Gary S. Kopf

Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size

BACKGROUND Prior work has clarified the cumulative, lifetime risk of rupture or dissection based on the size of thoracic aneurysms. Ability to estimate simply the yearly rate of rupture or dissection would greatly enhance clinical decision making for specific patients. Calculation of such a rate requires robust data. METHODS Data on 721 patients (446 male, 275 female; median age, 65.8 years; range, 8 to 95 years) with thoracic aortic disease was prospectively entered into a computerized database over 9 years. Three thousand one hundred fifteen imaging studies were available on these patients. Five hundred seventy met inclusion criteria in terms of length of follow-up and form the basis for the survival analysis. Three hundred four patients were dissection-free at presentation; their natural history was followed for rupture, dissection, and death. Patients were excluded from analysis once operation occurred. RESULTS Five-year survival in patients not operated on was 54% at 5 years. Ninety-two hard end points were realized in serial follow-up, including 55 deaths, 13 ruptures, and 24 dissections. Aortic size was a very strong predictor of rupture, dissection, and mortality. For aneurysms greater than 6 cm in diameter, rupture occurred at 3.7% per year, rupture or dissection at 6.9% per year, death at 11.8%, and death, rupture, or dissection at 15.6% per year. At size greater than 6.0 cm, the odds ratio for rupture was increased 27-fold (p = 0.0023). The aorta grew at a mean of 0.10 cm per year. Elective, preemptive surgical repair restored life expectancy to normal. CONCLUSIONS This study indicates that (1) thoracic aneurysm is a lethal disease; (2) aneurysm size has a profound impact on rupture, dissection, and death; (3) for counseling purposes, the patient with an aneurysm exceeding 6 cm can expect a yearly rate of rupture or dissection of at least 6.9% and a death rate of 11.8%; and (4) elective surgical repair restores survival to near normal. This analysis strongly supports careful radiologic follow-up and elective, preemptive surgical intervention for the otherwise lethal condition of large thoracic aortic aneurysm.

What is the appropriate size criterion for resection of thoracic aortic aneurysms

Although many articles have described techniques for resection of thoracic aortic aneurysms, limited information on the natural history of this disorder is available to aid in defining criteria for surgical intervention. Data on 230 patients with thoracic aortic aneurysms treated at Yale University School of Medicine from 1985 to 1996 were analyzed. This computerized database included 714 imaging studies (magnetic resonance imaging, computed tomography, echocardiography). Mean size of the thoracic aorta in these patients at initial presentation was 5.2 cm (range 3.5 to 10 cm). The mean growth rate was 0.12 cm/yr. Overall survivals at 1 and 5 years were 85% and 64%, respectively. Patients having aortic dissection had lower survival (83% 1 year; 46% 5 year) than the cohort without dissection (89% 1 year; 71% 5 year). One hundred thirty-six patients underwent surgery for their thoracic aortic aneurysms. For elective operations, the mortality was 9.0%; for emergency operations, 21.7%. Median size at time of rupture or dissection was 6.0 cm for ascending aneurysms and 7.2 cm for descending aneurysms. The incidence of dissection or rupture increased with aneurysm size. Multivariable regression analysis to isolate risk factors for acute dissection or rupture revealed that size larger than 6.0 cm increased the probability by 32.1 percentage points for ascending aneurysms (p = 0.005). For descending aneurysms, this probability increased by 43.0 percentage points at a size greater than 7.0 cm (p = 0.006). If the median size at the time of dissection or rupture were used as the intervention criterion, half of the patients would suffer a devastating complication before the operation. Accordingly, a criterion lower than the median is appropriate. We recommend 5.5 cm as an acceptable size for elective resection of ascending aortic aneurysms, because resection can be performed with relatively low mortality. For aneurysms of the descending aorta, in which perioperative complications are greater and the median size at the time of complications is larger, we recommend intervention at 6.5 cm.

Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody C5 Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass

BACKGROUND Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB. METHODS AND RESULTS A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (P<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase-MB release, P=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0. 05) in patients who received 1 or 2 mg/kg. CONCLUSIONS A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.

Penetrating ulcer of the thoracic aorta: What is it? How do we recognize it? How do we manage it?

BACKGROUND Although classic type A and B aortic dissections have been well described, less is known about the natural history of penetrating atherosclerotic ulcers of the thoracic aorta. This study differentiates penetrating ulcer from aortic dissection, determines the clinical features and natural history of these ulcers, and establishes appropriate correlates regarding optimal treatment. METHODS A retrospective review of patient records and imaging studies was conducted with 198 patients with initial diagnoses of aortic dissection (86 type A, 112 type B) at our institution from 1985 to 1997. RESULTS Of the 198 patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of computed tomographic scans, magnetic resonance images, angiograms, echocardiograms, intraoperative findings, or pathology reports. Two ulcers (13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the descending aorta. In comparison with those with type A or B aortic dissection, patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk for aortic rupture was higher among patients with penetrating ulcers (40.0%) than patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001). CONCLUSIONS Accurate recognition and differentiation of penetrating ulcers from classic aortic dissection at initial presentation is critical for optimal treatment of these patients. For penetrating ulcer, the prognosis may be more serious than with classic type A or B aortic dissection. Surgical management is advocated for penetrating ulcers in the ascending aorta and for penetrating ulcers in the descending aorta that exhibit early clinical or radiologic signs of deterioration.

Thromboembolic Complications After Fontan Operations

BACKGROUND Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed. METHODS AND RESULTS We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1 +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery. CONCLUSIONS Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.

Long-term experience with descending aortic dissection: The complication-specific approach

We analyzed long-term results in 71 patients (45 men and 26 women) treated over 17 years for documented descending aortic dissection. Forty-nine patients were treated medically and 22, surgically. Actuarial survival was 65% at 1 year, 57% at 3 years, 50% at 5 years, and 28% at 10 years for the whole group. For the group treated medically, survival was 73%, 63%, 58%, and 25% at 1 year, 3 years, 5 years, and 10 years, respectively, and for the group treated surgically, 47%, 40%, and 28% at 1 year, 3 years, and 5 years, respectively. Ten (20.4%) of the 49 medically treated patients died early (5 of rupture), and 14 (28.6%) died late (8 of dissection). Five medically treated patients crossed over to surgical management for complications of dissection. Among the surgically treated patients, 6 underwent standard graft replacement of the proximal descending aorta, 8 underwent the fenestration procedure (with a standardized retroperitoneal abdominal approach), and 4 underwent the thromboexclusion operation. Specific analysis of fenestration in 14 patients (including some with persistent descending aortic dissection after replacement of the ascending aorta for dissection) found it to be safe and effective. Actuarial survival after fenestration was 77%, 77%, and 53% at 1 year, 3 years, and 5 years, respectively. Thromboexclusion was found effective, and postoperative studies confirmed thrombosis of the descending aorta with preservation of the lowest intercostal arteries. Fifteen of the 21 surviving medically treated patients agreed to return for follow-up imaging. Nine had thrombosis of the false lumen. An interesting radiographic finding was that 4 of the 15 restudied patients had a saccular aneurysm in the aorta at the level of the left subclavian artery. We recommend a complication-specific approach to the management of descending aortic dissection. Uncomplicated dissection is treated medically, whereas complicated dissection is treated surgically, with realized rupture treated by standard graft replacement, limb ischemia treated by fenestration, and enlargement or impending rupture treated by thromboexclusion.

Surgical intervention criteria for thoracic aortic aneurysms : A study of growth rates and complications

BACKGROUND Evidence regarding the behavior of thoracic aortic aneurysm (TAA) is limited. This study reviews our ongoing efforts to understand the factors influencing aortic growth rates and the complications of rupture and dissection in order to define scientifically sound criteria for surgical intervention. METHODS Data from 370 patients with TAA treated at Yale University School of Medicine from January 1985 to June 1997 were analyzed. This computerized data base included 1063 imaging studies (magnetic resonance imaging, computed tomography, and echocardiography). RESULTS The mean size of the thoracic aorta in these patients at initial presentation was 5.2 cm (range 3.5-10). The mean growth rate was 0.10 cm/year. Median size at the time of rupture or dissection was 5.9 cm for ascending and 7.2 cm for descending aneurysms. The incidence of dissection or rupture increased with aneurysm size. Multivariable regression analysis to isolate risk factors for acute dissection or rupture revealed that size > or = 6.0 cm increased the probability of these devastating complications by 25.2% for ascending aneurysms (p = 0.006 compared with aneurysms 4.0-4.9 cm). For descending aneurysms > or = 7.0 cm, risk of dissection or rupture was increased by 37.3% (p = 0.031). CONCLUSIONS If the median size at time of dissection or rupture had been used as the indication for intervention, half the patients would have suffered a devastating complication before surgery. Accordingly, a criterion lower than the median is appropriate. We recommend 5.5 cm as an acceptable size for elective resection of ascending aortic aneurysms because this operation can be performed with relatively low mortality. For aneurysms of the descending aorta, where perioperative complications are greater and the median size at the time of complication is larger, we recommend intervention at 6.5 cm.

Revascularization alone (without mitral valve repair) suffices in patients with advanced ischemic cardiomyopathy and mild-to-moderate mitral regurgitation.

BACKGROUND Whether or not to perform adjunctive mitral repair in patients undergoing coronary artery bypass grafting (CABG) for advanced ischemic cardiomyopathy with moderately severe mitral regurgitation (MR) remains controversial. METHODS We examine the clinical and echocardiographic outcome after isolated CABG in 49 patients with ischemic cardiomyopathy and 1+ to 3+ MR undergoing surgical revascularization. The patients were identified for analysis of mitral valve-related issues from a larger series of 183 patients with ischemic cardiomyopathy (MUGA ejection fraction < or = 30%) undergoing CABG by a single surgeon from 1986 to 1996. Patient age was 66.3 years (mean, range 45 to 83 years). There were 5 women (10.2%) and 44 men (89.8%). Mean ejection fraction was 22.4% with a range of 10% to 30%. Thirty-four patients had preoperative congestive heart failure (70%) and 12 (25%) had pulmonary edema. Number of grafts was 2.8 (mean, range 1 to 5). The MR was 1+ in 18 patients (37.5%), 2+ in 26 (52%) and 3+ in 5 patients (10.5%). RESULTS Hospital mortality was 2.0% (1 of 49 patients). Ejection fraction improved from 22.0% to 31.5% (p < 0.05) after CABG. Mean degree of MR improved with CABG alone from 1.73 to 0.54 (p < 0.05) as measured at a mean interval of 36.9 months from CABG. New York Heart-Association congestive heart failure class improved from 3.3 to 1.8 (p < 0.05). Long-term survival was 88%, 65%, and 50% at 1, 3, and 5 years postoperatively. No patient required subsequent mitral valve operation or heart transplantation in long-term follow-up. CONCLUSIONS We conclude that, in patients with advanced ischemic cardiomyopathy and mild-to-moderate MR, isolated CABG (without mitral valve, repair) suffices, producing dramatic improvement in ejection fraction, in congestive heart failure, and in degree of MR, with excellent (relative) long-term survival. The improvement in MR likely results from improved left ventricular function and size consequent upon revascularization.

Hemodynamic evaluation before and after closure of fenestrated Fontan. An acute study of changes in oxygen delivery.

BackgroundAcute changes in hemodynamics and oxygen delivery accompanying temporary occlusion of atrial defects in 14 patients after a fenestrated Fontan procedure were evaluated at a median interval of 32 days after surgery to identify candidates for permanent transcatheter closure of their defects. Methods and ResultsPatients ranged in age from 9 months to 33 years and in weight from 7.9 to 69 kg. Right atrial (RA), left atrial (IA), and aortic pressures, mixed venous (Smvo2) and aortic (Sao2) oxygen saturation, and whole-body oxygen consumption (Vo2) were measured, and systemic blood flow (Qs), systemic oxygen transport (SOT), and oxygen extraction were calculated before and after occlusion. Smvo2, Vo2, and RA pressures did not change, but Sao2 increased from 84±6% to 95±3% (p<0.05), and IA pressures fell from 5.1±3.6 to 3.7±2.2 mm Hg (p<0.05). Qs fell from 2.4±0.7 to 1.8±0.411 · min−1 · m−2 (p<0.05), SOT fell from 425±154 to 366±112 ml · O2 · min−1 · m−2 (p<0.05), and oxygen extraction increased from 0.40±0.12 to 0.46±0.13 (p<0.05). Only one patient did not undergo definitive closure of his defect because of a marked decrease in Qs and SOT with a significant rise in RA pressure. ConclusionsAlthough delayed closure of an atrial defect in these patients improved morbidity and mortality, the complete separation of the venous and systemic circulations was accomplished at the expense of decreased Qs and oxygen delivery despite the improved level of arterial oxygenation. The resting levels of oxygen extraction are elevated and will be associated with decreased exercise capability. The long-term benefits of closure of these fenestrations are yet to be shown.

Optimal Timing of Coronary Artery Bypass Graft Surgery After Acute Myocardial Infarction

BACKGROUND To assess optimal timing for coronary artery bypass graft surgery (CABG) after an acute myocardial infarction (AMI), all patients undergoing CABG without associated procedures at our institution from January 1, 1991, to July 30, 1992, were reviewed. Patients were divided into three groups based on time from infarct to revascularization. The control group consisted of patients operated on for angina refractory to medical management. Relative risks (incident infarction group divided by incident control group) were established for need of vasopressors, new balloon to separate from bypass, perioperative myocardial infarction, and hospital mortality. METHODS AND RESULTS One hundred sixteen patients underwent CABG within 6 weeks of infarction. In the experimental group, 58 patients underwent CABG for non-Q-wave infarction, and 58 patients underwent CABG for Q-wave infarction. In the control group, 255 patients underwent surgery for angina without infarction. Patients were analyzed by group relative to the time between infarction and CABG. Patients were analyzed between infarction and CABG and assigned to one of three groups. Group 1 patients were revascularized within 48 hours; group 2, between 3 and 5 days; and group 3, after 5 days. Significance was determined by Fishers exact or Mantel-Haenszel chi 2 test where appropriate. Multivariate analysis was performed on statistics that were significant. All patients within all groups after Q-wave or non-Q-wave myocardial infarction had a significantly higher risk of needing an intra-aortic balloon pump and vasopressors to be weaned from bypass and a greater incidence of perioperative MI compared with control patients. Surgical mortality is highest immediately after Q-wave infarctions. CONCLUSIONS Patients with non-Q-wave infarction may undergo CABG relatively safely at any time. Acceptable timing for CABG after Q-wave infarction is after 48 hours.