Prognostic value of cardiac biomarkers in surgery for acute type A aortic dissection: mid-term follow-up results
Highlight box
Key findings
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed important prognostic value in not only short-term but also mid-term survival in patients undergoing surgery for acute type A aortic dissection (ATAAD). Cardiac troponin I (cTnI) was also associated with short-term mortality.
What is known and what is new?
• Previous research has indicated that positive cTnI is associated with short-term mortality in patients with ATAAD. Similar findings have been found for NT-proBNP, but there remains no consensus regarding its cut-off value.
• We found that positive cTnI and NT-proBNP ≥1,169.6 pg/mL were independent risk factors for short-term mortality, and that NT-proBNP ≥1,169.6 pg/mL was an independent risk factor for mid-term survival.
What is the implication, and what should change now?
• Both NT-proBNP and cTnI could serve as early biomarkers for the risk stratification of patients with ATAAD.
Introduction
Acute type A aortic dissection (ATAAD) is a life-threatening cardiovascular disease with extremely high mortality. The International Registry of Acute Aortic Dissection reported that 48-hour mortality remained as high as 23.7% and decreased to 4.4% following surgical treatment (1). A variety of risk indexes including biomarkers have been determined to help risk assessment of patients undergoing surgery for ATAAD. Cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are critical cardiac biomarkers and are routinely assessed in patients with ATAAD or patients presenting to the emergency department with chest pain. Therefore, cTnI and NT-proBNP testing is readily available for patients with ATAAD by nature of the current diagnostic set. Previous research has indicated that positive cTnI is associated with short-term mortality in patients with ATAAD (2,3). Similar findings have been found for NT-proBNP, but there remains no consensus regarding its cut-off value (4,5). Most importantly, no existing evidence investigates follow-up information, and thus it is still not clear whether cTnI or NT-proBNP has an impact on long-term survival in patients undergoing surgery for ATAAD.
The purpose of this study was to explore the association between cTnI and NT-proBNP and short- and mid-term survival in patients undergoing surgery for ATAAD. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1680/rc).
Methods
Patients
From April 2018 to December 2022, 574 consecutive patients underwent surgery for ATAAD at the Aortic and Vascular Center in Fuwai Hospital. The exclusion criteria were as follows: age under 18 years old; lack of preoperative cTnI levels; lack of preoperative NT-proBNP levels. Among them, 535 patients were retrospectively enrolled (Figure 1).
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committees of Fuwai Hospital (No. 2023-2061) and individual consent was waived due to the retrospective nature of the study.
Biomarker assay
Blood samples were collected and measured before surgery. cTnI and NT-proBNP were measured by an automated electrochemiluminescence immunoassay (Roche, Cobas e801, Basel, Switzerland). The given reference normal value of cTnI is below 0.02 ng/mL. Positive cTnI was defined as the level of cTnI ≥0.02 ng/mL. The lower limit value of the NT-proBNP test was 5 pg/mL; therefore, values less than that were recorded as 5 pg/mL for statistical analysis.
Definitions and endpoints
Coronary artery involvement was defined as Neri type B and type C determined on computed tomography angiography (CTA) which were dissection into the coronary artery with false lumen and circumferential detachment with an inner cylinder intussusception, respectively (6). Organ malperfusion was mainly defined according to the previous guideline (7) with some modifications. Cardiac malperfusion was defined as chest pain or positive troponin. Cerebral malperfusion was defined as coma or altered mental status. Mesenteric malperfusion was defined as abdominal pain or elevation of either aspartate aminotransferase or alanine aminotransferase over the upper range of normal. Renal malperfusion was defined as serum creatinine over the upper range of normal. Extremity malperfusion was defined as loss of pulses in ≥1 extremity or sensory or motor dysfunction. Malperfusion was defined as any of these organ malperfusions.
The primary endpoint was 30-day mortality. Paraplegia/paraparesis was defined as complete or partial loss of lower limb motor function related to spinal cord ischemia and not related to stroke until hospital discharge. Low cardiac output syndrome was defined as requiring an intra-aortic balloon pump or extracorporeal membrane oxygenation support. Renal failure was defined as renal dysfunction grade III according to the International Aortic Arch Surgery Study Group (8), which was serum creatinine increased by >3 times the baseline values or requiring temporary hemodialysis support for resolution. Urine output was not adopted in renal malperfusion or renal failure, for retrospectively collecting this data was of high inaccuracy.
Statistical analysis
Continuous variables were expressed as mean ± standard deviation or median (the first interquartile, the third interquartile) and assessed with Student’s t-test or Mann-Whitney U test. Categorical variables were expressed as count (frequency) and compared by Chi-squared or Fisher’s exact test. Restricted cubic curve analysis was performed to evaluate the relationship between cTnI and NT-proBNP level and 30-day mortality, respectively. Receiver operating characteristic (ROC) curve was used to explore the cut-off value of NT-proBNP for predicting 30-day mortality. Logistic regression analysis was performed to determine the risk factors for 30-day mortality. Kaplan-Meier curve and log-rank test were used to investigate the association between higher and lower cTnI and NT-proBNP groups and the mid-term survival, respectively. Cox proportional hazards analysis was performed to explore the risk factors for mid-term survival. In addition, the variable of cardiac malperfusion was not included in the multivariable analysis, for the definition of cardiac malperfusion included cTnI elevation, and thus they were strongly covariant.
All statistical tests were 2-tailed and P<0.05 was considered statistically significant. Statistical analysis was assessed using R version 4.0.4 (The R Foundation for Statistical Computing, Vienna, Austria).
Results
Among 535 patients undergoing surgery for ATAAD, there were 31 (5.8%) suffered from 30-day mortality. Table 1 presents the patient characteristics. Compared with the survivor group, the non-survivor group had older ages (57±13 vs. 51±12 years, P=0.01) and a higher incidence of cardiac malperfusion (54.8% vs. 27.8%, P=0.001). Both cTnI {0.022 [interquartile range (IQR), 0.005–0.093] vs. 0.006 (IQR, 0.002–0.027) ng/mL, P=0.002} and NT-proBNP [676 (IQR, 185–2,349) vs. 279 (IQR, 96–815) pg/mL, P=0.02] were significantly higher in the non-survivor group (Figure 2). Other baseline characteristics were all comparable.
Table 1
| Variable | All patients (n=535) | Survivors (n=504) | Non-survivors (n=31) | P value |
|---|---|---|---|---|
| Female | 136 (25.4) | 124 (24.6) | 12 (38.7) | 0.08 |
| Age (years) | 52±12 | 51±12 | 57±13 | 0.01 |
| BMI (kg/m2) | 27±4 | 27±4 | 26±5 | 0.89 |
| Hypertension | 446 (83.4) | 421 (83.5) | 25 (80.6) | 0.68 |
| Coronary artery disease | 114 (21.3) | 105 (20.8) | 9 (29.0) | 0.28 |
| Diabetes | 21 (3.9) | 18 (3.6) | 3 (9.7) | 0.22 |
| Marfan syndrome | 17 (3.2) | 17 (3.4) | 0 (0) | 0.62 |
| COPD | 6 (1.1) | 5 (1.0) | 1 (3.2) | 0.30 |
| Smoking | 225 (42.1) | 213 (42.3) | 12 (38.7) | 0.70 |
| History of cerebrovascular accident | 40 (7.5) | 35 (6.9) | 5 (16.1) | 0.13 |
| History of cardiac surgery | 13 (2.4) | 13 (2.6) | 0 (0) | >0.99 |
| cTnI (ng/mL) | 0.006 [0.002, 0.028] | 0.006 [0.002, 0.027] | 0.022 [0.005, 0.093] | 0.002 |
| Positive cTnI | 163 (30.5) | 145 (28.8) | 18 (58.1) | 0.001 |
| NT-proBNP (pg/mL) | 284 [97, 868] | 279 [96, 815] | 676 [185, 2,349] | 0.02 |
| Ejection fraction (%) | 60±4 | 61±4 | 60±5 | 0.68 |
| Aortic regurgitation (moderate/large) | 153 (28.6) | 144 (28.6) | 9 (29.0) | 0.96 |
| Coronary artery involvement on CTA | 34 (6.4) | 30 (6.0) | 4 (12.9) | 0.25 |
| Malperfusion | 245 (45.8) | 227 (45.0) | 18 (58.1) | 0.16 |
| Cardiac malperfusion | 157 (29.3) | 140 (27.8) | 17 (54.8) | 0.001 |
| Cerebral malperfusion | 26 (4.9) | 24 (4.8) | 2 (6.5) | >0.99 |
| Mesenteric malperfusion | 111 (20.7) | 102 (20.2) | 9 (29.0) | 0.24 |
| Renal malperfusion | 47 (8.8) | 43 (8.5) | 4 (12.9) | 0.61 |
| Extremity malperfusion | 41 (7.7) | 39 (7.7) | 2 (6.5) | >0.99 |
Values are presented as n (%), mean ± standard deviation, or median [interquartile range]. BMI, body mass index; COPD, chronic obstructive pulmonary disease; CTA, computed tomography angiography; cTnI, cardiac troponin I; NT-proBNP, N-terminal pro b-type natriuretic peptide.
Table 2 presents the intraoperative data and perioperative outcomes. The non-survivor group underwent more hybrid approach (29.0% vs. 10.9%, P=0.006) and coronary artery bypass grafting (45.2% vs. 23.8%, P=0.008), and experienced longer cardiopulmonary bypass time (280±141 vs. 192±66 min, P=0.002). The non-survivor group also had higher incidences of stroke (25.8% vs. 2.6%, P<0.001), paraplegia/paraparesis (12.9% vs. 3.0%, P=0.02), low cardiac output syndrome (12.9% vs. 0.8%, P=0.001), continuous renal replacement therapy (64.5% vs. 5.6%, P<0.001), and renal failure (74.2% vs. 10.5%, P<0.001), and had longer mechanical ventilation time [93 (IQR, 23–43) vs. 20 (IQR, 13–43) hours, P<0.001) and length of intensive care unit stay [9 (IQR, 4–16) vs. 4 (IQR, 3–7) days, P<0.001].
Table 2
| Variable | All patients (n=535) | Survivors (n=504) | Non-survivors (n=31) | P value |
|---|---|---|---|---|
| Main surgery | ||||
| Total arch replacement | 447 (83.6) | 425 (84.3) | 22 (71.0) | 0.052 |
| Partial arch replacement | 16 (3.0) | 16 (3.2) | 0 (0) | 0.62 |
| Hybrid approach | 64 (12.0) | 55 (10.9) | 9 (29.0) | 0.006 |
| Concomitant surgery | ||||
| Bentall procedure | 130 (24.3) | 122 (24.2) | 8 (25.8) | 0.84 |
| David procedure | 12 (2.2) | 12 (2.4) | 0 (0) | >0.99 |
| CABG | 134 (25.0) | 120 (23.8) | 14 (45.2) | 0.008 |
| CPB time (min) | 197±75 | 192±66 | 280±141 | 0.002 |
| Aortic cross-clamp time (min) | 119±41 | 118±41 | 132±40 | 0.07 |
| Perioperative outcomes | ||||
| Stroke | 21 (3.9) | 13 (2.6) | 8 (25.8) | <0.001 |
| Paraplegia/paraparesis | 19 (3.6) | 15 (3.0) | 4 (12.9) | 0.02 |
| Low cardiac output syndrome | 8 (1.5) | 4 (0.8) | 4 (12.9) | 0.001 |
| CRRT | 48 (9.0) | 28 (5.6) | 20 (64.5) | <0.001 |
| Renal failure | 76 (14.2) | 53 (10.5) | 23 (74.2) | <0.001 |
| Mechanical ventilation time (h) | 21 [14, 54] | 20 [13, 43] | 93 [23, 43] | <0.001 |
| Length of ICU stay (days) | 4 [3, 7] | 4 [3, 7] | 9 [4, 16] | <0.001 |
| Length of hospital stay (days) | 13 [10, 17] | 13 [10, 17] | 13 [8, 27] | 0.80 |
Values are presented as n (%), mean ± standard deviation, or median [interquartile range]. CABG, coronary artery bypass grafting; CPB, cardiopulmonary bypass; CRRT, continuous renal replacement therapy; ICU, intensive care unit.
The association between the cTnI and NT-proBNP with short-term mortality
Restricted cubic curve analysis showed that both cTnI (P for non-linearity=0.008) and NT-proBNP (P for non-linearity=0.030) presented a non-linear relationship with the 30-day mortality (Figure S1). ROC curve identified that the cut-off value of NT-proBNP for predicting 30-day mortality was 1,169.6 pg/mL [area under the curve: 0.628, 95% confidence interval (CI): 0.513–0.742, sensitivity: 45.2%, specificity: 83.3%] (Figure S2). Patients were then divided into the positive or negative cTnI group and NT-proBNP ≥1,169.6 pg/mL or NT-proBNP <1,169.6 pg/mL group, respectively.
The results of the univariate logistic regression analysis are shown in Table S1. Multivariable logistic regression analysis identified that positive cTnI [odds ratio (OR): 2.628, 95% CI: 1.148–6.016, P=0.02] and NT-proBNP ≥1,169.6 pg/mL (OR: 2.437, 95% CI: 1.050–5.654, P=0.04) were independent risk factors for 30-day mortality (Table 3).
Table 3
| Variable | OR (95% CI) | P value |
|---|---|---|
| Age | 1.022 (0.985–1.061) | 0.24 |
| Hybrid approach | 3.108 (1.151–8.393) | 0.03 |
| CABG | 1.138 (0.487–2.659) | 0.77 |
| CPB time | 1.009 (1.005–1.013) | <0.001 |
| Positive cTnI | 2.628 (1.148–6.016) | 0.02 |
| NT-proBNP ≥1,169.6 pg/mL | 2.437 (1.050–5.654) | 0.04 |
CABG, coronary artery bypass grafting; CI, confidence interval; CPB, cardiopulmonary bypass; cTnI, cardiac troponin I; NT-proBNP, N-terminal pro b-type natriuretic peptide; OR, odds ratio.
The association between the cTnI and NT-proBNP with mid-term survival
Follow-up was performed by outpatient visits combined with telephone consultations between December 2023 and July 2024. The completeness of follow-up was 100%, and the median follow-up period in this cohort was 3.3 (IQR, 2.2–4.7) years. Mid-term survival was worse in the patients with positive cTnI (log-rank P=0.006) and NT-proBNP ≥1,169.6 pg/mL (log-rank P<0.001), respectively (Figure 3). The results of the univariate Cox regression analysis are shown in Table S2. Multivariable Cox proportional hazards analysis identified that NT-proBNP ≥1,169.6 pg/mL (hazard ratio: 2.531, 95% CI: 1.323–4.843, P=0.005) rather than positive cTnI was an independent risk factor for mid-term survival (Table 4).
Table 4
| Variable | HR (95% CI) | P value |
|---|---|---|
| Age | 1.042 (1.012–1.074) | 0.006 |
| Coronary artery disease | 0.709 (0.319–1.575) | 0.40 |
| COPD | 4.372 (1.259–15.186) | 0.02 |
| Total arch replacement | 8,074.868 (0.000–NA) | 0.87 |
| Hybrid approach | 16,997.930 (0.000–NA) | 0.86 |
| CABG | 1.912 (0.824–4.438) | 0.13 |
| CPB time | 1.010 (1.007–1.013) | <0.001 |
| Aortic cross-clamp time | 0.990 (0.980–0.999) | 0.04 |
| Positive cTnI | 1.457 (0.784–2.707) | 0.23 |
| NT-proBNP ≥1,169.6 pg/mL | 2.531 (1.323–4.843) | 0.005 |
CABG, coronary artery bypass grafting; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; cTnI, cardiac troponin I; HR, hazard ratio; NA, not available; NT-proBNP, N-terminal pro b-type natriuretic peptide.
Discussion
The present study determined that the cut-off value of NT-proBNP for predicting short-term mortality was 1,169.6 pg/mL. Positive cTnI and NT-proBNP ≥1,169.6 pg/mL were significantly associated with short-term mortality. Patients with positive cTnI or NT-proBNP ≥1,169.6 pg/mL had worse mid-term survival. NT-proBNP ≥1,169.6 pg/mL was also an independent risk factor for mid-term survival.
Increasing efforts have been made to elucidate the prognostic value of cardiac troponin in patients with ATAAD. Research including a meta-analysis showed that positive cardiac troponin was significantly associated with short-term mortality in patients with acute aortic dissection (3,9). More precisely, a multicenter study and a cohort study including 1,321 patients with ATAAD both indicated that positive cTnI was an independent risk factor for short-term mortality and the prognostic value of a clinically based risk prediction model was significantly higher by adding the cTnI level (2,4). Consistently, positive cTnI was associated with short-term mortality in our cohort. Gong et al. revealed that preoperative high-sensitivity cTnI was not associated with 30-day mortality or mid-term survival (10). It was consistent with our findings of no significant association between cTnI as a continuous variable with 30-day mortality or mid-term survival, whereas positive cTnI had a significant impact. Furthermore, determining a cut-off value as positive cTnI had more clinically meaningful effects than solely proving this biomarker. In addition, we also found that patients with positive cTnI had worse mid-term survival than those with negative cTnI, which filled in the research gap on the role of positive cTnI in mid-term survival in patients undergoing surgery for ATAAD.
The release of cTnI into the blood is due to myocardial cell death. The primary etiology of cTnI elevation in patients with ATAAD is coronary malperfusion caused by the dissection of the aortic root retrogradely reaching the coronary artery, which was fully elucidated by Neri and colleagues (6). ATAAD might also induce cTnI elevation by hemodynamic aberrations including severe aortic regurgitation and increased blood pressure. Aortic regurgitation caused by ATAAD or other mechanisms leads to overloaded left ventricular volume and insufficient blood supply of the coronary arteries, resulting in subsequent myocardial ischemia and cTnI elevation (11,12). These pathophysiological alternations all portend poor outcomes in patients undergoing surgery for ATAAD and thus, preoperative results of cTnI exhibit a comprehensive effect of risk stratification. Of note, multivariable analysis showed that neither coronary artery involvement nor aortic regurgitation was associated with short- or mid-term mortality. Therefore, positive cTnI is a better indicator of high-risk patients than coronary artery involvement on CTA and aortic regurgitation.
Regarding NT-proBNP, a meta-analysis including 950 patients revealed that NT-proBNP was significantly associated with short-term mortality in patients with acute aortic dissection and that the cut-off values ranged from 312 to 647 pg/mL (5). The results were similar to ours, but we had a higher cut-off value (1,169.6 pg/mL). This disparity might be due to that the 4 studies included in this meta-analysis also enrolled patients without surgery, leading to a higher mortality and NT-proBNP concentrations compared with our cohort (short-term mortality: 11% vs. 5.8%; median NT-proBNP concentrations in non-survivors: 2,240 vs. 676 pg/mL). A multicenter study demonstrated that log-BNP was a significant predictor of in-hospital death in patients with ATAAD (4), whereas we found that NT-proBNP was not associated with short-term mortality. One possible interpretation for the paradox is the physiological difference between NT-proBNP and BNP. The former had a higher serum concentration, better physiological stability, and therefore, more commonly used in clinical testing than BNP. We found that patients with NT-proBNP ≥1,169.6 pg/mL had worse mid-term survival and that NT-proBNP ≥1,169.6 pg/mL was an independent risk factor for mid-term survival.
The expression of NT-proBNP is activated by the increased ventricular wall stress. The underlying mechanism of NT-proBNP increase in patients with ATAAD is similar to that of cTnI. Either ventricular volume expansion caused by severe aortic regurgitation or filling pressure overload caused by hypertension results in heart failure and the consequent secretion of NT-proBNP. In addition, renal dysfunction also contributes to the increase in serum NT-proBNP levels due to decreased renal clearance. Multivariable analysis identified that neither ejection fraction nor aortic regurgitation was associated with short- or mid-term mortality. Thus, NT-proBNP ≥1,169.6 pg/mL is more prognostically meaningful for risk stratification of patients undergoing surgery for ATAAD.
Study limitations
This was a retrospective study from a single center that was likely subject to selective bias. The generalizability of the results still needs further validation. Furthermore, this study only contained mid-term follow-up data. The impact of these cardiac biomarkers on long-term survival needs future investigation.
Conclusions
NT-proBNP showed important prognostic value in not only short-term but also mid-term survival in patients undergoing surgery for ATAAD. cTnI was also associated with short-term mortality. Both NT-proBNP and cTnI could serve as early biomarkers for risk stratification of patients with ATAAD.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1680/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1680/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1680/prf
Funding: This work was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1680/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committees of Fuwai Hospital (No. 2023-2061) and individual consent was waived due to the retrospective nature of the study.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Harris KM, Nienaber CA, Peterson MD, et al. Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection. JAMA Cardiol 2022;7:1009-15. [Crossref] [PubMed]
- Liu S, Song C, Bian X, et al. Elevated cardiac troponin I and short-term mortality in patients with acute type A aortic dissection. Eur Heart J Acute Cardiovasc Care 2022;11:597-606. [Crossref] [PubMed]
- Vrsalovic M. Prognostic effect of cardiac troponin elevation in acute aortic dissection: A meta-analysis. Int J Cardiol 2016;214:277-8. [Crossref] [PubMed]
- Yamamoto K, Saito Y, Hashimoto O, et al. Biomarkers for Risk Stratification in Patients With Type A Acute Aortic Dissection. Am J Cardiol 2024;212:103-8. [Crossref] [PubMed]
- Vrsalovic M, Vrsalovic Presecki A, Aboyans V. N-terminal pro-brain natriuretic peptide and short-term mortality in acute aortic dissection: A meta-analysis. Clin Cardiol 2020;43:1255-9. [Crossref] [PubMed]
- Neri E, Toscano T, Papalia U, et al. Proximal aortic dissection with coronary malperfusion: presentation, management, and outcome. J Thorac Cardiovasc Surg 2001;121:552-60. [Crossref] [PubMed]
- Isselbacher EM, Preventza O, Hamilton Black J 3rd, et al. 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2022;146:e334-482. [Crossref] [PubMed]
- Yan TD, Tian DH, LeMaire SA, et al. Standardizing clinical end points in aortic arch surgery: a consensus statement from the International Aortic Arch Surgery Study Group. Circulation 2014;129:1610-6. [Crossref] [PubMed]
- Li G, Wu XW, Lu WH, et al. High-sensitivity cardiac troponin T: A biomarker for the early risk stratification of type-A acute aortic dissection? Arch Cardiovasc Dis 2016;109:163-70. [Crossref] [PubMed]
- Gong M, Wu Z, Guan X, et al. Comparison of prognostic ability of perioperative myocardial biomarkers in acute type A aortic dissection. Medicine (Baltimore) 2019;98:e17023. [Crossref] [PubMed]
- Eggers KM, Lindahl B. Application of Cardiac Troponin in Cardiovascular Diseases Other Than Acute Coronary Syndrome. Clin Chem 2017;63:223-35. [Crossref] [PubMed]
- Bonaca MP, Reece TB. The prognostic implications of cardiac troponin in Type A aortic dissection and the challenge of understanding therapeutic consequences. Eur Heart J Acute Cardiovasc Care 2022;11:607-8. [Crossref] [PubMed]
