Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3616_Библиотеки_им_академика_М_И_Перельмана

The classic Shores et al. study, although important and influential, has limitations. The study was randomized, but not blinded or placebo-controlled. There were only about 30 patients per group. Clinical endpoint analysis was based on only five patients in the treatment group and nine in the control group who reached a clinical endpoint, which failed to reach sta­tistical significance. This four-person difference between control group and treatment group seems unconvincing. The two deaths in the control group were not aortic-related on postmortem examination. Aortic diameter was not reported directly, but rather z-score (which has recently been questioned as an accurate indicator for aortic monitoring [22]). Aortic regurgi­tation was determined by auscultation. Aortic diameter was evaluated only by M-mode echocardiography. There was no computed tomography to permit assessment of aortic size above the limited echo windows. For the determination of impact on aortic growth, not the absolute diameter, but rather the ratio of the diameter to a predicted diameter (by age, weight, and height) (z-score) was used in calculations. The composite endpoint necessary to demonstrate statistical significance comprised an amalgam of factors, including aortic insufficiency and congestive failure, which are not directly morphologic aortic indicators. Additionally, the authors acknowledged that the study could not reliably monitor patient compliance with the prescribed dosage of propranolol. Although a landmark investigation, the small patient number and inherent limita­tions of the Shores study do not unequivocally establish β-blockade as beneficial in Marfan syndrome. Most importantly, because the study examined the effects of β-blockade exclusively on patients with Marfan syndrome, the results should not be extrapolated to the general population with TAA.

17 Arterial stiffness 12 (±) Pilot study suggesting that atenolol

However, there may exist room for optimism in the use of ARBs to treat TAA. A recent study investigating the effect of statins among patients with TAA (discussed in more detail later in this chapter) incidentally found that a large proportion of patients taking statin were also treated with ARB [35]. Surprised by this finding, the investigators further evaluated how ARB therapy might have confounded their findings. Both statins and ARBs were independently associated with a decreased odds of requiring surgery, and the authors proposed a potential role for combination of statin and ARB. Interestingly, the study examined the therapeutic effects of these medications at different segments of the aorta, and ARBs exerted clinical benefit in all segments of the aorta except for the aortic root. Because these data were in contrast to those obtained by Brooke et al. [27], it has been suggested that the mechanism that drives aortic root aneurysms could differ between patients with and without Marfan syndrome.

Unfortunately, and for a variety of reasons described elsewhere [53], acute aortic events—such as dissection or rup­ture—occur. As noted above, a type A aortic dissection is almost always fatal, with mortalities of 1% per hour and an expected 90-day mortality of 70%–90% [54]. The causes of death because of aortic dissection are multifactorial and include associated cardiac tamponade, aortic regurgitation, obstruction of coronary ostia leading to myocardial infarc­tion, or end-organ failure anywhere in the body because of branch vessel obstruction [55,56]. It is also important to note that acute aortic dissection is not a rare event. In fact, it is the most common acute event affecting the aorta–even more common than rupture of abdominal aneurysms because of atherosclerosis. Management recommendations are based largely on the location of the initial tear—whether the dissection originates in the ascending or descending aortic seg­ments. In general, type A dissection is a surgical emergency. Type B dissections are generally medically treated, but may require surgical intervention if specific complications occur (such as organ ischemia, rupture, or rapid expansion). Even though acute type A dissection is a surgical emergency, medical management is certainly part of the initial stabilization of these patients such as during clinical evaluation, radiographic studies, and in transport to the operating room. The overall goals of therapy are elimination of pain and a reduction of systolic blood pressure to 100–120 mmHg (mean arte­rial pressure of 60–75 mmHg) or the lowest pressure that is compatible with sufficient organ function [57]. Particularly in the acute setting, inducing low blood pressure in patients with chronic hypertension may ameliorate the damage from the dissection at the expense of impaired organ function. The reduced pressure may be insufficient for perfusion of vas­cular beds in the brain, kidneys, and coronaries.