Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

Incidence of long-term cardiotoxicity and evolution of the systolic function in patients with breast cancer treated with anthracyclines.

BACKGROUND: Anthracycline cardiotoxicity (AC) may manifest years after treatment (long-term cardiotoxicity). There is little data on the incidence and natural history of AC in the current context, with protocols including lower anthracycline doses. The present study prospectively evaluated the incidence, time of occurrence and clinical correlates of long-term cardiotoxicity and the evolution of systolic function in patients with breast cancer treated with anthracyclines. METHODS: This study prospectively included 85 consecutive patients undergoing chemotherapy (CHT) with anthracyclines without trastuzumab. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years subsequent to the beginning of CHT. Clinical data and echocardiographic parameters were evaluated in all examinations. RESULTS: The mean dose of doxorubicin used was 243.53 mg/m2. Median follow-up of the current cohort was 4.5 years. At 1 year the incidence of AC was 1% and at the end of the follow-up 16.5% (14 of 85 patients). Therefore, the incidence of late cardiotoxicity (after the first year) was 15%. Of these 14 patients with AC, 12 had asymptomatic systolic dysfunction, 1 had heart failure and 1 suffered sudden death. Fifteen percent developed systolic dysfunction during follow-up. An early decline in strain was observed in patients who developed long-term AC. CONCLUSIONS: The incidence of long-term cardiotoxicity in patients treated with low-cumulative dose of anthracyclines is high, 16.5% at 4.5 years. This was observed in almost all cases after the first year of follow-up. Therefore, long-term monitoring may be advisable.

Cardiovascular risk factors during cancer treatment. Prevalence and prognostic relevance: insights from the CARDIOTOX registry.

AIMS: The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. METHODS AND RESULTS: A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality [hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4)]. CONCLUSIONS: This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.

Stratification and management of cardiovascular risk in cancer patients. A consensus document of the SEC, FEC, SEOM, SEOR, SEHH, SEMG, AEEMT, AEEC, and AECC.

Both cancer treatment and survival have significantly improved, but these advances have highlighted the deleterious effects of vascular complications associated with anticancer therapy. This consensus document aims to provide a coordinated, multidisciplinary and practical approach to the stratification, monitoring and treatment of cardiovascular risk in cancer patients. The document is promoted by the Working Group on Cardio Oncology of the Spanish Society of Cardiology (SEC) and was drafted in collaboration with experts from distinct areas of expertise of the SEC and the Spanish Society of Hematology and Hemotherapy (SEHH), the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Radiation Oncology (SEOR), the Spanish Society of General and Family Physicians (SEMG), the Spanish Association of Specialists in Occupational Medicine (AEEMT), the Spanish Association of Cardiovascular Nursing (AEEC), the Spanish Heart Foundation (FEC), and the Spanish Cancer Association (AECC).

Abnormal Electrocardiographic Findings in the Population Older Than 40 Years. Prevalence and Clinical Significance. Results of the OFRECE Study.

INTRODUCTION AND OBJECTIVES: Abnormal electrocardiographic findings are highly common. The aim of this study was to analyze the prevalence of abnormal electrocardiographic patterns in the general Spanish population aged 40 years or older. METHODS: This subanalysis of the OFRECE study selected a representative sample of the Spanish population aged 40 years or older. Clinical data and electrocardiograms were available in all participants. The electrocardiograms were read centrally. Each electrocardiogram was independently assessed by 2 trained cardiologists and, if there was disagreement, a third was consulted to reach a consensus-based diagnosis. Prior to reading the electrocardiograms, diagnostic criteria were strictly defined for each of the abnormalities analyzed. We analyzed the prevalence and clinical factors associated with cavity enlargement, conduction disorders, repolarization abnormalities, pathological Q waves, atrial and ventricular premature beats, and pre-excitation. RESULTS: A total of 8343 individuals were evaluated, (mean age, 59.2 years; 52.4% women). Only 4074 (51.2%) participants had a completely normal electrocardiogram. The most frequent abnormalities were nonspecific repolarization abnormalities (16%) associated with coronary heart disease and atrial fibrillation; right bundle-branch block (8.1%) associated with chronic pulmonary obstructive disease; left anterior hemiblock (6.5%) related to hypertension and congestive heart failure; and long PR interval (3.7%), which was associated with coronary heart disease. CONCLUSIONS: Electrocardiographic abnormalities are very common in the general population aged 40 years or older. Only about half of the population had a completely normal electrocardiogram.

Prevalence of Electrocardiographic Patterns Associated With Sudden Cardiac Death in the Spanish Population Aged 40 Years or Older. Results of the OFRECE Study.

INTRODUCTION AND OBJECTIVES: Some electrocardiographic patterns are associated with an increased risk of sudden cardiac death due to ventricular arrhythmias. There is no information on the prevalence of these patterns in the general population in Spain. The objective of this study was to analyze the prevalence of these patterns and associated clinical and epidemiological factors. METHODS: This subanalysis of the OFRECE study selected a representative sample of the Spanish population aged ≥ 40 years. We studied the presence or absence of electrocardiographic patterns of Brugada syndrome and QT interval abnormalities. Clinical data and electrocardiograms were available in all participants. Electrocardiograms were evaluated by 2 cardiologists and a third cardiologist was consulted if there was disagreement in the diagnosis. We calculated the weighted prevalence and clinical factors associated with the presence of Brugada-type patterns or QT segment abnormalities. RESULTS: Overall, 8343 individuals were evaluated (59.2 years, 52.4% female). There were 12 Brugada cases (type 1, 2 cases; type 2, 10 cases; weighted prevalence, 0.13%). For corrected QT (QTc) analysis, we excluded participants with left bundle branch block or without sinus rhythm. Weighted prevalences were as follows: short QTc (< 340ms) 0.18%, borderline QTc (441-469ms) 8.33%, long QTc (≥ 470ms criterion) 1.01% and long QTc (≥ 480 criterion) 0.42%. CONCLUSIONS: A total of 0.6% to 1.1% of the Spanish population aged ≥ 40 years has an electrocardiographic pattern associated with a higher risk of sudden death (Brugada syndrome, long QT, or short QT).

Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

INTRODUCTION: Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. METHODS AND ANALYSIS: The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. PRIMARY OBJECTIVE: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). SECONDARY OBJECTIVES: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. ETHICS AND DISSEMINATION: This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings. TRIAL REGISTRATION NUMBER: NCT02548364; Pre-results.

[Coronary revascularization: clinical features and indications]. / Indicaciones de revascularización: aspectos clínicos.

Coronary artery revascularization is an established therapeutic intervention and is therefore included in all treatment guidelines for patients with coronary artery disease. Although the procedure has been available for more than 40 years, constant technical progress in surgical and percutaneous revascularization continues to bring the benefits of revascularization therapy to new groups of patients. Therefore the indications and limitations of this approach need to be reviewed and updated periodically. The aim of revascularization therapy is to improve the prognosis or symptoms and quality of life in patients with ischemic heart disease. The revascularization process comprises two aspects: 1) indication and selection of the revascularization procedure, and 2) performance of the procedure. Involvement of the clinical cardiologist in the first step is fundamental. Basing their decisions on clinical, functional and anatomical features, these professionals detect and select patients who would benefit, and also help to select the revascularization technique. In this Update article on revascularization we review, for stable ischemic heart disease and non-ST segment elevation acute coronary syndromes, the following: 1) the most relevant aspects to consider when evaluating the need for and the type of revascularization (age, sex, diabetes, renal function, electrocardiographic changes, ventricular function and quantification of functional relevance of coronary artery disease and viability of the acinetic areas); 2) indications for surgical or percutaneous intervention, and the choice of therapeutic strategy according to the latest clinical evidence and guidelines of scientific societies, and 3) currently available data on the controversy regarding choice of the revascularization procedure in patients with multivessel disease.

[Anti-beta 2-glycoprotein I antibodies and systemic lupus erythematosus]. / Anticuerpos anti-beta 2-glucoproteína I y lupus eritematoso sistémico.

BACKGROUND: We aimed to study the presence of anti-2-glycoprotein I antibodies (anti-2GPI) in patients with systemic lupus erythematosus (SLE) analyzing their relationship with anticardiolipin antibodies (aCL). PATIENTS AND METHOD: 63 patients with SLE and 54 healthy volunteers. Detection of anti-2GPI antibodies was performed by ELISA. RESULTS: 25 (40%) patients with SLE and 1 (2%) control had anti-2GPI antibodies (p < 0.001). 17 patients with aCL (43%) had anti-2GPI antibodies and 4 patients (20%) without aCL were found to have anti-2GPI antibodies (p < 0.05). There was an association between thrombosis and aCL. However, the association between thrombosis and anti-2GPI antibodies was not significant. CONCLUSIONS: Anti-2GPI antibodies are more frequent in SLE and they are more prevalent in patients with aCL. There is an association between thrombosis and aCL but no significant association between thrombosis and anti-2GPI antibodies.

Tuberculous peritonitis after treatment with adalimumab.

We present a case of tuberculous peritonitis in a woman with rheumatoid arthritis (RA), treated with adalimumab, and we review the association between anti-tumour necrosis factor (anti-TNF) therapy and tuberculosis. There have been only 2 case reports of peritoneal tuberculosis associated with anti-TNF and only 1 with adalimumab.