Stuart Hutchison

Long-term survival in patients presenting with type B acute aortic dissection: Insights from the international registry of acute aortic dissection

Background— Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. Methods and Results— We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6±6.6%, 82.8±18.9%, and 76.2±25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P<0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P<0.01). Conclusions— Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease.

Acute Intramural Hematoma of the Aorta A Mystery in Evolution

Background—The definition, prevalence, outcomes, and appropriate treatment strategies for acute intramural hematoma (IMH) continue to be debated. Methods and Results—We studied 1010 patients with acute aortic syndromes who were enrolled in the International Registry of Aortic Dissection (IRAD) to delineate the prevalence, presentation, management, and outcomes of acute IMH by comparing these patients with those with classic aortic dissection (AD). Fifty-eight (5.7%) patients had IMH, and this cohort tended to be older (68.7 versus 61.7 years; P<0.001) and more likely to have distal aortic involvement (60.3% versus 35.3%; P<0.001) compared with 952 patients with AD. Patients with IMH described more severe initial pain than did those with AD but were less likely to have ischemic leg pain, pulse deficits, or aortic valve insufficiency; moreover, they required a longer time to diagnosis and more diagnostic tests. Overall mortality of IMH was similar to that of classic AD (20.7% versus 23.9%; P=0.57), as was mortality in patients with IMH of the descending aorta (8.3% versus 13.1%; P=0.60) and the ascending aorta (39.1% versus 29.9%; P=0.34) compared with AD. IMH limited to the aortic arch was seen in 7 patients, with no deaths, despite medical therapy in only 6 of the 7 individuals. Among the 51 patients whose initial diagnostic study showed IMH only, 8 (16%) progressed to AD on a serial imaging study. Conclusions—The IRAD data demonstrate a 5.7% prevalence of IMH in patients with acute aortic syndromes. Like classic AD, IMH is a highly lethal condition when it involves the ascending aorta and surgical therapy should be considered, but this condition is less critical when limited to the arch or descending aorta. Fully 16% of patients have evidence of evolution to dissection on serial imaging.

Testosterone Induces Dilation of Canine Coronary Conductance and Resistance Arteries In Vivo

BACKGROUND Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Like estrogen, testosterone causes relaxation of isolated rabbit coronary arterial segments. We examined the vasodilator effects of testosterone in vivo in the coronary circulation and the potential mechanisms of its actions. METHODS AND RESULTS Using simultaneous intravascular two-dimensional and Doppler ultrasound, we examined the effect of intracoronary testosterone in coronary conductance and resistance arteries in 10 anesthetized dogs (5 male, 5 female). We also assessed the contribution of NO, prostaglandins, ATP-sensitive K+ channels, and classic estrogen receptors to testosterone-induced vasodilation. Testosterone induced a significant increase in cross-sectional area, average coronary peak flow velocity, and calculated volumetric coronary blood flow at the 0.1 and 1 mumol/L concentrations. This effect was independent of sex. Pretreatment with N omega-nitro-L-arginine methyl ester to block NO synthesis decreased testosterone-induced increase in cross-sectional area, average coronary peak flow velocity, and coronary blood flow. Pretreatment with glybenclamide to assess the role of ATP-sensitive K+ channels did not influence testosterone-induced dilation in epicardial arteries but did attenuate its effect in the microcirculation. Pretreatment with indomethacin or the classic estrogen-receptor antagonist ICI 182,780 did not alter testosterone-induced changes. CONCLUSIONS Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K+ channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.

Chronobiological Patterns of Acute Aortic Dissection

Background—Chronobiological rhythms have been shown to influence the occurrence of a variety of cardiovascular disorders. However, the effects of the time of the day, the day of the week, or monthly/seasonal changes on acute aortic dissection (AAD) have not been well studied. Methods and Results—Accordingly, we evaluated 957 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2000 (mean age 62±14 years, type A 61%). A &khgr;2 test for goodness of fit and partial Fourier analysis were used to evaluate nonuniformity and rhythmicity of AAD during circadian, weekly, and monthly periods. A significantly higher frequency of AAD occurred from 6:00 am to 12:00 noon compared with other time periods (12:00 noon to 6:00 pm, 6:00 pm to 12:00 midnight, and 12:00 midnight to 6:00 am;P <0.001 by &khgr;2 test). Fourier analysis showed a highly significant circadian variation (P <0.001) with a peak between 8:00 am and 9:00 am. Although no significant variation was found for the day of the week, the frequency of AAD was significantly higher during winter (P =0.008 versus other seasons by &khgr;2 test). Fourier analysis confirmed this monthly variation with a peak in January (P <0.001). Subgroup analysis identified a significant association for all subgroups with circadian rhythmicity. However, seasonal/monthly variations were observed only among patients aged <70 years, those with type B AAD, and those without hypertension or diabetes. Conclusions—Similar to other cardiovascular conditions, AAD exhibits significant circadian and seasonal/monthly variations. Our findings may have important implications for the prevention of AAD by tailoring treatment strategies to ensure maximal benefits during the vulnerable periods.

Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene

1146 Vol 349 • April 19, 1997 hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994; 24: 490–94. 3 Kosinski DJ, Grubb BP, Elliott L, Dubois D. Treatment of malignant neurogenic syncope with dual chamber cardiac pacing and fluoxetine hydrochloride. PACE 1995; 18: 1455–57. 4 Grubb BP, Kosinski D, Samoil D, Pothoulakis A, Lorton M, Kip K. Postpartum syncope. PACE 1995; 18: 1028–31. 5 McAnally LE, Threlkeld KR, Dreyling CA. Case report of a syncopal episode associated with fluoxetine. Ann Pharm 1992; 26: 1090–91.

Titration and Implementation of Neurally Adjusted Ventilatory Assist in Critically Ill Patients

BACKGROUND Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patients respiratory drive as reflected by the diaphragm electrical activity (EAdi). We examined to what extent NAVA can unload inspiratory muscles, and whether unloading is sustainable when implementing a NAVA level identified as adequate (NAVAal) during a titration procedure. METHODS Fifteen adult, critically ill patients with a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio < 300 mm Hg were studied. NAVAal was identified based on the change from a steep increase to a less steep increase in airway pressure (Paw) and tidal volume (Vt) in response to systematically increasing the NAVA level from low (NAVAlow) to high (NAVAhigh). NAVAal was implemented for 3 h. RESULTS At NAVAal, the median esophageal pressure time product (PTPes) and EAdi values were reduced by 47% of NAVAlow (quartiles, 16 to 69% of NAVAlow) and 18% of NAVAlow (quartiles, 15 to 26% of NAVAlow), respectively. At NAVAhigh, PTPes and EAdi values were reduced by 74% of NAVAlow (quartiles, 56 to 86% of NAVAlow) and 36% of NAVAlow (quartiles, 21 to 51% of NAVAlow; p < or = 0.005 for all). Parameters during 3 h on NAVAal were not different from parameters during titration at NAVAal, and were as follows: Vt, 5.9 mL/kg predicted body weight (PBW) [quartiles, 5.4 to 7.2 mL/kg PBW]; respiratory rate (RR), 29 breaths/min (quartiles, 22 to 33 breaths/min); mean inspiratory Paw, 16 cm H(2)O (quartiles, 13 to 20 cm H(2)O); PTPes, 45% of NAVAlow (quartiles, 28 to 57% of NAVAlow); and EAdi, 76% of NAVAlow (quartiles, 63 to 89% of NAVAlow). Pao(2)/Fio(2) ratio, Paco(2), and cardiac performance during NAVAal were unchanged, while Paw and Vt were lower, and RR was higher when compared to conventional ventilation before implementing NAVAal. CONCLUSIONS Systematically increasing the NAVA level reduces respiratory drive, unloads respiratory muscles, and offers a method to determine an assist level that results in sustained unloading, low Vt, and stable cardiopulmonary function when implemented for 3 h.

Association of Painless Acute Aortic Dissection With Increased Mortality

OBJECTIVE To evaluate the clinical characteristics and outcomes of patients with painless acute aortic dissection (AAD). PATIENTS AND METHODS For this study conducted from 1997 to 2001, we searched the International Registry of Acute Aortic Dissection to identify patients with painless AAD (group 1). Their clinical features and in-hospital events were compared with patients who had painful AAD (group 2). RESULTS Of the 977 patients in the database, 63 (6.4%) had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older than those in group 2 (mean +/- SD age, 66.6 +/- 13.3 vs 61.9 +/- 14.1 years; P = .01). Type A dissection (involving the ascendIng aorta or the arch) was more frequent in group 1 (74.6% vs 60.9%; P = .03). Syncope (33.9% vs 11.7%; P < .001), congestive heart failure (19.7% vs 3.9%; P < .001), and stroke (11.3% vs 4.7%; P = .03) were more frequent presenting signs in group 1. Diabetes (10.2% vs 4.0%; P = .04), aortic aneurysm (29.5% vs 13.1%; P < .001), and prior cardiovascular surgery (48.1% vs 19.7%; P < .001) were also more common in group 1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P = .05), especially due to type B dissection (limited to the descending aorta) (43.8% vs 10.4%; P < .001), and the prevalence of aortic rupture was higher among patients with type B dissection in group 1 (18.8% vs 5.9%; P = .04). CONCLUSION Patients with painless AAD had syncope, congestive heart failure, or stroke. Compared with patients who have painful AAD, patients who have painless AAD have higher mortality, especially when AAD is type B.

Sensitivity of the Aortic Dissection Detection Risk Score, a Novel Guideline-Based Tool for Identification of Acute Aortic Dissection at Initial Presentation Results From the International Registry of Acute Aortic Dissection

Background— In 2010, the American Heart Association and American College of Cardiology released guidelines for the diagnosis and management of patients with thoracic aortic disease, which identified high-risk clinical features to assist in the early detection of acute aortic dissection. The sensitivity of these risk markers has not been validated. Methods and Results— We examined patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2009. The number of patients with confirmed acute aortic dissection who presented with 1 or more of 12 proposed clinical risk markers was determined. An aortic dissection detection (ADD) risk score of 0 to 3 was calculated on the basis of the number of risk categories (high-risk predisposing conditions, high-risk pain features, high-risk examination features) in which patients met criteria. The ADD risk score was tested for sensitivity. Of 2538 patients with acute aortic dissection, 2430 (95.7%) were identified by 1 or more of 12 proposed clinical risk markers. With the use of the ADD risk score, 108 patients (4.3%) were identified as low risk (ADD score 0), 927 patients (36.5%) were intermediate risk (ADD score 1), and 1503 patients (59.2%) were high risk (ADD score 2 or 3). Among 108 patients with no clinical risk markers present (ADD score 0), 72 had chest x-rays recorded, of which 35 (48.6%) demonstrated a widened mediastinum. Conclusions— The clinical risk markers proposed in the 2010 thoracic aortic disease guidelines and their application as part of the ADD risk score comprise a highly sensitive clinical tool for the detection of acute aortic dissection.

Testosterone Worsens Endothelial Dysfunction Associated With Hypercholesterolemia and Environmental Tobacco Smoke Exposure in Male Rabbit Aorta

OBJECTIVES To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.

Clinical presentation, management, and short-term outcome of patients with type A acute dissection complicated by mesenteric malperfusion: Observations from the International Registry of Acute Aortic Dissection

BACKGROUND Few data exist on clinical/imaging characteristics, management, and outcomes of patients with type A acute dissection and mesenteric malperfusion. METHODS Patients with type A acute dissection enrolled in the International Registry for Acute Dissection (IRAD) were evaluated to assess differences in clinical features, management, and in-hospital outcomes according to the presence/absence of mesenteric malperfusion. A mortality model was used to identify predictors of in-hospital mortality in patients with mesenteric malperfusion. RESULTS Mesenteric malperfusion was detected in 68 (3.7%) of 1809 patients with type A acute dissection. Patients with mesenteric malperfusion were more likely to be older and to have coma, cerebrovascular accident, spinal cord ischemia, acute renal failure, limb ischemia, and any pulse deficit. They were less likely to undergo surgical/hybrid treatment (52.9% vs 87.9%) and more likely to receive only medical (30.9% vs 11.6%) or endovascular (16.2% vs 0.5%) management (P < .001). Overall in-hospital mortality was 63.2% and 23.8% in patients with and without mesenteric malperfusion, respectively (P < .001). In-hospital mortality of patients with mesenteric malperfusion receiving medical, endovascular, and surgical/hybrid therapy was 95.2%, 72.7%, and 41.7%, respectively (P < .001). At multivariate analysis, male gender (odds ratio [OR], 1.7; P = .002), age (OR, 1.1/y; P = .002), and renal failure (OR, 5.9; P = .020) were predictors of mortality whereas surgical/hybrid management (OR, 0.1; P = .005) was associated with better outcome. CONCLUSIONS Type A acute aortic dissection complicated by mesenteric malperfusion is a rare but ominous complication carrying a high risk of hospital mortality. Surgical/hybrid therapy, although associated with 2-fold hospital mortality, appears to be associated with better long-term outcomes in the management of type A acute aortic dissection in this setting.