acute aortic dissection ( aad ) is a lethal cardiovascular disease . despite continuing improvements in surgical and medical management , the 10-year survival rate in patients with type a aad has remained low at 53.467.7  % [ 15 ] . medical therapy to reduce blood pressure ( bp ) and heart rate in patients with aad is widely used . among medications , treatment with beta - blockers is reported as the key medical therapy by lowering both bp and cardiac contractility [ 68 ] . heart rate is simply used as a surrogate of the degree of antiadrenergic and anti - inotropic effect of the drug therapy . only one study has evaluated the efficacy of tight heart rate control in patients with type b aad , which showed that the probability of aortic event - free survival was significantly higher in the tight heart rate control group compared with the conventionally managed heart rate group . however , little evidence exists regarding the need for a reduction in postoperative heart rate after repair of type a aad . we conducted this study to evaluate whether a lower heart rate during the early postoperative phase improves the long - term outcomes after surgical repair of type a aad . we retrospectively reviewed 434 patients who underwent surgical repair of a type a aad at jichi medical university saitama medical center between 1990 and 2011 . operations were performed urgently in all patients within 14  days of the onset of symptoms . the ethics committee approved this study , and the requirement for informed consent was waived . patients who died within 6  days after surgery or had missing data , were excluded . aortic dissection was proven by enhanced computed tomography , and defined as according to the stanford and debakey classifications . we used data from the first operation during the hospitalization if more than one operation was performed . preoperative variables evaluated in this study include age , gender , smoking , past medical history ( hypertension , diabetes , dyslipidemia , chronic obstructive pulmonary disease , myocardial infarction , cardiac operation and bicuspid aortic valve ) , hypotension , aortic regurgitation , surgical parameters ( duration of cardiopulmonary bypass , aortic cross clamp time , use of deep - hypothermic circulatory arrest ) , and laboratory data ( hemoglobin and serum creatinine level ) . postoperative events and outcomes include : the need for reoperation , aortic rupture in the hospital , atrial fibrillation , renal replacement therapy , stroke , prolonged ventilation ( defined as the requirement ventilation for more than 48  h ) , tracheostomy , icu length of stay , hospital length of stay and in - hospital mortality . intravenous beta - blockers and/or calcium channel blockers were administered to reduce systolic bp  <  120  mmhg as initial therapy in the icu after surgical repair . intravenous medications were replaced by oral antihypertensive drugs including calcium channel blockers , beta - blockers , angiotensin - converting enzyme inhibitors , angiotensin receptor blockers and diuretics , as appropriate . the decision to give oral antihypertensive medications was at the discretion of the treating physician . heart rate and bp at 6 a.m. , 2 p.m. , and 8 p.m. daily during the hospitalization were recorded . based on the average heart rate on postoperative days 1 , 3 , 5 , and 7 , 434 patients were divided into four groups , a : < 70 beats per minute ( bpm ) , b : 7079  bpm , c : 8089  bpm , and d : > 90  bpm . follow - up data including survival time and cause of death once in every 3  years after repair of type a aad were obtained by mailing a questionnaire to all patients . if responses were not returned , we contacted the patient , the patient s family or the family physician by telephone . aortic events were defined as aortic rupture , secondary operation , endovascular stenting , late organ ischemia or sudden death . data are presented as mean    standard deviation , medians ( interquartile ranges , iqr ) or percentages , as appropriate . either chi - square or fisher s exact test was used for nominal variables , and one - way analysis of variance was used to compare continuous variables . the kruskal wallis test was used for nonparametric variables . a p value of < 0.05 was considered statistically significant . cox proportional hazard analysis was conducted to identify independent risk factors for 10-year mortality and aortic events . cumulative 10-year survival rate and aortic event - free rate stratified by heart rate were analyzed with kaplan  meier analysis using the log - rank test . we retrospectively reviewed 434 patients who underwent surgical repair of a type a aad at jichi medical university saitama medical center between 1990 and 2011 . operations were performed urgently in all patients within 14  days of the onset of symptoms . the ethics committee approved this study , and the requirement for informed consent was waived . patients who died within 6  days after surgery or had missing data , were excluded . aortic dissection was proven by enhanced computed tomography , and defined as according to the stanford and debakey classifications . we used data from the first operation during the hospitalization if more than one operation was performed . preoperative variables evaluated in this study include age , gender , smoking , past medical history ( hypertension , diabetes , dyslipidemia , chronic obstructive pulmonary disease , myocardial infarction , cardiac operation and bicuspid aortic valve ) , hypotension , aortic regurgitation , surgical parameters ( duration of cardiopulmonary bypass , aortic cross clamp time , use of deep - hypothermic circulatory arrest ) , and laboratory data ( hemoglobin and serum creatinine level ) . postoperative events and outcomes include : the need for reoperation , aortic rupture in the hospital , atrial fibrillation , renal replacement therapy , stroke , prolonged ventilation ( defined as the requirement ventilation for more than 48  h ) , tracheostomy , icu length of stay , hospital length of stay and in - hospital mortality . intravenous beta - blockers and/or calcium channel blockers were administered to reduce systolic bp  <  120  mmhg as initial therapy in the icu after surgical repair . intravenous medications were replaced by oral antihypertensive drugs including calcium channel blockers , beta - blockers , angiotensin - converting enzyme inhibitors , angiotensin receptor blockers and diuretics , as appropriate . the decision to give oral antihypertensive medications was at the discretion of the treating physician . heart rate and bp at 6 a.m. , 2 p.m. , and 8 p.m. daily during the hospitalization were recorded . based on the average heart rate on postoperative days 1 , 3 , 5 , and 7 , 434 patients were divided into four groups , a : < 70 beats per minute ( bpm ) , b : 7079  bpm , c : 8089  bpm , and d : > 90  bpm . follow - up data including survival time and cause of death once in every 3  years after repair of type a aad were obtained by mailing a questionnaire to all patients . if responses were not returned , we contacted the patient , the patient s family or the family physician by telephone . aortic events were defined as aortic rupture , secondary operation , endovascular stenting , late organ ischemia or sudden death . data are presented as mean    standard deviation , medians ( interquartile ranges , iqr ) or percentages , as appropriate . either chi - square or fisher s exact test was used for nominal variables , and one - way analysis of variance was used to compare continuous variables . the kruskal wallis test was used for nonparametric variables . a p value of < 0.05 was considered statistically significant . cox proportional hazard analysis was conducted to identify independent risk factors for 10-year mortality and aortic events . cumulative 10-year survival rate and aortic event - free rate stratified by heart rate were analyzed with kaplan  meier analysis using the log - rank test . twenty - six patients died within 6  days and data of 10 patients were missing , as shown in fig .  1 . among the remaining 434 patients , the median follow - up period was 52 ( iqr 16102 ) months . the mean age was 63.3    12.1  years , and the male : female ratio was 51:49 . preoperative comorbidities included hypertension ( 70  % ) , diabetes ( 6  % ) , dyslipidemia ( 18  % ) , chronic obstructive pulmonary disease ( 3  % ) , previous myocardial infarction ( 5  % ) , previous cardiac operation ( 1  % ) , marfan syndrome ( 3  % ) , bicuspid aortic valve ( 1  % ) , hypotension ( 29  % ) , and aortic regurgitation ( 12  % ) .fig . 1patients included in the study , and the schema for classification into study groups a , b , c and d , stratified by heart rate ( bpm - beats per minute ) patients included in the study , and the schema for classification into study groups a , b , c and d , stratified by heart rate ( bpm - beats per minute ) surgical procedures performed included hemi - arch replacement ( 23  % ) , aortic arch replacement ( 14  % ) , aortic valve replacement ( 1  % ) , aortic root replacement with bentall procedure ( 4  % ) , coronary artery bypass grafting ( 7  % ) , and entry resection ( 73  % ) . the durations of operation , cardiopulmonary bypass time , aortic cross clamp time , and deep - hypothermic arrest time were 371    128 , 146    52 , 103    39 , and 35    15  min , respectively . postoperative complications included prolonged ventilation ( > 48  h ) ( 40  % ) , atrial fibrillation ( 37  % ) , perioperative stroke ( 10  % ) , re - exploration for bleeding ( 6  % ) , need for renal replacement therapy ( 6  % ) , tracheostomy ( 4  % ) , and early postoperative aortic rupture ( 1  % ) . the 434 patients were divided into four groups for further analysis based on their heart rate , including 19 patients ( 4  % ) in group a ( heart rate < 70  bpm ) , 87 patients ( 20  % ) in group b ( 7079  bpm ) , 162 patients ( 37  % ) in group c ( 8089  bpm ) , and 166 patients ( 38  % ) in group d ( > 90  bpm ) . postoperative average systolic and diastolic bp were 121    10 , 69    7  mmhg , respectively . tables  1 and 2 showed baseline and perioperative details categorized by the heart rate group . significant differences between the four groups were seen in regard to dyslipidemia , preoperative serum creatinine , operative time , re - exploration for bleeding , atrial fibrillation , need for renal replacement therapy , prolonged ventilation , and postoperative average diastolic bp . icu length of stay and hospital length of stay were also significantly different among the groups by univariate analysis.table  1baseline characteristics of patients with type a acute aortic dissection categorized by heart rate ( n  =  434)variableheart rate ( bpm)<7070798089>90 
 p valuepatient number1987162166characteristics  male ( % ) 52.648.351.951.20.96  age ( years)65    1064    1063    1363    130.93  smoking ( % ) 47.449.448.145.20.91medical history  hypertension ( % ) 89.575.967.966.90.11  diabetes ( % ) 5.33.44.97.80.51  dyslipidemia ( % ) 15.832.211.716.30.001  copd ( % ) 01.12.54.80.41  previous myocardial infarction ( % ) 10.54.63.74.80.61  previous cardiac operation ( % ) 01.11.91.20.91  marfan syndrome ( % ) 01.13.13.00.87  bicuspid aortic valve ( % ) 02.30.60.60.45preoperative laboratory data  serum creatinine ( mg / dl)1.9    2.81.2    1.41.0    0.61.0 0.80.002  hemoglobin ( g / dl)12.4    2.012.1    1.812.3    2.012.3    1.90.75preoperative shock ( % ) 15.826.433.327.70.36preoperative ar ( % ) 10.511.59.915.10.56debakey classification  type i ( % ) 73.763.258.668.10.26  type ii ( % ) 5.311.516.77.20.05  type iiib retrograde ( % ) 21.123.024.124.70.98 
 copd chronic obstructive pulmonary disease , ar aortic regurgitationtable  2intraoperative and postoperative details and short - term outcomes of patients with type a acute aortic dissection categorized by heart ratevariableheart rate ( bpm)<7070798089>90 
 p valuesurgery characteristics  operation time ( min)351    125337    96363    114398    1500.003  cpb time ( min)148    72142    45142    48151    590.34  aorta cross clamp time ( min)106    50105    35101    34103    440.89  dhca time ( min)35    2035    1435    1434    160.99  hemi - arch replacement ( % ) 26.331.022.817.50.10  aortic arch replacement ( % ) 21.113.89.916.90.20  aortic valve replacement ( % ) 5.301.21.20.29  bentall ( % ) 03.44.93.60.89  cabg ( % ) 06.94.99.60.29  entry resection ( % ) 78.975.972.871.50.83re - exploration for bleeding ( % ) 01.14.39.60.024postoperative events  aortic rupture in hospital ( % ) 01.10.60.61.00  atrial fibrillation ( % ) 15.829.934.046.70.005  renal replacement therapy ( % ) 10.53.43.19.60.037  perioperative stroke ( % ) 10.58.08.613.30.49  prolonged ventilation ( % ) 47.432.633.850.00.008  tracheostomy ( % ) 04.63.73.00.85postoperative average sbp ( mmhg)118    9121    10121    11121    100.54postoperative average dbp ( mmhg)65    867    669    770    7<0.001short - term outcomes  icu stay ( days)5 ( 310)5 ( 47)5 ( 47)7 ( 510)<0.001  hospital stay ( days)20 ( 1531)20 ( 1628)23 ( 1830)25 ( 1935)0.005  hospital mortality ( % ) 02.35.64.20.63 
 cpb cardiopulmonary bypass , dhca deep - hypothermic circulatory arrest , cabg coronary artery bypass graft , sbp systolic blood pressure , dbp diastolic blood pressure baseline characteristics of patients with type a acute aortic dissection categorized by heart rate ( n  =  434 ) 
 copd chronic obstructive pulmonary disease , ar aortic regurgitation intraoperative and postoperative details and short - term outcomes of patients with type a acute aortic dissection categorized by heart rate 
 cpb cardiopulmonary bypass , dhca deep - hypothermic circulatory arrest , cabg coronary artery bypass graft , sbp systolic blood pressure , dbp diastolic blood pressure the postoperative medications are shown in table  3 . most patients in the study ( 91  % ) required at least one antihypertensive medication at the time of discharge , which included beta - blockers ( 54  % ) , angiotensin - converting enzyme inhibitors ( 11  % ) , angiotensin receptor blockers ( 32  % ) , calcium channel blockers ( 62  % ) , and diuretics ( 28  % ) . beta - blocker use was significantly associated with a lower heart rate ( p  <  0.001).table  3postoperative medicationsheart rate ( bpm)variabletotal<7070798089>90 
 p valuebeta - blockers  initiation within 7  days after operation ( % ) 52.173.770.658.232.7<0.001  at discharge ( % ) 53.868.468.259.539.0<0.001  ace inhibitors at discharge ( % ) 11.315.88.29.214.50.31arb at discharge ( % ) 32.252.644.728.127.00.006ccbs at discharge62.578.968.258.861.00.23diuretics at discharge27.626.314.127.535.20.004 
 ace angiotensin - converting enzyme , arb angiotensin receptor blocker , ccb calcium channel blocker postoperative medications 
 ace angiotensin - converting enzyme , arb angiotensin receptor blocker , ccb calcium channel blocker cumulative survival rate from the time of admission in all groups was 97  % at 1  month , 93  % at 1  year , 81  % at 5  years , and 67  % at 10  years . cumulative aortic event - free rate in all groups was 98  % at 1  month , 96  % at 1  year , 91  % at 5  years , and 79  % at 10  years . meier analysis reveals no significant differences among the groups ( a vs. b , p  =  0.815 ; a vs. c , p  =  0.335 ; a vs. d , p  =  0.415 ) , as shown in fig .  2 . the probability of being 10-year aortic event - free was also not significantly different among the groups ( a vs. b , p  =  0.269 ; a vs. c , p  =  0.352 ; a vs. d , p  =  0.261 ) , as shown in fig . cox proportional regression analysis for 10-year mortality showed that significant predictors of mortality include age [ hazard ratio ( hr ) 1.04 ; 95  % confidence interval ( ci ) 1.071.06 ; p  =  0.001 ] and perioperative stroke ( hr 2.30 ; 95  % ci 1.184.50 ; p  =  0.024 ) ( table  4 ) . neither stratified heart rate nor beta - blocker use was significant . only a diagnosis of marfan syndrome was a significant risk factor in that model ( hr 6.59 ; 95  % ci 2.5716.87 ; p  <  0.001).fig . 2kaplan  meier curves for overall 10-year survival in patients with type a acute aortic dissection , stratified by heart ratefig . 3kaplan  meier curves for 10-year aortic event - free survival in patients with type a acute aortic dissection , stratified by heart ratetable  4multivariate analysis of risk factors for 10-year mortality and aortic events 
 p valuehazard ratio95  % civariable10-year mortality  age0.0011.0381.0161.061  perioperative stroke0.0152.3021.1774.50310-year aortic events  marfan syndrome<0.0016.5912.57416.872 
 ci confidence interval kaplan  meier curves for overall 10-year survival in patients with type a acute aortic dissection , stratified by heart rate kaplan  meier curves for 10-year aortic event - free survival in patients with type a acute aortic dissection , stratified by heart rate multivariate analysis of risk factors for 10-year mortality and aortic events 
 ci confidence interval in this study , we examined the association of heart rate , stratified into four groups , in the early postoperative period with long - term outcomes after repair of type a aad . the key findings showed that there is no significant difference in 10-year survival among the four groups using kaplan  meier analysis , nor is there a difference in the probability of being 10-year aortic event - free . cox regression analysis showed that significant predictors of 10-year mortality include age and perioperative stroke . only a diagnosis of marfan syndrome was significant in the model for 10-year aortic events . neither stratified heart rate nor any medication was a significant predictor for both 10-year mortality and aortic events . patients with type a aad usually undergo surgical repair , and postoperative medical therapy is routinely given to stabilize the aortic wall and prevent aortic rupture and recurrent dissection . medical management of aad was proposed in classic studies in the 1960s [ 10 , 11 ] . in those studies , authors established two primary goals of medical therapy including reduction in bp and diminution of left ventricular ejection force ( dp / dt ) . among medications , beta - blockers have been a key drug for the control of both dp / dt and bp by reducing both the heart rate and bp . reasonable targets for heart rate and systolic bp have been less than 60  bpm and between 100 and 120  mm hg , respectively . until the present , however , use of these medical therapies for aad has not been supported by solid clinical evidence . there is only one study that investigated the effect of tight heart rate control in patients with type b aad . kodama and colleagues retrospectively collected 171 patients with type b aad treated medically in a single center between 1997 and 2005 . based on the average heart rate at 3 , 5 , and 7  days after the onset , patients were divided into a tight heart rate management group ( < 60  bpm , n  =  32 ) and a control group ( 60  bpm , n  =  139 ) . the main outcome of kaplan  meier analysis for aortic event - free survival ( median follow - up 27  months ) showed that the tight heart rate control group had a significantly higher rate of being aortic event - free than the conventional heart rate control group ( p  =  0.017 ) . in comparison , the current study did not show a significant difference in long - term outcomes when stratified by heart rate . while this discrepancy may be caused by physiologic differences between type a aad and type b aad , studies to date have not conclusively shown whether or not we need to further reduce the heart rate . in patients who underwent repair of type a aad , little was known about the effects of medical therapy on long - term survival [ 13 , 14 ] . in contrast , there have been several studies to evaluate the long - term outcomes of medical therapy in patients with type b aad [ 7 , 8 , 13 , 1517 ] . suzuki and colleagues   investigated the effects of medications on long - term outcomes in 1301 patients ( 722 with type a and 579 with type b ) using the international registry of acute aortic dissection ( irad ) database from 1995 with follow - up to 5  years . the results of multivariate analysis of 654 surgically treated patients with type a aad showed that beta - blocker use was significantly associated with lower mortality ( hr 0.47 , 95  % ci 0.250.90 , p  =  0.02 ) . calcium channel blockers and renin  angiotensin system inhibitors were not included in their model . there have been reports that calcium channel blockers use is significantly associated with improved outcomes for patients with type b aad [ 13 , 16 ] . regarding the present study , however , no other studies have shown a positive effect of long - term calcium channel blockers use on patients with type a aad . although renin  angiotensin system inhibitors might be useful in patients with marfan syndrome and aortic aneurysms [ 18 , 19 ] , no evidence exists regarding the effects of these medications on patients with type a aad . as previously mentioned , bp control is the other primary goal of medical therapy in patients with type a aad . a recent single - center study evaluated the impact of bp on 25-year outcomes following repair of type a aad between 1984 and 2009 . based on the bp at late follow - up , all 252 patients were divided into three groups : systolic bp  <  120 , 120140 , and > 140  mmhg . patients who maintained a systolic bp  <  120  mmhg had improved freedom from reoperation compared with those having a bp 120140 or > 140  mmhg ( p  <  0.001 ) by kaplan  meier analysis . the present study failed to show an association between postoperative systolic bp in the acute phase and , either 10-year mortality , or being aortic event - free , by cox regression analysis . although , we have not been able to investigate the effect of the late - phase bp in the type a aad patients reviewed here , late follow - up of bp might be an important factor in addition to postoperative bp . marfan syndrome is one of the major inherited connective tissue disorders that may lead to the weakening of the aortic media , and subsequently to aad , aortic aneurysm or rupture . previous clinical trials showed that marfan syndrome was one of the risk factors for late aortic events [ 20 , 21 ] . in the current study , marfan syndrome was included among the risk factors for the occurrence of long - term aortic events . this might be partially explained by the fact that the dissected aortic wall in patients with marfan syndrome tends to develop aneurysmal dilatation due to wall weakness , more than in type a aad patients . most importantly , we evaluated only the acute phase of the average heart rate and bp on postoperative days 1 , 3 , 5 , and 7 , and we did not investigate the heart rate , bp or medications during long - term follow - up . approximately , half of the patients after discharge are followed at regular hospital visits , and the remaining patients are followed in other hospitals or clinics . thus , data for only about half of the patients regarding heart rate , bp , and medications are available after discharge from the hospital . the time points during the acute postoperative period may not be adequate surrogates for long - term control of heart rate , because the long - term heart rate and bp are probably different compared to those in the immediate postoperative period . these parameters may contribute to the failure to show a long - term difference in survival . although the sample size is not small compared with previous studies reporting long - term outcomes in patients with type a aad [ 15 , 20 , 2325 ] , these findings may be limited in application to other type a aad patients because of the relatively homogenous population . thirdly , the control of heart rate was not sufficient in our population because no one achieved less than 60  bpm and only 19 patients were less than 70 . although patients with beta - blockers tended to have a lower heart rate as shown in table  3 , it is difficult to reduce the heart rate after surgical repair due to multiple factors including , inflammation , infection , and atrial fibrillation . fourthly , class effects and dosages of the each medication were not reviewed in this study . we did not test the effect of the combination of drugs that might have more synergy . it is acknowledged that the medication list at the time of discharge may not adequately reflect long - term medication usage in the study population . we did not observe a difference in the long - term mortality or incidence of aortic events in patients after repair of type a aad , when stratified by heart rate during the acute hospitalization .
little evidence exists regarding the need for a reduction in postoperative heart rate after repair of type a acute aortic dissection . 
 this single - center retrospective study was conducted to determine if lower heart rate during the early postoperative phase is associated with improved long - term outcomes after surgery for patients with type a acute aortic dissection . 
 we reviewed 434 patients who underwent aortic repair between 1990 and 2011 . 
 based on the average heart rate on postoperative days 1 , 3 , 5 , and 7 , 434 patients were divided into four groups , less than 70 , 7079 , 8089 , and greater than 90 beats per minute . 
 the mean age was 63.3    12.1  years . during a median follow - up of 52  months ( range 16102 ) , 
 10-year survival in all groups was 67  % , and the 10-year aortic event - free rate was 79  % . 
 the probability of survival and being aortic event - free using kaplan 
 meier estimates reveal that there is no significant difference when stratified by heart rate . 
 cox proportional regression analysis for 10-year mortality shows that significant predictors of mortality are age [ hazard ratio ( hr ) 1.04 ; 95  % confidence interval ( ci ) 1.071.06 ; p  =  0.001 ] and perioperative stroke ( hr 2.30 ; 95  % ci 1.184.50 ; p  =  0.024 ) . 
 neither stratified heart rate around the time of surgery nor beta - blocker use at the time of discharge was significant . 
 there is no association between stratified heart rate in the perioperative period with long - term outcomes after repair of type a acute aortic dissection . 
 these findings need clarification with further clinical trials .