Quality of life following surgical repair of acute type A aortic dissection: a systematic review

Acute Type A aortic dissection (ATAAD) represents a cardiothoracic emergency. Conventional wisdom dictates that mortality rate increases 1–2% per hour within the initial 48 h, with the postoperative 30-day mortality varying between 10 and 35% [1, 2]. ATAAD is additionally associated with a high morbidity rate, with a range of postoperative sequelae such as stroke, prolonged intubation, myocardial ischemia, mesenteric ischemia, limb ischemia and renal failure [3‐5]. Long-term data suggests that the 10-year survival rate post-surgery is 50% [6‐8].

The outcomes of surgery for ATAAD extend beyond mortality and morbidity rates. Postoperative health-related quality of life (HR-QOL) provides information on the physical, mental, emotional and functional well-being of patients following surgery. HR-QOL research is well validated within cardiac surgery, with the Short Form 36 (SF36) being the most common questionnaire [9, 10]. Existing systematic reviews suggest positive HR-QOL outcomes following cardiac surgery [11, 12]. Evidence is accumulating that demonstrates diminished quality of life after surgery for ATAAD [13‐29]. Of note, elderly patients demonstrate a significantly higher mortality rate and lower quality of life following surgery.

This systematic review aims to summarise the literature surrounding HR-QOL following surgery for ATAAD, compare the outcomes to the standardised population, and assess the impact of age on HR-QOL outcomes following surgery.

The literature search identified 54 studies. An additional two articles were identified on manual searches of reference lists. After exclusion of irrelevant studies, 27 articles were deemed appropriate to undergo full-text review. Seventeen studies with a total of 2,388 patients were deemed suitable for inclusion for qualitative analysis in this review [13‐29]. Three studies were prospective, and the remaining 14 were retrospective cohort studies. Included studies had varying final cohorts from 12 to 210 patients. The majority of studies assessed all age groups and four studies assessed HR-QOL in the elderly. These results along with study quality is summarised in Additional file 1: Table S2.

Quality of life is a useful indicator of overall health as it captures information on the physical and mental health status of a patient. This provides a comprehensive assessment of the burden of disease. Evidence is mounting that HR-QOL outcomes are under utilised and have merit in assessing outcomes in cardiac surgical patients [10]. There is a paucity of literature assessing HR-QOL outcomes in patients who have undergone surgical repair of ATAAD [10].

Study heterogeneity and variability of reporting prevented direct comparison of results. The primary outcome of four studies was to report patients undergoing surgery for thoracic aortic aneurysm with aortic dissection being a subset of patients included in the analysis [16, 26‐28]. Three studies exclusively assessed elderly patients undergoing surgery for ATAAD [15, 18, 24]. HR-QOL outcomes were also variably reported. The majority of studies utilised SF-36 or SF-12 [13‐21, 25, 26, 28]. Within this, there was still variability with reporting of SF domains, with some papers utilizing MCS and PCS scores whereas others reporting individual domains. One of the included studies utilised the EQ-5D scale [22] whilst another utilised PROMIS [27]. Three included studies utilised a non-standardised HR-QOL outcomes, which makes direct comparison to standardised cohorts unattenable [23, 24, 29]. Baseline variables were also variably reported, with a number of studies not reporting operative practices, the use of DHCA or cerebral perfusion strategies. These may have an impact on postoperative QOL. The variability of reporting and differences in baseline variables was also a limiting factor for meta-analysis.

The majority of studies were retrospective with only three studies being prospective [14, 17, 27]. The retrospective design has inherent bias and contributes to a lack of data on whether these patients improved from their preoperative state and by what magnitude. Retrospective design also introduces recall bias, reducing the integrity of patient responses.

The HR-QOL over time is an important measure. Existing research in HR-QOL outcomes in cardiac surgery demonstrate that long-term follow up is required to truly evaluate the impact of an intervention [11, 41, 42]. Seven studies measured the change in HR-QOL over time [14, 16, 23‐25, 27, 29]. Only two included studies assessed the change in HR-QOL over the short and long term [14, 25]. Of mention, Endlich et al. prospectively measured postoperative MCS and PCS scores, providing valuable long-term data [14].

Three studies included in the current review measured preoperative scores in comparison to postoperative scores, which provides a valuable insight into the impact of surgery on these patients [16, 24, 29]. Of note, St Pierre et al. utilised SF36 and included over 100 patients in the final analysis [16]. Only four studies provide long term data (greater than 5 years postoperatively), highlighting the paucity of long-term outcomes [14, 15, 19, 25].

According to previous guidelines, a follow up rate of > 85% is considered ideal in systematic reviews [43]. None of the studies we evaluated attained this. This is understandable, as there was significant attrition due to mortality and morbidity associated with ATAAD surgery. This produces a selection bias; patients who do not participate in QOL assessment or those lost to follow-up potentially have worse QOL because of a greater burden of comorbidities, physical impairments, and psychological disturbance [44]. Studies with significantly low response rates are therefore more likely to skew the QOL results positively [44]. A number of studies had resultant small patient numbers [15, 17, 22, 24, 25]. Only four of the included studies incorporated greater than 100 patients [13, 16, 19, 21].

Well-designed prospective studies are required to make reliable conclusions on the HR-QOL outcomes after surgery for acute TAAD. These studies should utilise a standardised HR-QOL questionnaire such as SF-36 and make preoperative to postoperative comparisons along with long-term follow up. We appreciate that there are obstacles to this, as patients in the peri-operative setting are either unwell or the time critical nature of surgery prevents lengthy questionnaires. Furthermore, the mortality and morbidity of emergent ATAAD surgery produces attrition of follow up. As a result, the strength of evidence reviewed is limited.

HR-QOL outcomes are adversely affected in the postoperative period [14, 16, 24, 27, 29]. This result is not surprising, as ATAAD is associated with significant long-term morbidity. A recent study from the International Registry of Aortic Dissection found that 18% of patients had new renal insufficiency, 10% had new limb ischemia and 10% had major brain injury [45]. Four included studies assessed the change in HR-QOL over the operative period [16, 23, 24, 29]. Notably, three of these studies demonstrated that physical domains were significantly worse off postoperatively [16, 24, 29]. Studies that followed patients over the postoperative period also demonstrate impaired HR-QOL outcomes [14, 27]. Endlich et al. prospectively assessed 59 patients over the postoperative course [14]. The salient feature of this study was its long-term follow-up, which demonstrated significant attrition of both mental and physical health scores [14]. The loss of physical health over multiple time points provides a snapshot of the chronic course of the disease. Close to 20% of patients will require re-intervention within 5 years highlighting the chronic nature of the disease [46, 47]. Furthermore, a large portion of patients sustain a loss of function [48]. This takes an understandable toll on the physical health of patients and can account for the attrition of physical scores over time. Three studies suggest that mental health domains of patients, whilst initially affected, demonstrate some improvement over time. Notably, Sbarouni et al. demonstrated that that MCS scores at late time points are significantly higher than early timepoints [25]. Norton et al. demonstrated that 37% of patients reported severe anxiety in the postoperative period, reducing to 16% at late time points. These results reflect the emotional toll following emergency surgery and the adaptations patients make during the recovery phase.

Patients demonstrate worse HR-QOL outcomes following surgery when compared to age matched cohorts [13, 14, 18, 19, 26]. Four of the seven studies demonstrate significant impairment in physical domains after ATAAD repair [13, 14, 19, 26]. Two studies also demonstrate significant impairment in MCS scores [13, 14]. The largest of these studies was by Adam et al., which demonstrated that PCS scores were significantly lower than the norm sample across all age groups. This result is expected; ATAAD is an emergent disease and intervention is a life and death decision. Those that survive discharge out of hospital face challenges with recovery. Patients undergoing elective cardiac surgery on the other hand demonstrate a benefit in HRQOL over time. A systematic review of HR-QOL outcomes in aortic valve replacement demonstrate that the operative cohort do significantly better than age adjusted norm samples [11]. When considering aortic surgery, elective aortic surgery carries less risk than when procedures are done emergently [49]. As such, HR-QOL. outcomes in this setting fare well when compared to age matched cohorts [50]. This is consistent with other reviews investigating emergent aortic surgery. A systematic review by Shan et al. highlighted that the quality of life after emergent open abdominal aortic aneurysm repair was significantly worse than when the procedure is done electively and endoluminally [44].

Studies that assessed elderly cohorts of patients undergoing emergent surgery for ATAAD demonstrated attrition in HR-QOL outcomes postoperatively [13, 14, 20, 24, 29]. Of these included studies, two robust studies suggested that advancing age is associated with significantly worse PCSs postoperatively [13, 14]. The trend towards lower PCSs in the elderly is also demonstrated in other papers, albeit less robust [20, 24, 29]. Elderly patients are more likely to face major adverse cardiac and cerebrovascular sequalae after emergent surgery. One reason for this is that they are more vulnerable to the cerebral insult from deep hypothermic circulatory arrest which is required for some ATAAD repairs. As a result, the elderly cohort are more prone to lasting physical limitations compared to younger patients. Interestingly, two studies suggest that emotional well-being may be better in the elderly cohort compared to younger cohorts [13, 20]. While Endlich et al. demonstrated significantly lower MCSs in the elderly when compared to an age matched sample, they also demonstrated that younger patients have significantly worse MCSs by comparison [14]. For younger patients and their social environment, coping with the sequalae of an ATAAD is uncommon and more stressful. Younger patients often lose their job or require occupational training which is not the case for the elderly cohort. The combination of these may be attributable to the impact of MCSs, especially true in younger patients [14].

The sequelae of ATAAD poses an emotional toll on patients. This can lead to depressive disorders, PTSD and anxiety and are all linked with a loss of function [13, 21, 27]. Adam et al. demonstrated that one third of patients demonstrated symptoms of PTSD postoperatively and this was linked to diminished HR-QOL outcomes [13]. Luo et al. identified that sexual dysfunction was evident in 40% of patients postoperatively, with a significant impact on mental health in the younger population [21]. The survivors of ATAAD may benefit from psychological therapy in the postoperative setting, and those that are young or have been physically impaired as a result of the disease are particularly vulnerable.

The presence of preoperative neurological sequelae and malperfusion increases mortality and may negatively impact postoperative HRQOL. Bojko et al. demonstrated a significant association between malperfusion and mortality, which was most apparent in the elderly cohorts [15]. Only Schachner et al. reported the impact of malperfusion on postoperative HR-QOL, and found that patients with preoperative neurological symptoms and malperfusion had significantly lower postoperative activity [23].

Operative technique can affect the HR-QOL outcomes of patients with an ATAAD. The use of DHCA has been linked with poorer postoperative QOL in one study [28]. Findings suggest near normal HR-QOL postoperatively when DHCA is avoided or when ACP is used [26]. Distal anastomoses under DHCA may be favorable in certain circumstances, however DHCA is also associated with postoperative neurological sequalae and intraoperative coagulopathy, hence better HR-QOL when avoided. Larger prospective trials may validate this. The use of cerebral protection has been extensively studied from a mortality viewpoint, with multiple studies demonstrating a survival benefit from its use [51, 52]. Its translation to HR-QOL has not yet been validated; Endlich et al. did not demonstrate a significant QOL benefit from either perfusion strategy [14]. Ghazy et al. investigated the effects of an aggressive strategy with total arch replacement to a defensive strategy with ascending aorta replacement only and demonstrated longer operative times and potentially worse off physical function postoperatively [17]. Benefits of a defensive strategy include shorter cardiopulmonary bypass and circulatory arrest times, whereas an aggressive strategy may offer better long-term outcomes [17]. Short-term outcomes favour a defensive strategy, however there is still a paucity of long term data [17, 53]. Unless the clinical setting dictates an aggressive management strategy, a defensive strategy may be adopted with reasonable short-term HR-QOL outcomes [17].

HR-QOL outcomes are adversely affected when compared to preoperative status and physical health demonstrates significant attrition over time. HR-QOL outcomes are worse off when compared to an age matched general population. In terms of age, advancing age is associated with worse PCSs but emotional health may fare better than younger patients. To the authors’ knowledge, this is the only study to summarise HR-QOL literature in the setting of ATAAD. Well-designed prospective studies utilizing standardised HR-QOL measures would be of great value in drawing further conclusions.