Michael A. Coady

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.

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.

NATURAL HISTORY, PATHOGENESIS, AND ETIOLOGY OF THORACIC AORTIC ANEURYSMS AND DISSECTIONS

The natural history of thoracic aortic aneurysms and dissections is diverse, reflecting a broad spectrum of etiologies which include increasing aortic size, hypertension, and genetic factors. The pathogenesis is related to defects or degeneration in structural integrity of the adventitia, not the media, which is required for aneurysm formation. The ascending and descending aorta appear to have separate underlying disease processor that lead to a weakened vessel wall and an increased susceptibility for dissection. Etiologic factors for aortic aneurysms and dissections are multifactorial, reflecting genetic, environmental, and physiologic influences.

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.

Weight Lifting and Aortic Dissection: More Evidence for a Connection

Background/Aims: In 2003, we reported on a small number of patients in whom acute aortic dissection appeared to be causally related to intense weight lifting. If additional cases could be identified, the phenomenon of weight lifting induced aortic dissection would be further substantiated. We now report a substantially larger number of cases in which aortic dissection is associated with intense physical exertion. Methods: Additional cases of acute aortic dissection occurring at the time of intense physical exertion were accumulated and analyzed. Cases were culled from retrospective review of a large university data base and from reports forwarded to our attention from around the country. We determined type of activity bringing on symptoms, age and sex of the patients, location of the dissection (ascending or descending aorta), aortic size, therapy, and survival. Results: We identified 31 patients in whom acute aortic dissection occurred in the context of severe physical exertion, predominantly weight lifting or similar activities. All patients except one were males. Mean age was 47.3 (range = 19–76). All except four dissections were in the ascending aorta. Only three patients (9.7%) had a family history of aortic disease. Mean aortic diameter on the initial imaging study was 4.63 cm. Twenty-six of the 31 cases were diagnosed ante-mortem and 5 post-mortem. Overall, 10 of the 31 patients (32.2%) died. Of 24 patients reaching surgical therapy, 20 (83.3%) survived. Conclusion: Weight lifting related acute aortic dissection appears to be a real phenomenon, with increasing evidence for the association of extreme exertion with this catastrophic aortic event. Moderate aortic dilatation confers vulnerability to exertion-related aortic dissection. Individuals with known aortic dilatation should be cautioned to refrain from weight lifting or strenuous exertion. Routine echocardiographic screening of individuals engaging in heavy strength training should be considered, in order to prevent this tragic loss of life.

Surgical Management of Descending Thoracic Aortic Disease: Open and Endovascular Approaches A Scientific Statement From the American Heart Association

Recent years have witnessed the emergence of novel technologies that enable less invasive endovascular treatment of descending thoracic aortic disease (TAD). This has occurred against a backdrop of improved identification of various disease processes and better results with open surgical repair. The natural history of the specific acute aortic syndromes that affect the descending thoracic aorta has also been described with more clarity and has become more commonly recognized. This is in part secondary to the widespread availability and application of advanced imaging technologies that permit precise diagnoses. As data are accumulating, these pathological processes involving the descending thoracic aorta are no longer thought of as simply variants of one another but as distinct entities with well-defined clinical behavior. As the technology for endovascular repair continues to mature and its utilization increases, there is a need for a careful assessment of the current state of medical management, traditional open therapy, and evolving endovascular treatment of distinct thoracic aortic pathologies. The purpose of this scientific statement is to present a contemporary review of the various pathological processes that affect the descending thoracic aorta: Aneurysms, dissections, intramural hematomas (IMHs), penetrating atherosclerotic ulcers (PAUs), and aortic transections. These disorders will be considered in detail, with an exploration of the natural history, available treatment options, and controversies regarding management. Current intervention criteria will be reviewed with respect to both open surgical repair and endovascular treatment. Our goal is to provide the healthcare professional with a better understanding of the pathophysiology of the various disease processes that involve the descending thoracic aorta and to review current outcomes and technical pitfalls associated with these therapies to facilitate strong, evidence-based decision making in the care of these patients. Treatment of descending TAD involves complex, exigent decision making in an era of evolving technology. Survival data for nonoperative …

Hyperplastic Cellular Remodeling of the Media in Ascending Thoracic Aortic Aneurysms

Background—Progressive medial degeneration and atrophy is thought to be a cause of ascending thoracic aortic aneurysms in the elderly. Extensive apoptosis of vascular smooth muscle cells (VSMCs) has been demonstrated in the media of abdominal aortic aneurysms. We investigated whether medial atrophy from loss of VSMCs occurs in primary ascending thoracic aortic aneurysms. Methods and Results—Morphometric analysis of 28 nonaneurysmal ascending thoracic aortas and 29 ascending thoracic aortic aneurysms was performed by directly measuring the thickness of their vascular layers and by indirectly calculating the area of their vascular compartments. The cellular and matrix composition of the media was assessed at the structural, protein, and transcript levels. Despite thinning of the media secondary to vascular dilatation, there was an overall increase in the medial area of aneurysms. VSMC density was preserved, implying cellular hyperplasia as a result of the increased medial mass. There was decreased expression of matrix proteins, despite sustained synthesis of these molecules, which was associated with evidence of increased matrix degradation. The remodeling and expansion of the media was most evident in comparisons between nonaneurysmal aortas versus smaller aneurysms and did not evolve further in larger aneurysms. Conclusions—The mechanisms for luminal enlargement in thoracic and abdominal aortic aneurysms differ significantly with regard to the survival of VSMCs and atrophy of the media but share common pathophysiology involving degeneration of the matrix. Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms may be an initial adaptive response to minimize increased wall stress resulting from vascular dilatation.

Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia

Background— Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Methods and Results— Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (P<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (P=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (P=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (P=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (P=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (P=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (P=0.002), peNOS (ser1177) (P=0.04), NFkB (P=0.004), and pAkt (thr308) (P=0.001). Conclusions— Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.

Procedures for Estimating Growth Rates in Thoracic Aortic Aneurysms

Thoracic aortic aneurysms (TAAs) are potentially lethal medical conditions often requiring surgical intervention. Reliable information on TAA growth rates and associated risk factors is important for managing this challenging patient population. Unfortunately, a number of studies have employed questionable statistical methods, leading to biased and imprecise estimates. The present study describes these statistical problems in existing studies and delineates procedures for obtaining more reliable results. Using data from the Yale Center for Thoracic Aortic Disease, the study compares TAA growth rate estimates using conventional methods versus the recommended approach of instrumental variables (IV) estimation. The IV approach is designed to mitigate problems of measurement errors inherent in existing estimates of TAA growth. The results demonstrate that IV estimation yields more robust and precise estimates of TAA growth rates and risk factors for TAA growth. For example, the conventional approach yields TAA growth rates that fluctuate substantially-from 0.12 cm/yr to 0.90 cm/yr-depending on (1) the minimum serial follow-up period for patient inclusion in the study and (2) how subjects with negative measured growth rates are handled. In contrast, growth rate estimates using the IV approach are much more robust, ranging from 0.12 to 0.13 cm/yr. The 95% confidence intervals of estimated TAA growth are much more compact using the IV approach as well. We conclude that the IV estimation procedure yields more reliable estimates of TAA growth than does the conventional approach.