The platelet-to-lymphocyte ratio (PLR) is a novel inflammatory biomarker that has prognostic value in patients presenting with acute coronary syndrome. Transcatheter aortic valve implantation (TAVI) treats the inflammatory disease of aortic stenosis. However, the utility of preprocedure PLR in predicting major adverse cardiovascular events (MACE) after TAVI is not clear. Our study population included 470 patients who underwent TAVI at The Alfred Hospital in Melbourne, Australia from August 2008, to January 2019. Patients were divided into 4 groups based on PLR quartiles. The incidence of 30-day MACE (a composite of stroke, myocardial infarction, and death) was then compared. Outcomes were reported according to the Valve Academic Research Consortium-2 criteria. Of 470 patients, median age 84 years, 54% men, and median Society of Thoracic Surgeons score of 3.5%, 14 (3%) suffered a MACE within 30 days. Rates of MACE were low in all 4 groups (1.7%, 2.5%, 2.6%, 5.1%, respectively) with no statistically significant difference in the different PLR groups (p = 0.46). This nonsignificant association was supported by univariate logistic regression analysis of PLR as a continuous variable (odds ratio 1.01, p = 0.55). Using multivariable logistic regression analysis accounting for age, gender, self-expanding valve, and procedural risk, a higher PLR did not correlate with MACE (odds ratio 1.01, p = 0.60). In this study of a large cohort of TAVI patients, elevated preprocedure PLR was not independently associated with MACE after TAVI. This is a novel finding in comparison with previous studies.
Symptomatic, severe aortic stenosis portends a poor prognosis without intervention. In the last decade, transcatheter aortic valve implantation (TAVI) has emerged as a highly efficacious and safe alternative for patients across all risk spectrums to surgical aortic valve replacement. In these seminal trials, risk stratification was based on the Society of Thoracic Surgeons (STS) Predicted Risk of Mortality score. Derived from the surgical population, its generalizability to the TAVI population is questionable, , resulting in an emerging need for accurate risk stratification. The platelet-to-lymphocyte ratio (PLR) represents a novel, blood-based biomarker that can capture and simplify complex physiological processes, such as inflammation, into practical values that can be used by clinicians in their daily practice. An elevated PLR has been associated with a poorer prognosis in patients with acute coronary syndrome. Aortic stenosis has recently been characterized beyond its traditional wear-and-tear pathology as an active inflammatory process, similar to atherosclerosis, with matrix remodeling, valvular fibrosis, and eventual calcification. PLR integrates the detrimental effects of thrombocytosis (reflecting inflammation) and lymphopenia (a marker of physiological stress). , We hypothesized that elevated preprocedure PLR would be associated with an increased incidence of 30-day major adverse cardiovascular events (MACE) in patients following TAVI, consistent with 2 preliminary studies. ,
Methods
The study population was identified from the prospective single-center registry at The Alfred Hospital, Melbourne, Australia. Between August 2008, and January 2019, a total of 472 patients who underwent TAVI for severe symptomatic aortic stenosis were identified. Of the 472 patients identified, only 2 were excluded because of missing preprocedure blood results; the remaining 470 patients formed the study cohort. The study was approved by the local ethics committee (project number 300/20) and all patients provided written informed consent.
The Alfred Hospital TAVI registry prospectively recruits consecutive patients who undergo TAVI with either self-expanding or balloon-expandable valves. These valves were the CoreValve and Evolut R (Medtronic Inc., Minneapolis, Minnesota), Edwards Sapien XT and Sapien 3 (Edwards Lifesciences, Irvine, California), or Portico (Abbott, Chicago, Illinois) bioprostheses. Access was by way of the femoral, subclavian, apical, or direct aortic routes as determined by preprocedural computed tomography, angiography, and transthoracic and/or transesophageal echocardiography. All patients were reviewed by the multi-disciplinary heart team to decide on final suitability for TAVI.
PLR was computed as absolute platelet count divided by absolute lymphocyte count, calculated from the same blood sample obtained at a median of 1-day preprocedure. Aortic stenosis severity was assessed by transthoracic echocardiography: aortic valve area <1 cm 2 or aortic valve mean pressure gradient >40 mm Hg. Symptoms were graded using the New York Heart Association classification. Study end points were defined according to Valve Academic Research Consortium-2 criteria. Our primary outcome was MACE within 30 days of the index TAVI procedure (30-day MACE). MACE was defined as the combination of the following Valve Academic Research Consortium-2 variables: disabling stroke, nondisabling stroke, spontaneous acute myocardial infarction, and death.
The Shapiro-Wilk test was used to assess data for normality. Where data were not normally distributed, nonparametric tests were employed. For baseline data, the chi-square test was used for significance testing of categorical variables and the Kruskal-Wallis test for continuous variables. Categorical variables were expressed as number (%) and continuous variables as median (interquartile range). Univariate analysis was conducted using logistic regression. A multivariable logistic regression model of clinically significant variables, and variables that returned a p ≤0.10 from univariate analysis, was constructed. This purposeful selection modeling strategy has been established in the literature. The final multivariable model included: age, gender, self-expanding valve use, and procedural risk (STS score). All calculated p values were two-sided, and a threshold of p <0.05 was set for statistical significance. Statistical analysis was performed using the STATA Release 15.1 Statistical Software (StataCorp. 2017, College Station, Texas).
Results
A total of 470 patients who underwent TAVI at The Alfred Hospital were included in this study, of which 255 (54%) were men and the median age was 84 years. Within this cohort, 14 (3%) developed the primary outcome of 30-day MACE. Table 1 presents a comparison of the PLR quartile (Q) groups; Q1 (24.5 to 100), Q2 (100 to 133.4), Q3 (133.4 to 187.2), and Q4 (>187.2). Older patients were more likely to have a higher PLR (p = 0.019), whereas patients with diabetes mellitus were more likely to have a lower PLR (p = 0.040). The proportion of patients with cardiovascular risk factors, comorbidities, and procedural factors such as valve-type and access-site did not differ significantly between groups. The majority of patients underwent TAVI with a self-expanding device (73%) and transfemoral was the primary method of access (95%). Except for preprocedural severity of aortic regurgitation (p = 0.020), there were no significant preprocedural echocardiographic differences between groups.
| Quartile of platelet-to-lymphocyte ratio | ||||||
|---|---|---|---|---|---|---|
| Variable | Q1 (n=116) | Q2 (n=119) | Q3 (n=117) | Q4 (n=118) | Overall (n=470) | p-value |
| Age (years) | 83 (80-87) | 83 (81-86) | 85 (82-88) | 84 (80-87) | 84 (81-87) | 0.019 |
| Men | 62 (54%) | 67 (56%) | 58 (50%) | 68 (58%) | 255 (54%) | 0.61 |
| Hypertension | 93 (81%) | 79 (69%) | 80 (71%) | 83 (70%) | 335 (73%) | 0.16 |
| Diabetes mellitus | 42 (37%) | 40 (35%) | 24 (21%) | 31 (26%) | 137 (30%) | 0.040 |
| Atrial fibrillation | 33 (29%) | 44 (38%) | 37 (33%) | 47 (40%) | 161 (35%) | 0.27 |
| Cerebrovascular disease | 18 (16%) | 16 (13%) | 18 (15%) | 22 (19%) | 74 (16%) | 0.74 |
| Coronary artery disease | 55 (47%) | 56 (47%) | 54 (46%) | 62 (53%) | 227 (48%) | 0.76 |
| Peripheral vascular disease | 14 (12%) | 18 (16%) | 9 (8%) | 17 (15%) | 58 (13%) | 0.30 |
| NYHA class III/IV | 55 (48%) | 61 (54%) | 55 (49%) | 64 (55%) | 235 (51%) | 0.71 |
| Prior CABG | 22 (19%) | 21 (18%) | 19 (17%) | 23 (19%) | 85 (18%) | 0.96 |
| Prior balloon aortic valvuloplasty | 26 (25%) | 29 (27%) | 24 (23%) | 27 (27%) | 106 (25%) | 0.88 |
| Prior pacemaker implant | 11 (10%) | 11 (10%) | 9 (8%) | 13 (12%) | 44 (10%) | 0.83 |
| STS (%) | 3.3 (2.9-4.7) | 3.5 (2.5-5.6) | 3.9 (2.8-5.7) | 3.6 (2.8-6.2) | 3.5 (2.7-5.6) | 0.32 |
| Self-expanding valve | 80 (75%) | 76 (69%) | 79 (74%) | 75 (71%) | 310 (73%) | 0.74 |
| Trans-femoral access | 109 (94%) | 117 (98%) | 109 (94%) | 112 (95%) | 447 (95%) | 0.31 |
| Echocardiographic variables | ||||||
| MPG pre (mmHg) | 46 (38-54) | 46 (40-54) | 46 (40-56) | 46 (39-56) | 46 (39-54) | 0.95 |
| MPG 30 days (mmHg) | 10 (7-13) | 10 (7-13) | 10 (8-12) | 9 (8-12) | 10 (7-12) | 0.81 |
| AVA pre (cm 2 ) | 0.7 (0.6 – 0.8) | 0.7 (0.6 – 0.9) | 0.7 (0.6 – 0.9) | 0.7 (0.6 – 0.8) | 0.7 (0.6 -0.8) | 0.86 |
| AVA 30 days (cm 2 ) | 1.6 (1.4 – 1.9) | 1.7 (1.6 – 2.3) | 1.7 (1.5 – 2.0) | 1.8 (1.4 – 2.1) | 1.7 (1.5 -2.0) | 0.20 |
| AR pre (moderate/severe) | 8 (8%) | 4 (4%) | 5 (5%) | 17 (17%) | 34 (8%) | 0.020 |
| AR 30 days (moderate/severe) | 3 (4%) | 4 (5%) | 4 (5%) | 10 (14%) | 21 (7%) | 0.06 |
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