Aortic Expansion After Acute Type B Aortic Dissection

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1 Aortic Expansion After Acute Type B Aortic Dissection Frederik H.W. Jonker, MD, PhD, Santi Trimarchi, MD, PhD, Vincenzo Rampoldi, MD, Himanshu J. Patel, MD, Patrick O Gara, MD, FACC, Mark D. Peterson, MD, PhD, Rossella Fattori, MD, Frans L. Moll, MD, PhD, Matthias Voehringer, MD, Reed E. Pyeritz, MD, PhD, Stuart Hutchison, MD, FACC, Daniel Montgomery, MS, Eric M. Isselbacher, MD, Christoph A. Nienaber, MD, FACC, and Kim A. Eagle, MD, FACC; on behalf of the International Registry of Acute Aortic Dissection (IRAD) Investigators Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands; Policlinico San Donato I.R.C.C.S., Milan, Italy; University of Michigan Health System, Ann Arbor, Michigan; Brigham and Women s Hospital, Boston, Massachusetts; University of Toronto, Toronto, Ontario, Canada; S. Orsola University Hospital, Bologna, Italy; University Medical Center Utrecht, Utrecht, The Netherlands; Robert-Bosch-Krankenhaus, Stuttgart, Germany; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; University of Calgary, Calgary, Alberta, Canada; Massachusetts General Hospital, Boston, Massachusetts; and University of Rostock, Rostock, Germany Background. A considerable number of patients with acute type B aortic dissection (ABAD) treated with medical management alone will exhibit aortic enlargement during follow-up, which could lead to aortic aneurysm and rupture. The purpose of this study was to investigate predictors of aortic expansion among ABAD patients enrolled in the International Registry of Acute Aortic Dissection. Methods. We analyzed 191 ABAD patients treated with medical therapy alone enrolled in the registry between 1996 and 2010, with available descending aortic diameter measurements at admission and during follow-up. The annual aortic expansion rate was calculated for all patients, and multivariate regression analysis was used to investigate factors affecting the expansion rate. Results. Aortic expansion was observed in 59% of ABAD patients; mean expansion rate was mm/y. In multivariate analysis, white race (regression coefficient [RC], 4.6; 95% confidence interval [CI], 1.4 to 7.7) and an initial aortic diameter less than 4.0 cm (RC, 6.3; 95% CI, 4.0 to 8.6) were associated with increased aortic expansion. Female sex (RC, 3.8; 95% CI, 6.1 to 1.4), intramural hematoma (RC, 3.8; 95% CI, 6.5 to 1.1), and use of calcium-channel blockers (RC, 3.8; 95% CI, 6.2 to 1.3) were associated with decreased aortic expansion. Conclusions. White race and a small initial aortic diameter were associated with increased aortic expansion during follow-up, and decreased aortic expansion was observed among women, patients with intramural hematoma, and those on calcium-channel blockers. These data raise the possibility that the use of calcium-channel blockers after ABAD may reduce the rate of aortic expansion, and therefore further investigation is warranted. (Ann Thorac Surg 2012;94:1223 9) 2012 by The Society of Thoracic Surgeons The majority of patients with acute type B aortic dissection (ABAD) are treated with medical therapy alone. Surgical or endovascular treatment is usually reserved only for patients with complications at presentation such as rupture, enlarging aneurysm, retrograde dissection, or malperfusion syndromes [1 5]. In-hospital outcomes are generally acceptable in patients with uncomplicated ABAD, with up to 90% of patients surviving discharge after receiving effective antihypertensive therapy [5 8]. However, 1 in 4 ABAD patients discharged from the hospital alive will expire within three years [9, 10]. Probably the most important sequela during follow-up after ABAD treated with medical therapy alone is aortic enlargement, which could lead to aneurysm formation and rupture [6, 9, 11, 12]. Currently it is unclear Accepted for publication May 11, Address correspondence to Dr Jonker, Department of Surgery, Maasstad Hospital Rotterdam, Bulgersteyn 1c, 3011 AB Rotterdam, The Netherlands; jonkerf@maasstadziekenhuis.nl. which patients are more likely to experience aortic enlargement after medical therapy. A better understanding of the factors that affect the aortic expansion rate after ABAD could help in selecting patients who require close radiologic follow-up, and perhaps may lead to future therapies to slow aortic expansion. This may theoretically reduce the number of patients experiencing aortic rupture, improving the long-term prognosis of ABAD. The purpose of this study is to investigate predictors of aortic expansion during follow-up among ABAD patients enrolled in the International Registry of Acute Aortic Dissection (IRAD). Patients and Methods Patient Selection The IRAD is an ongoing multinational, multicenter registry that enrolls patients with acute aortic dissection at 28 large referral centers (Appendix); the inception and 2012 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 1224 JONKER ET AL Ann Thorac Surg EXPANSION OF THE DISSECTED AORTA 2012;94: structure of IRAD has been described previously [13]. All ABAD patients treated with medical therapy alone who were enrolled in the IRAD between 1996 and October 2010 were identified. All patients who died during hospitalization were excluded from this cohort. Subsequently, only those patients with available descending aortic diameter measurements at presentation and during follow-up at 6, 12, or 24 months after the acute event were included for analysis. Patients were excluded if the follow-up aortic measurements were performed after 24 months to ensure a relatively homogeneous study cohort with comparable follow-up intervals. Patients who had undergone descending aortic intervention before the follow-up measurements were excluded as well. In this manner, 191 ABAD patients were included for final analysis. Data Collection In the IRAD, patient and procedural data are collected using forms with more than 290 variables, which are submitted to the IRAD coordinating center at the University of Michigan, and checked for face validity and analytical internal validity. The initial and follow-up descending aortic diameters are measured by computed tomography or magnetic resonance imaging. If patients underwent multiple imaging studies, the study that reflected the largest aortic diameter was selected for analysis. The maximal aortic diameter was measured at cross-sectional images perpendicular to the long axis of the descending aorta. In the IRAD, all initial aortic diameter measurements were obtained after aortic dissection had occurred. Statistical Analysis Data analysis was performed by a statistician (D.M.) with the use of SPSS statistical analysis software (SPSS Inc, Chicago, IL). Summary statistics are presented as frequencies and percentages for categorical variables and mean standard deviation for continuous variables. The annual aortic expansion rate was calculated for all patients as follows: (maximal diameter at follow-up maximal initial diameter)/length of follow-up in years. If multiple aortic measurements were performed during follow-up, the most recent follow-up aortic measurements were used for calculating the annual aortic expansion rate. Multivariate linear regression analysis was used to investigate the effects of demographics, patient history, and imaging findings on the annual aortic expansion rate. Age, sex, and variables with a probability value of less than 0.2 in univariate linear regression analysis were integrated in the multivariate linear regression model to calculate independent effects on the aortic expansion rate. A probability value of less than 0.05 was considered significant. The authors had full access to and took full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. The IRAD study has been approved by the institutional review boards of all participating centers. Results Baseline Characteristics In total, 191 ABAD patients managed with medical treatment only were included for analysis. Intramural hematoma (IMH) was observed in 37% of patients, of which 17% had an isolated IMH and 20% had combined IMH and ABAD. The mean age of patients was years; 69% were men. At discharge, 93% were prescribed -blockers, and 65% of patients received calciumchannel blockers (Table 1). Practically all patients taking calcium-channel blockers were prescribed a -blocker as well. The mean descending thoracic aortic diameter at first admission, measured after the acute event, was cm. The initial descending aortic diameter was smaller than 4.0 cm in 42% of patients (Table 2). Aortic Expansion During Follow-Up The median length of follow-up was 2.0 years (interquartile range, 1 to 2 years). Aortic expansion during follow-up was observed in 59% (n 113) of patients. Overall, the mean descending aortic diameter increased from 4.2 cm to 4.5 cm (p 0.001); the mean annual expansion rate was mm/y. The aortic expansion rate showed an approximately normal distribution, ranging from 22 mm/y to 24 mm/y (Fig 1). No aortic ruptures occurred during the interval between both diameter measurements. Predictors of Aortic Expansion in Univariate Analysis In univariate linear regression analysis, the following variables significantly affected the aortic expansion rate: female sex (regression coefficient [RC], 2.8; p 0.018), Table 1. Demographics and Patient History Variable N 191 (%) Demographics Age (y), mean SD Female sex 59 (30.9) Race White 161 (86.1) African American 4 (2.1) Asian 18 (9.6) Hispanic 4 (2.1) History Marfan s syndrome 1 (2.6) Aortic valve disease 9 (4.8) Hypertension 133 (70.0) Atherosclerosis 58 (30.5) Diabetes 9 (4.8) Prior CABG 4 (2.2) Medication at discharge -Blocker 172 (92.5) ACE inhibitor 97 (53.6) Calcium-channel blocker 119 (65.4) ACE angiotensin-converting enzyme; CABG coronary artery bypass grafting; SD standard deviation.

3 Ann Thorac Surg JONKER ET AL 2012;94: EXPANSION OF THE DISSECTED AORTA 1225 Table 2. Imaging Findings at Initial Presentation Variable N (%) Descending aortic diameter (cm), mean SD 3.5 cm 39 (20.4) cm 41 (21.5) cm 41 (21.5) cm 24 (12.6) 5.0 cm 46 (24.1) Aortic arch diameter (cm), mean SD False lumen thrombosis Patent false lumen 73 (48.0) Partial thrombosis 53 (34.9) Complete thrombosis 26 (17.1) Intramural hematoma 68 (36.8) Isolated IMH 32 (17.3) Combined IMH and ABAD 36 (19.5) ABAD acute type B aortic dissection; SD standard deviation. IMH intramural hematoma; white race (RC, 5.6; p 0.001), Asian race (RC, 5.5; p 0.003), use of calcium-channel blockers (RC, 3.4; p 0.005), presence of IMH (RC, 3.7; p 0.003), and an initial descending aortic diameter of less than 4.0 cm (RC, 3.7; p 0.001; Table 3). There was a trend toward increased expansion in case of a patent false lumen (RC, 2.4; p 0.063). As the initial aortic diameter increased, the annual aortic expansion rate decreased (Fig 2). Overall, the expansion rate for patients with an initial aortic diameter of less than 4.0 cm was 3.8 mm, as compared with 0.2 mm/y for aortas of 4.0 cm or larger (p 0.001). Patients with isolated aortic dissection exhibited an average aortic expansion of 3.1 mm/y, as compared with 0.6 mm/y for isolated IMH and 1.8 mm/y for combined IMH and ABAD (p 0.002). Of all patients with a stable or decreasing aortic diameter during follow-up, 48% had IMH. The mean annual expansion rate for patients prescribed calcium-channel blockers was 0.5 mm/y compared with 3.9 mm/y for those without (p 0.005). Multivariate Linear Regression Analysis In multivariate regression analysis, white race (RC, 4.6; 95% confidence interval [CI], 1.4 to 7.7; p 0.005) and an initial aortic diameter of less than 4.0 cm (RC, 6.3; 95% CI, 4.0 to 8.6; p 0.001) were associated with increased aortic expansion. The following variables were independently associated with decreased aortic expansion during follow-up: female sex (RC, 3.8; 95% CI, 6.1 to 1.4), IMH (RC, 3.8; 95% CI, 6.5 to 1.1), and calcium-channel blockers (RC, 3.8; 95% CI, 6.2 to 1.3; Table 4). Overall, the all-cause mortality of the cohort at 5 years was 90.8%. Among patients treated with calcium-channel blocker therapy, the all-cause mortality at 5 years was 92.7%, as compared with 85.4% for those without calciumchannel blockers (p 0.126; Fig 3). Comment Although early results of uncomplicated ABAD treated with medical management alone are encouraging, up to 60% of such patients in the IRAD exhibited aortic expansion during follow-up. The overall expansion rate was approximately 1.7 mm/y in the IRAD, similar to previous analyses, which found expansion rates of approximately 1.3 to 2.6 mm/y at the level of the descending thoracic aorta [11, 12, 14]. The annual expansion rate after ABAD varies considerably among patients, so identifying patients at risk for increased aortic expansion appears crucial. Our analysis revealed multiple patient characteristics that may influence the aortic expansion rate, including demographic, morphologic, and therapeutic factors. The expansion rate was increased among male patients as compared with female patients, which may be explained by anatomic differences between both sexes. Women are typically smaller in size than men, and female aortic measurements may be reduced as well, with smaller aortic expansion rates. Racial differences in aortic expansion were observed as well. Whites exhibited on average an increased expansion rate, whereas aortic enlargement occurred less frequently among Asian patients. In abdominal aortic aneurysm, racial disparities appear to exist as well, as the prevalence of abdominal aortic aneurysm is considerably lower in the Asian population as compared with the white population [15, 16]. In addition, morphologic characteristics of the aortic pathologic process affected the aortic enlargement during follow-up. The presence of IMH was associated with a lower expansion rate as compared with isolated aortic Fig 1. Distribution of annual aortic expansion rates. The aortic expansion rate showed an approximately normal distribution. Overall, the mean annual expansion rate was mm/y, ranging from 22 mm/y to 24 mm/y.

4 1226 JONKER ET AL Ann Thorac Surg EXPANSION OF THE DISSECTED AORTA 2012;94: Table 3. Univariate Effects on the Aortic Expansion Rate (mm/y) 95% CI Expansion Rate (mm/y) Variable RC Low High Yes No p Value Demographics Age (y) Female sex Race White African American Asian Hispanic History Aortic valve disease Hypertension Atherosclerosis Diabetes Prior CABG Medication at discharge -Blocker ACE inhibitor Calcium-channel blocker Initial aortic diameter 4.0 cm False lumen thrombosis Patent false lumen Partial thrombosis Complete thrombosis Intramural hematoma a a Intramural hematoma (IMH) included both patients with an isolated IMH and a combined acute type B aortic dissection and IMH. ACE angiotensin-converting enzyme; CABG coronary artery bypass grafting; CI confidence interval; RC regression coefficient. Fig 2. Initial descending aortic diameter and mean annual expansion rate. As the initial aortic diameter increased, the mean annual aortic expansion rate decreased. dissections. In IMH, there is typically no intimal tear, which may be beneficial for the hemodynamic forces that are normally experienced in the false lumen. In patients with classic type B dissection, a patent false lumen may increase the aortic expansion rate, as demonstrated previously [11, 14, 17]. In contrast, in a thrombosed false lumen, the aorta frequently becomes a single-lumen channel, with dissected layers that become a single layer, increasing the vessel wall strength [11]. A previous IRAD study found an increased long-term mortality rate among patients with a partially thrombosed false lumen, possibly because of occlusion of distal reentry tears of the false lumen by a partial thrombus [18]. This could theoretically result in increased pressure in the false lumen, and elevated expansion and rupture risks. We could not confirm this hypothesis in the present analysis. Possibly, only those patients with a sac type partial false lumen thrombosis, in which only distal reentry tears are excluded, are at increased risk of elevated false lumen pressure and aortic expansion, as shown previously by Sueyoshi and colleagues [17]. Further research regarding the impact of false lumen thrombosis on the prognosis of ABAD is needed [17]. Surprisingly, an aortic diameter of greater than 4.0 cm at first admission was associated with decreased aortic expansion, whereas smaller aortic dissections tended to expand faster during follow-up. Sueyoshi and colleagues [11] previously found a higher aortic expansion rate in patients with relatively smaller aortic diameters as well, although this failed to reach statistical significance in

5 Ann Thorac Surg JONKER ET AL 2012;94: EXPANSION OF THE DISSECTED AORTA 1227 Table 4. Independent Predictors of Aortic Expansion 95% CI Variable Regression Coefficient Standardized Coefficient Low High p Value Age (y) Female sex White race Initial aortic diameter 4.0 cm Patent false lumen Intramural hematoma a Blocker therapy Calcium-channel blocker therapy a Intramural hematoma (IMH) included both patients with an isolated IMH as combined acute type B aortic dissection and IMH. CI confidence interval. their analysis. In aortic aneurysm, in which the vessel wall is still intact, aortic expansion increases exponentially with increasing diameter, according to Laplace s law [19, 20]. An explanation for this diameter paradox remains unclear at this moment. The risk of developing aortic dissection generally is thought to increase as the aorta enlarges [21], although the majority of type A and B aortic dissections still occurs in aortic diameters smaller than the threshold for elective intervention (5.5 cm) [22, 23]. Patients with relatively normal aortic measurements exhibiting aortic dissection may have more severe aortic wall abnormalities, possibly caused by connective tissue disorders, as compared with those experiencing aortic Fig 3. Survival of patients treated with and without calcium-channel blocker (CCB) therapy. Among patients treated with calcium-channel blocker therapy (red dashed line), the all-cause mortality at 5 years was 92.7% as compared with 85.4% for those without calciumchannel blockers (blue solid line; p 0.126). dissection in enlarged aortas. The poor condition of the aortic wall in these patients with small aortic diameters may theoretically also result in increased risks of aortic enlargement during follow-up after dissection. Unfortunately, the IRAD does not contain data regarding connective tissue disorders other than Marfan syndrome. However, a selection bias may have affected the results of our analysis as well, because large dissected aortas generally more often undergo aortic intervention, and therefore more frequently may have been excluded from analysis. Most patients with uncomplicated ABAD are managed with medical management alone. In the IRAD, 93% of ABAD patients were prescribed -blockers, and about 65% of patients received calcium-channel blocker therapy. We observed that those patients treated with calciumchannel blockers exhibited a significantly lower aortic expansion rate during follow-up after ABAD compared with those without calcium-channel blockers (0.5 mm/y versus 3.9 mm/y), even after adjusting for other risk factors. Calcium antagonists generally block the slow calcium channels, decreasing the influx of extracellular calcium, which results in suppression of the sinoatrial and atrioventricular nodes, vascular dilation with decreased blood pressure, and reduced cardiac contractility. Adequate blood pressure regulation and subsequent decreased pressure on the aortic wall through calciumchannel blockade may theoretically decrease risks of aortic enlargement. Decreased aortic expansion observed among patients treated with calcium-channel blockers might lead to a lower risk of aneurysm formation and rupture. A recent IRAD investigation showed that use of calcium-channel blockers was independently associated with improved survival during follow-up among the IRAD cohort of ABAD patients [24]. The present analysis with a smaller cohort of ABAD patients with available growth rates showed a similar trend toward decreased follow-up mortality among patients treated with calciumchannel blockers. Unfortunately, exact causes of death during follow-up were not available for all patients, so it remains unclear whether the survival benefit is related to

6 1228 JONKER ET AL Ann Thorac Surg EXPANSION OF THE DISSECTED AORTA 2012;94: decreased aortic expansion among patients treated with calcium-channel blockers. Although physicians cannot alter many predictive factors of aortic expansion found in the current analysis, such as demographic and morphologic characteristics of ABAD patients, medical therapy clearly could be prescribed after ABAD. However, the exact role of calciumchannel blockers in aortic dissection remains undefined at this moment, and caution is needed when interpreting the current observations. Additional research, preferably a randomized, controlled trial, may be needed to assess the exact benefits and potential adverse effects of calcium-channel blockers after ABAD before any recommendations can be made. The IRAD database contains the largest series of patients with ABAD to date, which provided a unique opportunity to investigate predictors of aortic expansion after aortic dissection. However, as with all observational studies, this investigation has limitations that must be kept in mind when the data are interpreted. The patient cohort that was analyzed in this study consisted of a subselection of ABAD patients in the IRAD. Descending aortic diameter measurements during follow-up were not always available, so the aortic expansion rate could not be calculated for all patients. The presence of a possible selection bias therefore cannot be excluded. Unfortunately, data related to the specific calciumchannel blockers prescribed, medication dosages, or patient adherence were not recorded in the IRAD, so we could not stratify for these variables. In addition, the mortality data available to us did not include information on the cause of death for all patients, so potential improvements in survival among patients who received calcium-channel blockers remain unexplained. We observed several factors that affected the aortic expansion rate during follow-up after ABAD. White race and a small initial aortic diameter were associated with increased aortic expansion during follow-up, and decreased aortic expansion was observed among women, patients with IMH, and those receiving calcium-channel blockers. These data raise the possibility that the use of calcium-channel blockers after ABAD may reduce the rate of aortic expansion, and therefore further investigation is warranted. The IRAD is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Mardigian Foundation, and Gore Medical Inc (Flagstaff, AZ). References 1. Elefteriades JA, Hartleroad J, Gusberg RJ, et al. Long-term experience with descending aortic dissection: the complication-specific approach. Ann Thorac Surg 1992;53: Golledge J, Eagle KA. Acute aortic dissection. Lancet 2008; 372: Masuda Y, Yamada Z, Morooka N, Watanabe S, Inagaki Y. Prognosis of patients with medically treated aortic dissections. Circulation 1991;84(5 Suppl):III Glower DD, Fann JI, Speier RH, et al. Comparison of medical and surgical therapy for uncomplicated descending aortic dissection. Circulation 1990;82(5 Suppl):IV Hata M, Shiono M, Inoue T, et al. Optimal treatment of type B acute aortic dissection: long-term medical follow-up results. Ann Thorac Surg 2003;75: Elefteriades JA, Lovoulos CJ, Coady MA, Tellides G, Kopf GS, Rizzo JA. Management of descending aortic dissection. Ann Thorac Surg 1999;67:2002 5; discussion Suzuki T, Mehta RH, Ince H, et al. Clinical profiles and outcomes of acute type B aortic dissection in the current era: lessons from the International Registry of Aortic Dissection (IRAD). Circulation 2003;108(Suppl 1):II Trimarchi S, Eagle KA, Nienaber CA, et al. Importance of refractory pain and hypertension in acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2010;122: Tsai TT, Fattori R, Trimarchi S, et al. Long-term survival in patients presenting with type B acute aortic dissection: insights from the International Registry of Acute Aortic Dissection. Circulation 2006;114: Tsai TT, Evangelista A, Nienaber CA, et al. Long-term survival in patients presenting with type A acute aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2006;114(1 Suppl):I Sueyoshi E, Sakamoto I, Hayashi K, Yamaguchi T, Imada T. Growth rate of aortic diameter in patients with type B aortic dissection during the chronic phase. Circulation 2004;110(11 Suppl 1):II Song JM, Kim SD, Kim JH, et al. Long-term predictors of descending aorta aneurysmal change in patients with aortic dissection. J Am Coll Cardiol 2007;50: Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000;283: Kimura N, Tanaka M, Kawahito K, Yamaguchi A, Ino T, Adachi H. Influence of patent false lumen on long-term outcome after surgery for acute type A aortic dissection. J Thorac Cardiovasc Surg 2008;136:1160 6, 1166.e Spark JI, Baker JL, Vowden P, Wilkinson D. Epidemiology of abdominal aortic aneurysms in the Asian community. Br J Surg 2001;88: Salem MK, Rayt HS, Hussey G, et al. Should Asian men be included in abdominal aortic aneurysm screening programmes? Eur J Vasc Endovasc Surg 2009;38: Sueyoshi E, Sakamoto I, Uetani M. Growth rate of affected aorta in patients with type B partially closed aortic dissection. Ann Thorac Surg 2009;88: Tsai TT, Evangelista A, Nienaber CA, et al. Partial thrombosis of the false lumen in patients with acute type B aortic dissection. N Engl J Med 2007;357: Powell JT, Sweeting MJ, Brown LC, Gotensparre SM, Fowkes FG, Thompson SG. Systematic review and meta-analysis of growth rates of small abdominal aortic aneurysms. Br J Surg 2011;98: Schlösser FJ, Tangelder MJ, Verhagen HJ, et al. Growth predictors and prognosis of small abdominal aortic aneurysms. J Vasc Surg 2008;47: Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. Ann Thorac Surg 2002;74(Suppl):S ; discussion S Pape LA, Tsai TT, Isselbacher EM, et al. Aortic diameter 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2007;116: Trimarchi S, Jonker FH, Hutchison S, et al. Descending aortic diameter of 5.5 cm or greater is not an accurate predictor of acute type B aortic dissection. J Thorac Cardiovasc Surg 2011;142:e Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol 2012;109:122 7.

7 Ann Thorac Surg JONKER ET AL 2012;94: EXPANSION OF THE DISSECTED AORTA 1229 Appendix IRAD Co-Principal Investigators Kim A. Eagle, MD, University of Michigan, Ann Arbor, MI; Eric M. Isselbacher, MD, Massachusetts General Hospital, Boston, MA; Christoph A. Nienaber, MD, University of Rostock, Rostock, Germany. IRAD Co-Investigators Eduardo Bossone, MD, National Research Council, Lecce, Italy; Alan Braverman, MD, Washington University School of Medicine, St. Louis, MO; Stefanos Demertzis, MD, Cardiocentro Ticino, Lugano, Switzerland; Giuseppe DiBenedetto, MD, San Giovanni e Ruggi, Salerno, Italy; Mark Ehrlich, MD, University of Vienna, Vienna, Austria; Arturo Evangelista, MD, Hospital General Universitari Vall d Hebron, Barcelona, Spain; Rossella Fattori, MD, University Hospital S. Orsola, Bologna, Italy; James Froehlich, MD, and Thomas Tsai, MD, University of Michigan, Ann Arbor, MI; Dan Gilon, MD, Hadassah University Hospital, Jerusalem, Israel; Alan Hirsch, MD, and Kevin Harris, MD, Minneapolis Heart Institute, Minneapolis, MN; G. Chad Hughes, MD, Duke University, Durham, NC; Stuart Hutchison, MD, St. Michael s Hospital, Toronto, Ontario, Canada; James L. Januzzi, MD, Massachusetts General Hospital, Boston, MA; Alfredo Llovet, MD, Hospital Universitario 12 de Octubre, Madrid, Spain; Truls Myrmel, MD, Tromsø University Hospital, Tromsø, Norway; Peter Oberwalder, MD, Medical School Graz, Graz, Austria; Patrick O Gara, MD, and Joshua Beckman, MD, Brigham and Women s Hospital, Boston, MA; Jae K. Oh, MD, Mayo Clinic, Rochester, MN; Linda A. Pape, MD, University of Massachusetts Hospital, Worcester, MA; Reed Pyeritz, MD, University of Pennsylvania School of Medicine, Philadelphia, PA; Udo Sechtem, MD, and Gabriel Meinhardt, MD, Robert- Bosch Krankenhaus, Stuttgart, Germany; P. Gabriel Steg, MD, Hôpital Bichat, Paris, France; Toru Suzuki, MD, University of Tokyo, Tokyo, Japan; Santi Trimarchi, MD, IRCCS Policlinico San Donato, San Donato, Italy. Data Management and Biostatistical Support Daniel C Montgomery, MS, Dean E. Smith, PhD, and Elise Woznicki, University of Michigan, Ann Arbor, MI. INVITED COMMENTARY Despite recent advances made in the knowledge of the natural history and prognosis of acute type B aortic dissection (ABAD), many questions still linger. In this way, the International Registry of Acute Aortic Dissection (IRAD) comprises a unique source of vital information that definitely is helping understand the long-term outcomes of such patients. In this cohort analysis [1], the findings are relevant and with likely straight clinical implications. The unexpected observation that patients with smaller aortas (aortic diameter 4 cm) exhibited increased aortic expansion over time compared to those with larger aortas (diameter 4 cm) still warrants a reasonable explanation, but going forward we must remember that those patients should be watched closely and more cautiously than previously thought. The use of calcium channel blockers was consistently able to retard the aorta diameter enlargement in the long-run; therefore, it has been a promising novel and important tool in our armamentarium for treating these patients. This information is in consonance with and strengthens previous publication [2] in which calcium channel blockers was independently associated with improved survival during follow-up among the IRAD cohort of ABAD patients. Furthermore, some findings challenge data from prior reports. The prognostic implications of false lumen partial thrombosis have been an object of controversy and a previous study from IRAD found this entity a significant predictor of postdischarge mortality, compared with false lumen patency [3]. However, this finding has been contradicted by the data presented herein, not confirming the higher mortality related to the increased aortic expansion among these patients. The possible increased follow-up mortality for those patients with partial false lumen thrombosis remains open and unexplained; therefore, further research is needed about its effect on the prognosis of ABAD. Walter J. Gomes, MD, PhD Cardiovascular Surgery Discipline Escola Paulista de Medicina Federal University of São Paulo Rua Botucatu, 740 São Paulo, Brazil wjgomes.dcir@epm.br References 1. Jonker FHW, Trimarchi S, Rampoldi V, et al. Aortic expansion after acute type B aortic dissection. Ann Thorac Surg 2012;94: Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol 2012;109: Tsai TT, Evangelista A, Nienaber CA, et al. Partial thrombosis of the false lumen in patients with acute type B aortic dissection. N Engl J Med 2007;357: by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc