Current Role and Outcomes of Ascending Aortic Replacement for Severe Nonaneurysmal Aortic Atherosclerosis

Bartolo Zingone, MD, FETCS, Giuseppe Gatti, MD, Amedeo Spina, MD, Elisabetta Rauber, MD, Lorella Dreas, MD, Gabriella Forti, MD, and Aniello Pappalardo, MD Division of Cardiac Surgery, Ospedali Riuniti, Trieste, Italy

Background. Severe atherosclerosis of the ascending aorta is a challenging issue potentially affecting indications for surgery, operative choices, and patients’ outcome. No standard treatment has emerged to date, and uncertainties persist about criteria for selecting patients and procedures. Methods. Replacement of the atherosclerotic ascending aorta was performed in 64 patients at time of either aortic (n ⴝ 49), mitral (n ⴝ 21), or tricuspid (n ⴝ 7) valve surgery. Coronary artery bypass grafting was performed in 53 patients, and the majority of patients underwent combined procedures (n ⴝ 49). Mean age was 72.0 ⴞ 7.6 years. The expected operative mortality, by logistic European System for Cardiac Operative Risk Evaluation, was 29.0% accounting for ascending aortic replacement and 13.1% disregarding it. Circulatory arrest under deep hypothermia, eventually combined with either retro-

grade or antegrade brain perfusion, was required in 61 cases. Results. Early death, stroke, and myocardial infarction rates were 10.9%, 6.3%, and 7.8%, respectively. Factors univariately associated with early deaths were preoperative renal failure requiring dialysis (p ⴝ 0.001) and longer cardiopulmonary bypass (p ⴝ 0.001) and cardioplegia (p ⴝ 0.008) times. Cumulative survival at 1, 3, and 5 years was 86% ⴞ 4%, 74% ⴞ 6%, and 68% ⴞ 8%, respectively. Conclusions. Replacement of the atherosclerotic ascending aorta can be carried out at acceptable mortality rates despite the high rates of preoperative comorbidity and the significant incidence of postoperative complications.

S

previous studies provided no follow-up information and were mainly devoted to aortic valve replacement [6, 12–14], we thought it useful to review our own experience with a wider spectrum of conditions and the midterm follow-up of this procedure.

evere atherosclerosis of the ascending aorta in patients requiring cardiac surgery complicates the procedure and may jeopardize patients’ outcome. As an intraoperative unanticipated diagnosis, it may require that the planned procedure be converted to a no-clamp technique [1–5], although this would not be an attractive option for aortic valve replacement [6]. Things are no different when a diagnosis of porcelain aorta has been made preoperatively, except that the opportunity for surgery can be reassessed and some patients be simply declined. Alternatively, transcatheter aortic valve implantation [7, 8] and apicoaortic conduit implantation [9, 10] are now increasingly offered under these circumstances, although neither procedure is without limitations and risks. Ascending aortic replacement, first reported in the setting of severe atherosclerosis by Wareing and associates [11], has become our technique of choice when aortic valve replacement is required. It has also been used in a few more cases not amenable to less radical techniques despite the absence of aortic valve involvement. Because

Accepted for publication Nov 11, 2009. Address correspondence to Dr Zingone, 22 vicolo Scaglioni, 34141 Trieste, Italy; e-mail: [email protected].

© 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc

(Ann Thorac Surg 2010;89:429 –34) © 2010 by The Society of Thoracic Surgeons

Patients and Methods From July 2003 through October 2008, 64 of 3,017 (2.1%) consecutive patients operated on in our unit required resection of nonaneurysmal ascending aorta or aortic arch for severe atheroma. Relevant demographics and comorbidities are shown in Table 1. Criteria for assessing disease and deciding aortic replacement have not changed since our initial reports [15, 16]. Briefly, patients were screened by computed tomographic scan when ascending aortic calcium was noted on radiographs or coronary angiography. In addition, epiaortic ultrasonographic scanning was routinely performed at surgery. The ascending aorta was replaced when less radical alternatives were not feasible or appeared to be of questionable safety. Patients signed a detailed, informed consent when replacement of the ascending aorta was considered preoperatively. Otherwise, they gave a generic consent for technical changes as required by intra0003-4975/10/$36.00 doi:10.1016/j.athoracsur.2009.11.035

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Table 1. Demographics and Comorbiditiesa Variable ADULT CARDIAC

Age (y) Age ⱖ80 y Female sex Chronic obstructive pulmonary disease Diabetes Extracardiac arteriopathy Carotid arteriopathy Previous myocardial infarction (ⱕ3 months) Previous cardiac surgery Unstable angina NYHA III–IV CCS III–IV Priority nonelective Serum creatinine (mg/dL) Glomerular filtration rate (mL/min)b Chronic renal replacement therapy LVEF LVEF 0.30–0.49 LVEF ⬍0.30 Logistic EuroSCORE EuroSCORE without aortac a c

Number (%) or Mean ⫾ SD 72.0 ⫾ 7.6 12 (18.8) 17 (26.6) 15 (23.4)

Range 46–83

19 (29.7) 37 (57.8) 19 (29.7) 8 (12.5) 6 (9.4) 12 (18.8) 21 (32.8) 29 (45.3) 20 (31.3) 1.45 ⫾ 1.4 0.8–10 58 ⫾ 20 5–115 3 (4.7) 0.519 ⫾ 0.119 0.22–0.75 20 (31.3) 4 (6.3) 29.02 ⫾ 16.9 6.9–89.2 13.05 ⫾ 12.3 2.3–72.19

b Total number of patients (n ⫽ 64). Cockcroft-Gault formula. Estimated after withdrawal of the covariate “thoracic aortic surgery.”

CCS ⫽ Canadian Cardiac Society; EuroSCORE ⫽ European System for Cardiac Operative Risk Evaluation; LVEF ⫽ left ventricular ejection fraction; NYHA ⫽ New York Heart Association; SD ⫽ standard deviation.

operative findings. Approval for a retrospective data review study was granted by the ethics committee at the Ospedali Riuniti di Trieste. The cardiac procedures required in this series are common (Table 2). Technical details evolved somewhat and can be briefly summarized as follows. Basically, cardiopulmonary bypass was established through epiaortic ultrasonographic– guided cannulation of either the aorta or common brachiocephalic trunk, or axillary artery, in that order of preference. In most cases the aorta was not clamped before deep hypothermic circulatory arrest (DHCA) was initiated. The ascending aorta was resected, and an open distal anastomosis with a collagenimpregnated vascular graft was performed. Focal aortic endarterectomy was performed as needed to facilitate suturing. In most cases the superior vena cava was perfused retrogradely during DHCA to prevent air and debris from entering the brain circulation. The graft was then clamped, and all valve and/or coronary procedures were completed during rewarming. Resection of the ascending aorta was extended as needed to the root (n ⫽ 4) or to the proximal (n ⫽ 13) or distal arch (n ⫽ 5), depending on the availability of a suitable aortic edge for suturing. When reimplantation of arch branches was required they were reconstructed first by interposition

grafts, so that brain perfusion could be switched to the antegrade route by catheterizing the grafts and not the arteries. Placing clamps on arch branches was avoided and only in a few instances, early in the series, was the aorta temporarily occluded before DHCA. Replacement of the proximal aorta alone permitted distal crossclamping and avoidance of DHCA in 3 patients.

Data Acquisition and Analysis Clinical, procedural, and postoperative data were prospectively recorded into an institutional, supervised database and retrieved for this retrospective review. Deaths occurring within 30 days after surgery, or at any time during the hospital stay, were defined as early deaths. Stroke was defined as a new focal neurologic deficit or coma appearing during the postoperative stay and at least partially evident more than 24 hours after its onset. Nonfocal neurologic events, such as confusion and psychosis, were recorded as neurocognitive defects. Outcome data were reported both in aggregate and separately for four groups on the basis of procedural components. Patients in group A were candidates to simple aortic valve replacement requiring either no coronary revascularization or no more than a single coronary artery bypass graft (CABG). Group B included patients as above but with the need of multiple coronary grafts. Group C included patients with aortic and mitral valve surgery, eventually associated with tricuspid repair or coronary revascularization. Patients not requiring aortic valve surgery constituted group D. Individual probabilities of death were prospectively computed by the European System for Cardiac Operative Risk Evaluation (EuroSCORE) logistic model [17]. At the time of this analysis a hypothetical scenario excluding ascending aortic replacement was also simulated. This permitted a second set of EuroSCORE estimates withholding the variable “surgery of the thoracic aorta,” as if the aorta were normal and would not require attention. Categorical and continuous variables were compared by two-tailed Pearson’s ␹2 or Fisher’s exact tests as appropriate and nonparametric tests, respectively. Late survival was calculated by the Kaplan-Meier method (⫾1 standard error). Follow-up phone interviews were conducted by the authors in January 2009. Descriptive and inferential staTable 2. Cardiac Procedures Procedure AVR AVR, MVR AVR, MVR, TVR MVR MVR, TVR CABG Total

Number Without CABG

Number With CABG

8 2 1 ... ... ... 11

28 6 4 6 2 7 53

AVR ⫽ aortic valve replacement; CABG ⫽ coronary artery bypass grafting; MVR ⫽ mitral valve repair or replacement; TVR ⫽ tricuspid valve repair.

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Circulatory Arrest and Cerebral Perfusion Management No circulatory arrest Plain arrest, no cerebral perfusion Selective antegrade carotid perfusion Superior vena cava retrograde perfusion Retrograde with antegrade sequential brain perfusion Total

DHCA (min)

Brain Ischemia (min)

Antegrade Cerebral Perfusion (min)

Lowest Pharyngeal Temperature (°C)

165 ⫾ 39 100 ⫾ 32

... 15 ⫾ 13

... 15 ⫾ 13

... ...

31 ⫾ 0.6 24 ⫾ 5

231 ⫾ 47

164 ⫾ 41

35 ⫾ 10

2⫾2

33 ⫾ 8

18 ⫾ 4

41

230 ⫾ 59

155 ⫾ 42

26 ⫾ 11

26 ⫾ 11

...

20 ⫾ 3

6

293 ⫾ 50

203 ⫾ 39

96 ⫾ 36

38 ⫾ 11

58 ⫾ 37

17 ⫾ 5

64

232 ⫾ 62

158 ⫾ 45

34 ⫾ 26 (4–138)

22 ⫾ 15 (3–63)

41 ⫾ 26 (15–112)

20 ⫾ 4

n

CPB (min)

X-Clamp (min)

3 4

223 ⫾ 100 167 ⫾ 59

10

CPB ⫽ cardiopulmonary bypass time;

DHCA ⫽ deep hypothermic circulatory arrest;

tistics and survival curves were developed by SPSS 14.0 (SPSS Inc, Chicago, IL).

Results Details on duration of cardiopulmonary bypass, cardiac ischemia, circulatory arrest, and brain perfusion management are shown in Table 3. Seven patients (10.9%) died in the hospital 2 to 83 days after surgery. Four deaths occurred within 4 days (respiratory failure, low cardiac output, multiorgan failure, and mesenteric ischemia), and 3 more patients evolved through multiple complications to succumb 31, 74, and 83 days later of multiorgan failure, sepsis, and liver failure, respectively. The distribution of selected variables across survivorship is shown in Table 4. Indicators of preoperative renal dysfunction were univariately associated with the risk of early death, and none of the 3 patients receiving chronic renal replacement therapy survived. Thus, death rate was 6.6% among the 61 patients not requiring chronic renal replacement therapy preoperatively. No other preoperative variable was statistically associated with early deaths. Besides more frequent renal disease, patients dying in the hospital had significantly longer cardiopulmonary bypass and cardiac ischemia times (Table 4). Segmenting the series by the operative times showed that the boundaries between middle and upper tertiles, 248 minutes for cardiopulmonary bypass and 179 minutes for cardiac ischemia times, were associated with a steep rise of death rates up to 26.3% for cardiopulmonary bypass longer than the threshold (compared with 4.4%; p ⫽ 0.02) and 28.6% for cardiac ischemia longer than the threshold (compared with 2.3%; p ⫽ 0.006). The decision to replace the ascending aorta was taken preoperatively in 35 patients (54.7%) and might have also been anticipated in some of the remaining cases. Frequently, however, it was the ultrasonographic scanning of the aorta showing extensive soft atheromas (with a mobile component in 12 cases) that prompted the decision to replace the aorta. Neither differences of risk

X-clamp ⫽ cardiac ischemia time.

profile as estimated by logistic EuroSCORE nor duration of cardiopulmonary bypass, cardiac ischemia, or circulatory arrest attained significance among groups for time of decision. Time of decision did not seemingly affect the risk of early death either (Table 4). None of the 13 patients in whom the aorta was temporarily or permanently occluded died in the hospital. None of the 4 patients who underwent plain DHCA died or experienced neurologic complications. Early death and complication rates by procedural group are given in Table 5 for purely descriptive purposes. Death rate was higher in patients undergoing multiple valve surgery (group C), although only numerically so. No specific procedure was found to be significantly associated with risk variation. Postoperative complications occurred frequently, as detailed in Table 5. Neurocognitive disturbances uniformly cleared before discharge. Two patients with stroke were discharged without sequelae, but 2 more died early after surgery. Neurologic complications were no different between clamp compared with no-clamp cases as, among the former, 2 had transient cognitive disturbances and 1 experienced a stroke with no sequelae. Among patients not receiving chronic renal replacement therapy before surgery, those with a greater than 50% decrease of the glomerular filtration rate perioperatively (n ⫽ 15) experienced a significantly higher death rate compared with the others (n ⫽ 46), or 26.7% versus 0% (p ⫽ 0.003). The left ventricular ejection fraction at predischarge echocardiography in 55 survivors was 0.548 compared with 0.523 preoperatively (p ⫽ 0.05). In greater detail, it decreased from 0.554 ⫾ 0.141 to 0.476 ⫾ 0.145 in 13 patients, increased from 0.43 ⫾ 0.115 to 0.555 ⫾ 0.135 in 19 patients, and changed less than 0.04 points in the remaining patients, all but one within normal limits. Postoperative bleeding was significant and frequently required reexploration (Table 5). Cumulative survival at 1, 3, and 5 years was 86% ⫾ 4%, 74% ⫾ 6%, and 68% ⫾ 8%, respectively (Fig 1). The corresponding figures for a normal age- and sex-matched population would be 97%, 90%, and 82%. The causes of

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Table 3. Circulatory Arrest and Brain Perfusion Management

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Table 4. Association of Preoperative Variables and Operative Times With In-Hospital Deatha Variable ADULT CARDIAC

Age (y) Age ⱖ80 y Female sex Carotid artery disease Extracardiac arteriopathy Stroke Diabetes Chronic obstructive pulmonary disease Pulmonary hypertension Creatinine (mg/dL) GFR (mL/min) Creatinine ⱖ2.3 mg/100 mL Chronic renal replacement therapy Myocardial infarction ⬍3 months LVEF LVEF 0.30–0.49 LVEF ⬍0.30 NYHA III–IV CCS III–IV Unstable angina Urgent priority Previous surgery Unanticipated intraoperative decision Use of aortic cross-clamp Expected deaths (logistic EuroSCORE) Expected deaths without aorta (logistic EuroSCORE) Cardiopulmonary bypass time (min) Cardioplegia time (min) Arrest time (min) Brain ischemia time (min) a

Alive (n ⫽ 57)

Dead (n ⫽ 7)

p Value

71.8 ⫾ 7.5 19.3 29.8 29.8 57.9 8.8 31.6 24.6

73.6 ⫾ 8.7 14.3 0 28.6 57.1 14.3 14.3 14.3

0.3 1 0.17 1 1 0.52 0.66 1

0 1.17 ⫾ 0.2 60 ⫾ 18 0 0

14.3 3.67 ⫾ 3.52 40 ⫾ 28 42.9 42.9

0.11 0.12 0.11 0.001 0.001

10.5

28.6

0.2

0.52 ⫾ 0.12 33.3 5.3 28.6 43.9 15.8 29.8 10.5 47.4

0.49 ⫾ 0.11 14.3 14.3 33.3 57.1 42.9 42.9 0 28.6

0.3 0.42 0.38 1 0.7 0.11 0.67 1 0.4

22.8 27.5

0 41.3

0.33 0.34

11.8

23.5

0.34

222 ⫾ 55

309 ⫾ 64

0.001

152 ⫾ 41 33 ⫾ 23 22 ⫾ 15

204 ⫾ 49 41 ⫾ 45 25 ⫾ 13

0.008 0.7 0.8

Numbers are percentages or mean ⫾ standard deviation.

CCS ⫽ Canadian Cardiac Society; EuroSCORE ⫽ European System for Cardiac Operative Risk Evaluation; GFR ⫽ glomerular filtration rate; LVEF ⫽ left ventricular ejection fraction; NYHA ⫽ New York Heart Association.

the 8 late deaths were cancer, myocardial infarction, congestive heart failure, diabetic coma, acute renal failure, respiratory failure, complications from femoral fracture, and unknown, one each.

Comment Severe aortic atherosclerosis may preclude safe cannulation and cross-clamping and constitute a serious hindrance to aortotomies and suturing. A number of ways have been described to either deal with or circumvent

these difficulties while ensuring that the risks of cerebral embolism be minimized [18, 19]. In this regard isolated CABG procedures have been extensively investigated and are quite readily converted to an aortic no-touch approach [1–3, 19, 20]. It is patients with coexisting coronary artery and valve disease who constitute, however, a cohort at particularly high risk of atherosclerotic aorta [15, 16, 21, 22] with greater potential for perioperative stroke and, at the same time, posing special technical challenges. As for the surgical options available, data from previous reports of either endoaortic balloon clamping, aortic endarterectomy, or clampless aortic valve replacement have been inconsistent at best in regard to perioperative death and stroke rates [6, 13, 23–26]. Early experience with replacement of the atherosclerotic ascending aorta has not been uniformly successful either [6, 11, 12]. On the other hand, we, as others before [11, 13, 14], have been fortunate with our initial series of ascending aortic replacement procedures, possibly because of a more comprehensive approach with regard to accurate aortic atheroma mapping and vessel manipulation [15, 16]. Expectedly, the majority of patients in the current study underwent aortic valve replacement. When other cardiac valves were spared, and irrespective of whether CABG was also required (groups A and B), the 8.3% hospital mortality rate was numerically—and nearly significantly—lower than expected by EuroSCORE estimates, and midterm survival was similar to a normal ageand sex-matched population. The hospital complication rates were also reasonably low, with only 1 stroke in 36 patients. Results went different in patients presenting with multiple valve involvement and extensive coronary artery disease (group C). Mortality and complication rates were numerically higher in this group, and credibly so despite the lack of statistical significance, making alternative approaches worth consideration under these circumstances. In patients not requiring aortic valve surgery (group D), disregarding more conservative options in favor of ascending aortic replacement under DHCA cannot go without justification. Such a strategy was determined by the surgeon preoperatively in 2 of our 7 isolated CABG patients, while in the remaining 5 this strategy was decided on with the intraoperative finding of severe atheroma with a significant mobile component. All of them were discharged alive with no neurologic complication. With due consideration to the prevailing role of beating heart techniques for dealing with bad aortas in coronary operations, an approach we consistently use as our first choice in this setting, the presence of a mobile atheroma in the ascending aorta identifies a distinct minority of patients for whom a resectional approach may be preferable. Finally, in 8 patients undergoing mitral valve surgery, the operating surgeon recorded a large ventricle precluding optimal exposure, the need for extensive revascularization (mean number of grafts was 4.9), and the presence of a mobile component in 3 of them as the reason for such a choice.

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Variable Neurocognitive defect Stroke Myocardial infarction Postoperative blood losses (mL/m2) Reoperation for bleeding Acute renal failure GFR decrease ⬎25% & ⱕ50% GFR decrease ⬎50% & ⱕ75% GFR decrease ⬍75% Renal replacement therapyb Intubation ⬎48 h Intensive care unit LOS (days) Postoperative LOS (days) Hospital deaths Expected deaths Expected deaths without aorta

Total (n ⫽ 64)

Group A, Single AVR and 0–1 CABG (n ⫽ 18)

Group B, Single AVR and ⬎1 CABG (n ⫽ 18)

Group C, AVR With Multiple Valve Surgery ⫾ CABG (n ⫽ 13)

Group D, No AVR (n ⫽ 15)

8 (12.5) 4 (6.3) 5 (7.8) 815 ⫾ 717 10 (15.6)

2 (11.1) 1 (5.6) 2 (11.1) 723 ⫾ 765 2 (11.1)

2 (11.1) 0 0 784 ⫾ 741 2 (11.1)

0 1 (7.7) 2 (15.4) 899 ⫾ 607 4 (30.8)

4 (26.7) 2 (13.3) 1 (6.7) 889 ⫾ 771 2 (13.3)

26 (40.6) 13 (20.3) 2 (3.1) 3 (4.7) 15 (23.4) 11 ⫾ 28 20 ⫾ 32 7 (10.9) 18.6 (29.0) 8.4 (13.1)

6 (33.3) 2 (11.1) 1 (5.6) 0 2 (11.1) 4⫾4 14 ⫾ 11 1 (5.6) 4.1 (22.7) 1.9 (10.6)

12 (66.7) 1 (5.6) 0 0 3 (16.7) 8 ⫾ 19 16 ⫾ 17 2 (11.1) 5.1 (28.2) 2.1 (11.4)

2 (15.4) 7 (53.8) 0 2 (15.4) 5 (38.5) 14 ⫾ 22 22 ⫾ 21 3 (23.1) 4.5 (34.4) 2.2 (17.2)

6 (40) 3 (20) 1 (6.7) 1 (6.7) 5 (33.3) 21 ⫾ 50 32 ⫾ 60 1 (6.7) 4.9 (32.9) 2.1 (14.3)

a Numbers are absolute values (with % in brackets) or mean ⫾ standard deviation; expected death rate estimated by logistic EuroSCORE; patients b receiving chronic renal replacement therapy were 2 for group B and 1 for group C. Not required preoperatively.

AVR ⫽ aortic valve replacement;

CABG ⫽ coronary artery bypass grafts;

There are no data to comparatively assess the outcomes in our series, and we therefore used EuroSCORE [17] for this purpose. Because the 29% expected death rate as estimated by EuroSCORE was partly affected by our choice to replace the ascending aorta we also obtained a second set of estimates withholding that procedural variable. The 13% resulting figure suggests that our patients were at high risk independently from surgical strategy and that further accounting for the EuroSCORE’s trend to overestimate the risks [27] did not move the observed mortality rate away from acceptable levels. Postoperative complications were frequent in our series, prolonging hospital stay and increasing the consumption of costly resources, and also leading to fatal outcomes. In this regard it is worth noting the contribution that both preoperative and perioperative renal failure, together with long operative times, made to increase the rates of complications and deaths, although small

GFR ⫽ glomerular filtration rate;

LOS ⫽ length of stay.

numbers preclude any solid inference. It is questionable, however, whether current technology, namely transcatheter coronary and valve techniques or apicoaortic conduits, might have constituted an alternative for a few of our patients, actually for those few who might have needed it least. In fact, only 28% of our patients would have qualified for alternative approaches if they were to be selected on the basis of the aortic valve replacement being either isolated or associated with a single coronary graft, and those patients did well with surgery. Whether transcatheter valve and coronary combined procedures will ever progress to the point of constituting an alternative treatment for the most complex multivalve and multivessel disease patients is difficult to envision at this stage. We therefore suggest that replacement of the severely atherosclerotic aorta plays a major role in otherwise complex and high-risk patients, who should not be refused surgery or shifted to alternative procedures on a Fig 1. Kaplan-Meier cumulative survival for the whole series (A) and the four subgroups (B). Numbers are patients at risk. Lines represent single AVR with 0 –1 CABG (stars, Group A), single AVR with ⬎1 CABG (solid circles, Group B), AVR with multiple valve surgery (open circles, Group C), and no aortic valve surgery (squares, Group D). (AVR ⫽ aortic valve replacement; CABG ⫽ coronary artery bypass grafts.)

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Table 5. Postoperative Complications and Deathsa

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regular basis until current technologies have made further progress.

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