Peri-procedural myocardial injury predicts poor short-term prognosis after TAVR: A single-center retrospective analysis from China

To the Editor: Approximately 2% of people >65 years old have aortic stenosis (AS).[1] Without intervention, AS is a rapidly progressive valvular heart disease with a 2-year mortality of 50%.[1] Since the first transcatheter aortic valve replacement (TAVR) was performed by Cribier et al[2] in 2002, TAVR has been suggested to be non-inferior in AS patients of various risk stratifications. Post-TAVR complications are essential in predicting patient survival and improving quality of life, especially with the procedure being performed in an increasing population of low-risk patients.[3] Among them, myocardial infarction (MI) is a rare but life-threatening complication usually caused by the obstruction of coronary ostia.[1] In comparison, peri-procedural myocardial injury, primarily characterized by the elevation of cardiac markers, is a relatively common complication of TAVR. Although recent studies have demonstrated promising results of cardiac markers in predicting cardiovascular adverse events, the impact of peri-procedural myocardial injury on short-term and long-term mortality has yet to be established. This study aimed to determine in-hospital, 30-day, and 1-year outcomes of TAVR patients who developed peri-procedural myocardial injury compared to patients without myocardial injury and identify factors associated with peri-procedural myocardial injury and its impact on the prognosis of TAVR patients. The study was approved by the Ethics Committee of Sichuan University West China Hospital (No. 2020–470). All patients provided written informed consent. The eligibility criteria, participants enrollment, statistical analysis, and TAVR procedure and follow-up were shown in Supplementary Materials, https://links.lww.com/CM9/B724. Compared with patients who had no myocardial injury after TAVR, patients who developed myocardial injury were older (75.0 [70.5–79.0] years vs. 74.0 [69.0–77.0] years, P = 0.005), weighed less (55 [49–62] kg vs. 59 [51–65] kg, P = 0.017), and had a higher STS score (7.8 [4.9–10.6] vs. 6.2 [4.0–8.7], P <0.001). There were no significant differences between the two groups in terms of comorbidities, including coronary artery disease (41.3% [81/196] vs. 37.2% [106/285], P = 0.361), prior percutaneous coronary intervention (PCI, 11.7% [23/196] vs. 8.1% [23/285], P = 0.179), hypertension (46.9% [92/196] vs. 43.9% [125/285], P = 0.505), diabetes mellitus (20.4% [40/196] vs. 18.2% [52/285], P = 0.553), chronic obstructive pulmonary disease (COPD, 54.1% [106/196] vs. 57.9% [165/285], P = 0.407), peripheral artery disease (43.4% [85/196] vs. 44.2% [126/285], P = 0.855), cerebrovascular disease (24.0% [47/196] vs. 18.6% [53/285], P = 0.153), chronic kidney disease (12.2% [24/196] vs. 7.4% [21/285], P = 0.071), and atrial fibrillation (18.9% [37/196] vs. 15.1% [43/285], P = 0.273). A large portion of the included patients had a bicuspid aortic valve (BAV, 48.0% [231/481]). A total of 85.7% (412/481) of the patients had an New York Heart Association (NYHA) Functional Classification of III/IV [Supplementary Table 1, https://links.lww.com/CM9/B724]. Supplementary Table 2, https://links.lww.com/CM9/B724 presented the results of pre-TAVR blood tests, patients who developed peri-operative myocardial injury exhibited higher levels of WBC count (6.31 [5.32–7.78] × 109/L vs. 6.01 [4.95–7.36] ×109/L, P = 0.020), AST (25 [20–33] IU/L vs. 24 [19–29] IU/L, P = 0.026), and creatinine (92.2 [76.0–114.5] μmol/L vs. 82.2 [71.0–101.0] μmol/L, P = 0.001), as well as lower levels of albumin (40.2 [37.0–42.7] g/L vs. 41.4 [38.7–44.0] g/L, P = 0.001), estimated glomerular filtration rate (eGFR, 62.6 [45.1–81.8] mL∙min-1∙1.73 m-2vs. 72.2 [57.5–84.2] mL∙min-1∙1.73 m-2, P = 0.002), triglyceride (1.05 [0.80–1.38] mmol/L vs. 1.16 [0.85–1.73] mmol/L, P = 0.019), cholesterol (3.74 [3.10–4.45] mmol/L vs. 4.09 [3.33–4.79] mmol/L, P = 0.004), and low-density lipoprotein (LDL, 1.98 [1.51–2.58] mmol/L vs. 2.3 [1.71–2.93] mmol/L, P <0.001). No significant difference was found in the blood coagulation test. Thoracic multislice computed tomography (MSCT) and echocardiography were used to assess the functional and anatomical characteristics. Baseline echocardiographic data were listed in Supplementary Table 3, https://links.lww.com/CM9/B724. A total of 70.7% (340/481) of the included patients had simple severe AS. A total of 28.3% (136/481) were concomitant with moderate or severe AR. No significant differences in left ventricular ejection fraction (LVEF, 62 [48–68] % vs. 60 [44–66] %, P = 0.131), maximum aortic valve velocity (4.9 [4.4–5.4] m/s vs. 4.8 [4.3–5.4] m/s, P = 0.577), and mean aortic valve gradient (59 [48–74] mmHg vs. 58 [46–74] mmHg, P = 0.664) were noticed between the two groups. Preprocedural MSCT assessment revealed similar anatomical characteristics of the aortic root. No significant difference was found in the aortic annulus, left ventricular outflow tract (LVOT), Sinus of Valsalva (SOV), height of coronary ostia, or calcific volume between the two groups (all P >0.05), except for the STJ long diameter (31.6 [28.3–35.2] mm vs. 30.1[28.3–33.4] mm, P = 0.034) [Supplementary Table 4, https://links.lww.com/CM9/B724]. Transfemoral access was taken among 99.6% (479/481) of the included patients. The Venus A valve was used in the majority of the patients (278/481, 57.8%) [Supplementary Table 5, https://links.lww.com/CM9/B724]. Valve-in-Valve (ViV) TAVR was more commonly performed in patients who developed myocardial injury (9.2% [18/196] vs. 3.9% [11/285], P = 0.015). In terms of intraprocedural complications, 11 (11/481, 2.3%) and 8 (8/481, 1.67%) patients developed ventricular fibrillation and atrial fibrillation, respectively. Patients who developed myocardial injury had a higher rate of intraprocedural bleeding (14.3% [28/196] vs. 5.3% [15/285], P = 0.001). Logistic analysis was performed to identify the potential causes of peri-procedural myocardial injury after TAVR [Supplementary Table 6, https://links.lww.com/CM9/B724]. In univariate analysis, we found that age, weight, Society of Thoracic Surgeons (STS) score, albumin, creatine, cholesterol, low-density lipoprotein cholesterol (LDL-C), hemoglobin, white blood cell (WBC) count, neutrophil count, left ventricular volume, interventricular septum thickness, and ViV implantation were potentially correlated with peri-procedural myocardial injury after TAVR. We used forward logistic regression analysis to adjust the interaction of the involved factors based on univariate analysis. Six factors finally formed the model to predict peri-procedural myocardial injury. Age (odds ratio [OR] 1.06, 95% confidence interval [CI, 1.01–1.12], P = 0.014), creatine (OR 1.01, 95% CI [1.00–1.02], P = 0.026), intraventricular septal width (IVS, OR 1.23, 95% CI [1.08–1.40], P = 0.002), ViV implantation (OR 3.99, 95% CI [1.10–14.52], P = 0.036), and bleeding (OR 3.66, 95% CI [1.19–11.26], P = 0.024) were independent risk factors for peri-procedural myocardial injury. Multivariate Cox analysis was performed to identify predictive factors for all-cause mortality. Included factors were based on univariate analysis and factors of interest. In this model, log troponin T elevation (cTnT) (hazard ratio [HR] 1.38, 95% CI [1.01–1.88], P = 0.045), age (HR 1.05, 95% CI [1.00–1.10], P = 0.044), and preprocedural creatine level (HR 1.00, 95% CI [1.00–1.01], P = 0.021) were independent risk factors for all-cause death after TAVR [Supplementary Table 7, https://links.lww.com/CM9/B724]. Sixty-eight (68/481, 14.1%) patients died in the entire cohort, among which 52 (52/481, 10.8%) were cardiac deaths. From the Kaplan–Meier survival curve [Figure 1], the risk of all-cause death in the myocardial injury group was 93% higher (HR 1.93, 95% CI [1.20–3.10], P = 0.006). No significant difference was found in cardiac mortality (HR 1.62, 95% CI [0.79–3.33], P = 0.185). Moreover, we found a 90-day landmark for all-cause mortality. We excluded patients who died within 90 days after TAVR and found no significant difference in all-cause mortality (HR 1.30, 95% CI [0.73–2.31], P = 0.366). According to the 90-day landmark, we obtained the predictive value of myocardial injury on post-TAVR mortality. As shown in Supplementary Table 8, https://links.lww.com/CM9/B724, within 90 days after TAVR, patients with myocardial injury had a 3.54-fold risk of death (HR 4.54, 95% CI [1.80–11.43], P = 0.001) and a 2.77-fold risk of cardiac death (HR 3.77, 95% CI [1.18–12.01], P = 0.025).Figure 1: Survival analysis after TAVR. (A) Survival curve of all-cause mortality after TAVR; (B) survival curve of cardiac mortality after TAVR; survival curve of all-cause mortality (C) and cardiac mortality (D) after TAVR, exclusion of participants died within 90 days after TAVR. CI: Confidence interval; HR: Hazard ratio; TAVR: transcatheter aortic valve replacement.The details of post-TAVR complications were shown in Supplementary Table 9, https://links.lww.com/CM9/B724. Bleeding was seen in 97 (97/481, 20.2%) patients, with 33 (33/481, 6.9%) of them having major bleeding. Twenty-one (21/481, 4.4%) patients developed thromboembolism, and eight (8/481, 1.7%) patients experienced stroke. A total of 135 (135/481, 28.1%) patients developed new-onset left bundle branch block (LBBB), and 89 (18.5%) patients underwent permanent pacemaker implantation (PPM). Rehospitalization occurred in 24 (24/481, 5.0%) patients, and the reason was heart failure in 8 (8/481, 1.7%) of them. Only one patient had MI after TAVR. Patients with perioperative myocardial injury were more likely to develop thromboembolic events (6.6% [13/196] vs. 2.8% [8/285], P = 0.044), stroke (3.1% [6/196] vs. 0.7% [2/285], P = 0.047), rehospitalization (8.2% [16/196] vs. 2.8% [8/285], P = 0.008), and rehospitalization due to heart failure (3.6% [7/196] vs. 0.4% [1/285], P = 0.007). In the survival analysis of this study, multivariate-adjusted cTnT level was found to be a risk factor for postoperative mortality (HR = 1.38, P = 0.045), and each unit increase in log cTnT was associated with risk of death increased by an average of 38% after TAVR. In addition, age and renal function are also important factors affecting the prognosis after TAVR. However, from the survival analysis, the difference between the two groups was mainly within 90 days after TAVR. After excluding participants who died within 90 days after TAVR, the survival rate and mortality risk between the two groups were no longer significantly different. That is, peri-procedural myocardial injury only increased the risk of death within 90 days after TAVR but had no significant effect on the risk of death once the patients survived 90 days after TAVR. Thus, the peri-procedural myocardial injury caused by TAVR impacts the patient in the acute phase. In clinical practice, we should closely monitor the cTnT level within 90 days after TAVR. Appropriate drug treatment should be given to enable the patient to benefit best from TAVR. The discussions on the factors associated with the peri-procedural myocardial injury can be reviewed in the Supplementary Materials, https://links.lww.com/CM9/B724. In conclusion, age, preprocedural creatinine level, ViV implantation, interventricular septal thickness, and intraprocedural bleeding are independent risk factors for myocardial injury after TAVR. Peri-procedural myocardial injury predicted short-term all-cause and cardiac death within 90 days after TAVR but have no apparent influence on those who survived 90 days after TAVR. Funding This study was supported by the National Natural Science Foundation of China (No. 82001899) and West China Hospital "1·3·5" Discipline of Excellence Project – "Mechanisms of aortic stenosis and the clinical applications".