Anemia: Another Stone in the Wall of Takotsubo Outcomes?

Abstract

Takotsubo syndrome (TS) is an acute reversible clinical condition, characterized by transient left ventricular systolic dysfunction in the absence of significant coronary artery disease, especially occurring in women aged between 60 and 70 years. In the United States, TS is estimated to represent approximately 1% to 3% of all and 5% to 6% of female patients presenting with suspected acute coronary syndrome (ACS), and accounts for 0.02% of hospital admissions. Until a few years ago, common opinion was that patients with TS had generally a good short-term prognosis, with a rapid and complete improvement of left ventricle function. However, evidence revealed that the prognosis of TS should be reconsidered, case by case, depending on the presence of comorbidities and gender. Recently, anemia and iron deficiency (ID) have emerged as important negative factors for outcome of cardiovascular diseases, in particular for heart failure (HF). Anemia is defined by World Health Organization as hemoglobin (Hb) <13.0 g/dL in male adults and <12.0 g/dL in female adults, and ID is defined as ferritin levels below 100 mg/L or 100 to 299 mg/L with transferrin saturation of <20%. Anemia and ID are commonly reported in all HF forms, both with reduced ejection fraction and preserved ejection fraction. Anemia and ID have an estimated incidence ranging between 30% and 50% and are responsible of a series of negative outcomes, for example, reduced exercise tolerance, impaired quality of life, and poor long-term prognosis. Data from the National Health and Nutrition Examination Survey 2017 to 2018 reported that the prevalence of anemia and ID in the population with HF was 12% and 48%, respectively. As for acute HF, the results from the Beijing Acute Heart Failure (AHF) Registry study showed that anemic patients had higher 1-year mortality (38% vs 27%, P < .0001) and 1-year all-cause events, including all-cause death and readmission, rates (63% vs 57%, P < .0001) compared with non-anemic patients. After adjusting for covariates, anemia was associated with the increase of 1-year mortality (hazard ratio [HR]: 1.28, 95% CI: 1.11-1.47; P 1⁄4 .0005) and 1-year events (HR: 1.14, 95% CI: 1.03-1.26; P 1⁄4 .0154). Less data are available on ACS. A systematic review and meta-analysis investigating anemia and mortality among patients with ACS (27 studies, 233 144 patients) reported that anemia was associated with an increased risk of crude (unadjusted) all-cause mortality and reinfarction (relative risk [RR]: 2.08 and 1.25, respectively, P < .0001). After adjustments, although attenuated, the association remained significant (HR: 1.49, P < .001). More recently, in a cohort of more than 1100 Korean patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention with drug-eluting stent during a 5-year clinical follow-up, patients with anemia showed a higher incidence of any MI) (HR: 2.10, 95% CI: 1.33-3.34, P 1⁄4 .001), total major adverse cardiac events (MACE; HR: 1.51, 95% CI: 1.18-1.93, P 1⁄4 .001) in the entire cohort, and any MI (HR: 2.14, 95% CI: 1.07-4.25, P 1⁄4 .027) and total MACE (HR: 1.43, 95% CI: 1.01-2.01, P 1⁄4 .042) in the matched (anemia vs no anemia) cohort. In this issue of Angiology, Lu et al assessed the effect of anemia in a sample of 4733 patients hospitalized with a primary diagnosis of TS, from the National Inpatient Sample database (United States) 2016 to 2018. They found that patients with TS with anemia had significantly higher rates of in-hospital complications, including cardiogenic shock (11.4% vs 4.0%, P < .001), ventricular arrhythmia (6.6% vs 3.6%, P 1⁄4 .008), acute kidney injury (22.7% vs 13.1%, P < .001), acute respiratory failure (22.6% vs 13.1%, P < .001), and longer length of hospital stay (5.6 + 5.8 vs 3.6 + 3.6 days, P < .001). This represents novel and interesting information, since it provides an immediate picture of in-hospital complications. Previous data from the US Nationwide Readmission Database showed that patients with TS were likely to exhibit early hospital readmissions, just within the first month after discharge, and causes of readmissions were mostly cardiac, respiratory, and infective complications. However, on multivariate analysis, anemia was one of the significant predictors of readmission, together with age, cancer, and severe chronic comorbidities, such as diabetes, HF, chronic pulmonary disease, and peripheral vascular disease. On the other hand,