clearance (HR 0.99, 95% CI 0.98 to 1.00), steroid withdrawal (HR 0.60, 95% CI 0.39 to 0.85), and exposure to a statin (HR 0.53, 95% CI 0.40 to 0.70) or an angiotensin receptor blocker (HR 0.50, 95% CI 0.20 to 0.95) after transplantation. Treatment with a statin, an angiotensin receptor blocker, and steroid withdrawal were each associated with improved survival in heart transplant recipients. These findings warrant prospective study, with specific emphasis on identifying the clinical effects of these medications in transplant recipients.

Can initial tacrolimus trough levels be predicted from clinical variables?

In eligible patients, cardiac transplantation has become the definitive treatment for end-stage heart failure. The initial posttransplantation course is marked by many potential difficulties, including renal insufficiency, hemodynamic instability, and perioperative bleeding. It is important to prevent early rejection; calcineurin inhibitors, such as tacrolimus or cyclosporine, are integral parts of such management. However, these drugs are associated with renal toxicity in some patients. Previous work suggests that limiting the increase in tacrolimus levels is associated with less renal insufficiency. The hypothesis of the current study was that a combination of clinical or laboratory variables could identify patients at risk for rapid changes in tacrolimus target levels. No single variable was strongly associated with high resultant trough levels following a standard 1-mg oral "test dose" of tacrolimus. However, the combination of 2 indices of liver metabolism (alanine aminotransferase and total bilirubin) along with serum creatinine did identify patients who tended toward elevated levels of tacrolimus (> or =4.5 ng/dL). Other variables, such as demographics, and even functional variables, such as right ventricular function by echocardiography, did not enhance the predictive value of this simple scoring system.

Changes in regional cerebral blood flow under hypothermic selective cerebral perfusion.

OBJECTIVE: Currently the most frequently used perfusion technique during aortic arch surgery to prevent cerebral damage is hypothermic selective cerebral perfusion (SCP). Changes in cerebral blood flow (CBF) are known to occur during these procedures. We investigated regional changes of CBF under conditions of SCP in a porcine model. METHODS: In this blinded study, twenty-three juvenile pigs (20 - 22 kg) were randomized after cooling to 20 degrees C on CPB. Group I (n = 12) underwent SCP for 90 minutes, while group II (n = 11) underwent total body perfusion. Fluorescent microspheres were injected at seven time-points to calculate total and regional CBF. Hemodynamics, intracranial pressure (ICP), cerebrovascular resistance (CVR) and oxygen consumption were assessed. Tissue samples from the neocortex, cerebellum, hippocampus and brain stem were taken for a microsphere count. RESULTS: CBF decreased significantly (p = 0.0001) during cooling, but remained at significantly higher levels with SCP than with CPB throughout perfusion (p < 0.0001) and recovery (p < 0.0001). These findings were similar among all regions of the brain, certainly at different levels. Neocortex CBF decreased 50%, whereas brain stem and hippocampus CBF decreased by only 25 % during total body perfusion. All four regions showed 10 - 20% less CBF in the post-CPB period. CBF during SCP did not fall by more than 20% in any analysed region. The hippocampus turned out to have the lowest CBF, while the neocortex showed the highest CBF. CONCLUSION: SCP improves CBF in all regions of the brain. Our study characterizes the brain specific hierarchy of blood flow during SCP and total body perfusion. These dynamics are highly relevant for clinical strategies of perfusion.

Refractory humoral cardiac allograft rejection successfully treated with a single dose of rituximab.

Despite improvements in immunosuppression over the last two decades, the risk of allograft rejection is still high in the early postoperative period. Cellular rejection accounts for the majority of these episodes. However, humoral rejection is a distinct phenomenon that carries a high rate of graft loss and mortality. The currently available treatments for this serious clinical problem include anti-lymphocyte antibodies, immune globulin infusions, as well as plasmapheresis, all of which have limitations. We describe a case of refractory humoral cardiac rejection successfully treated with a single dose of rituximab (375 mg/m2). No further episodes occurred with 2 years of follow-up.

Cardiac transplantation in the older recipient: excellent long-term survival based on pretransplant screening.

BACKGROUND: Cardiac transplantation has become the established treatment of choice for eligible patients with end-stage congestive heart failure. Older recipients (over the age of 60) are sometimes regarded as too high risk for transplant. Because chronological age is frequently disparate from physiologic age, we hypothesized that with careful selection after a comprehensive screening evaluation we would be able to achieve comparable survival and quality of life in an older population. METHODS: Between January 1989 and December 2002, 240 de novo adult cardiac transplants were performed for 74 female and 176 male patients. Prior to listing for cardiac transplantation, the patients were evaluated to exclude significant comorbidities that would limit survival or functional capacity postsurgery. In patients over the age of 60, particularly rigorous testing was conducted to eliminate significant extracardiac disease. RESULTS: The patients are divided in this analysis into three groups based on age at transplant (age 18 to 45, 46 to 59, and 60 years or older). Older recipients experienced similar rates of moderately severe cellular rejection (ISHLT grade 3A/ B). Survival as derived by Kaplan-Meier analysis was equivalent for all groups by Mantel-Cox logrank test (P = NS). The survival for patients older than age 60 was 83.1%, 73.7%, 67.7%, 57.4%, and 43.1% at 1,3, 5, 7, and 10 years posttransplant, respectively. CONCLUSION: We conclude that chronological age over 60 years old should not exclude a patient from the potential long-term benefit of cardiac transplant, ensuring added longevity and excellent quality of life.

Risk of spinal cord ischemia after endograft repair of thoracic aortic aneurysms.

BACKGROUND: Surgical repair of thoracoabdominal aneurysms may be associated with a significant risk of perioperative morbidity including spinal cord ischemia, which occurs at a rate of between 5% and 21%. Spinal cord ischemia after endovascular repair of thoracic aortic aneurysms (TAAs) has also been reported. This investigation reviews the occurrence of spinal cord ischemia after endovascular repair of descending TAAs at the Mount Sinai Medical Center. PATIENTS AND METHODS: Between May 1997 and April 2001, 53 patients underwent endovascular exclusion of their TAA. Preprocedure computed tomography scanning and angiography were performed on all patients. All were performed in the operating room using C-arm fluoroscopy. Physical examinations and computed tomography scans were performed at discharge and at 1, 3, 6, and 12 months postoperatively and then annually thereafter. Spinal cord ischemia developed in three of the 53 patients (5.7%) postoperatively. In one patient, cord ischemia developed that manifested as early postoperative left leg weakness occurring after concomitant open infrarenal abdominal and endovascular TAA repair. The neurologic deficit resolved 12 hours after spinal drainage, steroid bolus, and the maintenance of hemodynamic stability. The remaining two patients developed delayed onset paralysis, one patient on the second postoperative day and the other patient 1 month postrepair. Both of these patients had previous abdominal aortic aneurysm repair, and both required long grafts to exclude an extensive area of their thoracic aortas. Irreversible cord ischemia and paralysis occurred in both of these patients. CONCLUSIONS: Endovascular repair of TAA has shown a promising reduction in operative morbidity; however, the risk of spinal cord ischemia remains. Concomitant or previous abdominal aortic aneurysm repair and long segment thoracic aortic exclusion appear to be important risk factors. Spinal cord protective measures (ie, cerebrospinal fluid drainage, steroids, prevention of hypotension) should be used for patients with the aforementioned risk factors undergoing endovascular TAA repair.

Involvement of apoptosis in neurological injury after hypothermic circulatory arrest: a new target for therapeutic intervention?

BACKGROUND: This study was undertaken to evaluate the role of apoptosis in neurological injury after hypothermic circulatory arrest (HCA). METHODS: Twenty-one pigs (27 to 31 kg) underwent 90 minutes of HCA at 20 degrees C and were electively sacrificed at 6, 24, 48, and 72 hours, and at 7, 10, and 12 days after HCA, and compared with unoperated controls. In addition, 3 animals that had HCA at 10 degrees C, and 3 treated with cyclosporine A (CsA) in conjunction with HCA at 20 degrees C, were examined 72 hours after HCA. After selective perfusion and cryopreservation, all brains were examined to visualize apoptotic DNA fragmentation and chromatin condensation on the same cryosection of the hippocampus: fluorescent in situ end labeling (ISEL) was combined with staining with a nucleic acid-binding cyanine dye (YOYO). RESULTS: In addition to apoptosis, which was seen at a significantly higher level (p = 0.05) after HCA than in controls, two other characteristic degenerative morphological cell types (not seen in controls) were characterized after HCA. Cell death began 6 hours after HCA and reached its peak at 72 hours, but continued for at least 7 days. Compared with the standard protocol at 20 degrees C, HCA at 10 degrees C and CsA treatment both significantly reduced overall cell death after HCA, but not apoptosis. CONCLUSIONS: The data establish that significant neuronal apoptosis occurs as a consequence of HCA, but at 20 degrees C, other pathways of cell death, probably including necrosis, predominate. Although preliminary results suggest that the neuroprotective effects of lower temperature and of CsA are not a consequence of blockade of apoptotic pathways, inhibition of apoptosis nevertheless seems promising as a strategy to protect the brain from the subtle neurological injury that is associated with prolonged HCA at clinically relevant temperatures.

Apoptotic cell death in the hippocampus due to prolonged hypothermic circulatory arrest: comparison of cyclosporine A and cycloheximide on neuron survival.

OBJECTIVE: To determine whether cyclosporine A (CsA) or cycloheximide (CHX) can reduce neuronal apoptosis in the hippocampus in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS: Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In a blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), or 1 mg/kg CHX (n=8). After elective sacrifice 7 days postoperatively, brains were perfusion-fixed and the left hippocampus was examined for evidence of neuronal cell death. An in situ double-labeling method was used on cryosections to unequivocally identify apoptotic nuclei by the simultaneous visualization of DNA fragmentation and apoptotic chromatin condensation. Sections were also examined by immunocytochemistry for upregulation of the pro-apoptotic proteins Bax, activated caspase 3, and glyceraldehyde-3-phosphate dehydrogenase. RESULTS: Apoptotic nuclear degradation was clearly present in the CA1, CA2 and CA3 subregions of the hippocampus after HCA. However, there was also morphological evidence for an accompanying necrotic-like cell death. There was no significant difference between the number of apoptotic nuclei observed in CSA-treated animals, mean value 4.4+/-1.63 SEM or CHX-treated animals, mean value 4.0+/-1.92 SEM, and age-matched control HCA pigs, mean value 4.85+/-1.69 SEM, (P>0.10). CONCLUSIONS: The data clearly demonstrate apoptotic cell death in pigs after HCA by simultaneously demonstrating in situ end labeling (TUNEL reaction) and apoptotic chromatin condensation using a nucleic acid-binding dye. Since CsA shows promising neuroprotective effects in behavioral studies, and since the peak of HCA-induced apoptosis occurs earlier than 7 days, further studies will be required to determine whether CsA can improve neuronal survival in the first few days after HCA. CHX was not effective in reducing apoptosis in this model.

Cyclosporine A as a potential neuroprotective agent: a study of prolonged hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: To assess whether Cyclosporine A (CsA) or cycloheximide (CHX) can reduce ischemia-induced neurological damage by blocking apoptotic pathways, we assessed their effects on cerebral recovery in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS: Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In this blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), given intravenously before and subcutaneously for 7 days after HCA, or a single dose of 1 mg/kg CHX (n=8), given after weaning from cardiopulmonary bypass. Hemodynamics, intracranial pressure (ICP) and neurophysiological data (EEG, SSEP) were assessed for 3 h after HCA; early behavioral recovery was scored, and neurological/behavioral evaluation (9=normal) was carried out daily until elective sacrifice on postoperative day (POD) 7. Brains were selectively perfused and evaluated histopathologically for apoptosis. RESULTS: Basic hemodynamic data revealed no differences between CsA or CHX and control groups. ICP was significantly lower throughout rewarming (P=0.009) and reperfusion (P=0.05) in the CsA group. EEG recovery 3 h after HCA was observed in four of eight CsA animals but in only 1 of 12 controls (P=0.11) and one of eight CHX animals; cortical SSEP recovery also seemed faster in CsA animals, but failed to reach significance. Some early recovery scores were significantly better in the CsA group, and daily behavioral scores were consistently and significantly higher in the CsA-treated animals from POD1 through POD4. CONCLUSIONS: The data indicate that treatment with Cyclosporine A but not cycloheximide has a positive effect on cerebral recovery following HCA. Whether CsA results in inhibition of neuronal apoptosis, and/or inhibits release of cytokines and thereby reduces postischemic cerebral edema remains to be elucidated. The neuroprotective effect of CsA, if confirmed in further studies, would make its clinical application conceivable.

Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients.

OBJECTIVE: We sought to assess the optimal strategy for avoiding neurologic injury after aortic operations requiring hypothermic circulatory arrest. METHODS: All 717 patients who survived ascending aorta-aortic arch operations through a median sternotomy since 1986 were examined for factors influencing stroke. Temporary neurologic dysfunction was assessed in all patients who survived the operation without stroke since 1993. Multivariate analyses were carried out to determine independent risk factors for neurologic injury. RESULTS: Independent risk factors for stroke were as follows: age greater than 60 years (P <.001; odds ratio, 4.5); emergency operation (P =.02; odds ratio, 2.2); new preoperative neurologic symptoms (P =.05; odds ratio, 2.9); presence of clot or atheroma (P <.001; odds ratio, 4.4); mitral valve replacement or other concomitant procedures (P =.055; odds ratio, = 3.7); and total cerebral protection time, defined as the sum of hypothermic circulatory arrest and any retrograde or antegrade cerebral perfusion (P =.001; odds ratio, 1.02/min). In 453 patients surviving operations without stroke after 1993, independent risk factors for temporary neurologic dysfunction included age (P <.001; odds ratio, 1.06/y), dissection (P =.001; odds ratio, 2.2), need for coronary artery bypass grafting (P =.006; odds ratio, 2.1) or other procedures (P =.023; odds ratio, 3.4), and total cerebral protection time (P <.001; odds ratio, 1.02/min). When all patients with total cerebral protection times between 40 and 80 minutes were examined, the method of cerebral protection did not influence the occurrence of stroke, but antegrade cerebral perfusion resulted in a significant reduction in incidence on temporary neurologic dysfunction (P =.05; odds ratio, 0.3). CONCLUSIONS: The occurrence of stroke is principally determined by patient- and disease-related factors, but use of antegrade cerebral perfusion can significantly reduce the occurrence of temporary neurologic dysfunction.

Is aortic surgery using hypothermic circulatory arrest in octogenarians justifiable?

OBJECTIVE: This study was undertaken to analyze the risk of mortality and neurological complications after aortic surgery requiring hypothermic circulatory arrest (HCA) in octogenarians. METHODS: All patients of >80 years at the time of aortic surgery requiring HCA since 1988 were examined. Of 51 patients, 23 were male; the median age was 83. Twenty-six (51%) had proximal repair; the arch was replaced in eight (16%), and 17 (33%) had descending aorta repair. Eleven (22%) were emergencies. Multivariate analysis was carried out to determine the risk factors for in-hospital mortality and/or stroke (adverse outcome) using variables with P<0.1 after univariate analysis. RESULTS: The hospital mortality was 16%. Five patients suffered strokes (9.8%): only one survived >6 months, and three died before discharge. The overall adverse outcome was 22%, but elective operation was associated with much better results, with an adverse outcome of only 3.6% after operations via a median sternotomy. Adverse outcome was strikingly higher with more distal resections via a left thoracotomy: 47 vs. 8.8% for ascending aorta/arch resections (P=0.003). Emergency operation via a lateral thoracotomy was associated with a prohibitively high adverse outcome. Twenty-nine patients (73%) had temporary neurological dysfunction (TND). Multivariate analysis revealed emergency operation (P=0.01; odds ratio (OR), 10.6) and operations via a lateral thoracotomy (P=0.008; OR, 11) as independent preoperative predictors of adverse outcome. The overall survival was 66% at 2 years and 39% at 5 years, compared with 85 and 52% among age- and sex-matched controls. CONCLUSIONS: Aortic surgery utilizing HCA in octogenarians can be performed with an acceptable risk of mortality and stroke. From the evidence in this study, it seems that elective aneurysm repair via a median sternotomy can be undertaken for the usual indications, even in octogenarians. However, the enhanced vulnerability of the brain in the elderly is reflected by a high early mortality following stroke, and a high incidence of TND. Emergency operations increase the possibility of adverse outcome dramatically, and patients who require a lateral thoracotomy are at significantly higher risk than those operated via a median sternotomy.

Studies on the structure of the complex of the boron neutron capture therapy drug, L-p-boronophenylalanine, with fructose and related carbohydrates: chemical and 13C NMR evidence for the beta-D-fructofuranose 2,3,6-(p-phenylalanylorthoboronate) structure.

The complex of L-L-boronophenylalanine (L-p-BPA) with fructose has been used for the past 5 years in clinical trials of boron neutron capture therapy to treat both melanoma and glioblastoma multiforme. However, the structure of this complex in water buffered at physiologic pH has not been established. In the (1)H NMR spectra (D(2)O buffered at pD 7.4) of the complex of L-p-BPA with various carbohydrates, the upfield chemical shifts of the aromatic protons of L-p-BPA confirm that the boron atom is negatively charged and tetrahedral. In the (13)C NMR spectrum of the complex of L-p-BPA with U-(13)C labeled fructose, the chemical shifts and (1)J(CC) coupling constants are consistent with fructose adopting the beta-D-fructofuranose form. In addition, the (1)J(CC) coupling constants along with the binding constants measured for L-p-BPA with a series of monosaccharides and disaccharides seem to suggest that the beta-D-fructofuranose 2,3,6-(p-phenylalanylorthoboronate) structure strongly predominates, with free L-p-BPA and fructose the only other species detected.

Delayed chronic type A dissection following CABG: implications for evolving techniques of revascularization.

BACKGROUND: Postoperative dissection in some patients is related to manipulation of the aorta and accounts for 3% to 5% of deaths after cardiac surgery. METHODS: Between 1987 and 1999, 109 patients with previous cardiac operations were treated for chronic type A dissection. In 31 of the patients, the etiology was related to aortic manipulation. Twenty-one patients (17 men, 4 women; 67+/-13 years of age) had isolated coronary artery bypass grafting (CABG) as their first operation and were reviewed. The interval between operations was 52.9+/-47.3 months. RESULTS: Reoperation was elective in 11 patients, urgent in 10 patients. Median maximal aortic diameter was 6.8+/-2.1 cm; 9 patients had major aortic insufficiency. The intimal tear was at the partial occlusion clamp site in 12 patients (57.1%), at the cross-clamping site in 4 patients (19.1%), and at the proximal anastomosis in 1 patient (4.8%); 4 patients (19.1%) had multiple tears at several sites. Cystic media necrosis was present in 9.5% of the patients, severe atherosclerosis in 47.6% of the patients, and 42.9% of the patients had both. Nine patients (42.9%) underwent a modified Bentall procedure, 12 patients (57.1%) underwent a supracoronary anastomosis, and all had open distal anastomosis. There were two (9.5%) hospital deaths and three (14.3%) postoperative strokes. Freedom from cardiac or aorta-related mortality was 85.7% at a mean follow-up of 49.3 months. CONCLUSIONS: In patients who develop type A dissection of the aorta after previous CABG, the intimal tear most often is at partial occlusion clamp site. This complication is associated with morbidity and mortality. It remains to be seen whether the use of partial occlusion clamps on the pulsating and often diseased aorta during off-pump coronary artery bypass (OPCAB) will increase the risk of delayed iatrogenic dissections.

Surgical treatment of the dilated ascending aorta: when and how?

BACKGROUND: The aorta is considered pathologically dilated if the diameters of the ascending aorta and the aortic root exceed the norms for a given age and body size. A 50% increase over the normal diameter is considered aneurysmal dilatation. Such dilatation of the ascending aorta frequently leads to significant aortic valvular insufficiency, even in the presence of an otherwise normal valve. The dilated or aneurysmal ascending aorta is at risk for spontaneous rupture or dissection. The magnitude of this risk is closely related to the size of the aorta and the underlying pathology of the aortic wall. The occurrence of rupture or dissection adversely alters natural history and survival even after successful emergency surgical treatment. METHODS: In recommending elective surgery for the dilated ascending aorta, the patient's age, the relative size of the aorta, the structure and function of the aortic valve, and the pathology of the aortic wall have to be considered. The indications for replacement of the ascending aorta in patients with Marfan's syndrome, acute dissection, intramural hematoma, and endocarditis with annular destruction are supported by solid clinical information. Surgical guidelines for intervening in degenerative dilatation of the ascending aorta, however, especially when its discovery is incidental to other cardiac operations, remain mostly empiric because of lack of natural history studies. The association of a bicuspid aortic valve with ascending aortic dilatation requires special attention. RESULTS: There are a number of current techniques for surgical restoration of the functional and anatomical integrity of the aortic root. The choice of procedure is influenced by careful consideration of multiple factors, such as the patient's age and anticipated survival time; underlying aortic pathology; anatomical considerations related to the aortic valve leaflets, annulus, sinuses, and the sino-tubular ridge; the condition of the distal aorta; the likelihood of future distal operation; the risk of anticoagulation; and, of course, the surgeon's experience with the technique. Currently, elective root replacement with an appropriately chosen technique should not carry an operative risk much higher than that of routine aortic valve replacement. Composite replacement of the aortic valve and the ascending aorta, as originally described by Bentall, DeBono and Edwards (classic Bentall), or modified by Kouchoukos (button Bentall), remains the most versatile and widely applied method. Since 1989, the button modification of the Bentall procedure has been used in 250 patients at Mount Sinai Medical Center, with a hospital mortality of 4% and excellent long-term survival. In this group, age was the only predictor of operative risk (age > 60 years, mortality 7.3% [9/124] compared with age < 60, mortality 0.8% [1/126], p = 0.02). CONCLUSIONS: This modification of the Bentall procedure has set a standard for evaluating the more recently introduced methods of aortic root repair.

Cerebral metabolic suppression during hypothermic circulatory arrest in humans.

BACKGROUND: Hypothermic circulatory arrest (HCA) is used in surgery for aortic and congenital cardiac diseases. Although studies of the safety of HCA in animals have been carried out, the degree to which metabolism is suppressed in patients during hypothermia has been difficult to determine because of problems with serial measurements of cerebral blood flow in the clinical setting. METHODS: To quantify the degree of metabolic suppression achieved by hypothermia, we studied 37 adults undergoing operations employing HCA. Cerebral blood flow was estimated using an ultrasonic flow probe on the left common carotid artery, and cerebral arteriovenous oxygen content differences were calculated from jugular venous bulb and arterial oxygen saturations. Cerebral metabolic rates while cooling were then ascertained. The temperature coefficient, Q10, which is the ratio of metabolic rates at temperatures 10 degrees C apart, was determined. RESULTS: The human cerebral Q10 was found to be 2.3. The cerebral metabolic rate is still 17% of baseline at 15 degrees C. If one assumes that cerebral blood flow can safely be interrupted for 5 min at 37 degrees C, and that cerebral metabolic suppression accounts for the protective effects of hypothermia, the predicted safe duration of HCA at 15 degrees C is only 29 min. CONCLUSIONS: The safe intervals calculated from measured cerebral oxygen consumption suggest that shorter intervals and lower temperatures than those currently used may be necessary to assure adequate cerebral protection during hypothermic circulatory arrest.

Natural history of descending thoracic and thoracoabdominal aneurysms.

BACKGROUND: A review of 165 patients with chronic dissecting and degenerative aneurysms of the descending thoracic and thoracoabdominal aorta initially managed nonoperatively was carried out to ascertain factors associated with a high risk of rupture. METHODS: Changes in the aneurysms were followed with three-dimensional reconstructions of computed tomograph scans. Risk factors were compared in patients with dissecting and nondissecting aneurysms who experienced rupture, in whom operation was recommended during the course of follow-up, and in those without rupture or operation. RESULTS: Nondimensional variables associated with an enhanced risk of rupture include age, the presence of chronic obstructive pulmonary disease, and even uncharacteristic continued pain. Patients with rupture of dissections had significantly higher blood pressures than survivors, and significantly smaller maximal descending thoracic aortic diameters (median 5.4 cm) than patients with rupture of degenerative aneurysms (median 5.8 cm). The extent of the aneurysm, as reflected by the maximal abdominal aortic diameter, was a significant risk factor for rupture only in nondissecting aneurysms. Mortality from rupture was significantly higher in patients with chronic dissections than in patients with nondissecting aneurysms: 9/10 vs 26/34 (p = 0.004). CONCLUSIONS: Almost 20% of patients followed nonoperatively succumbed to rupture, suggesting that a more aggressive surgical approach toward patients with chronic aneurysms of the descending thoracic and thoracoabdominal aorta is warranted. An individualized risk of rupture within 1 year can now be calculated, and patients whose operative risk is lower than their calculated risk should be offered elective surgery.