[Secondary prevention of cardiovascular diseases : targeting all the cardiovascular risk factors]. / Prévention secondaire des maladies cardiovasculaires : cibler l'ensemble des facteurs de risque.

This article focuses on the secondary prevention of cardiovascular (CV) diseases, namely the prevention of recurrence in subjects with a personal history of CV event, and the prevention of a first event in patients identified as at very high risk. For all these patients at very high risk, treatment is primarily based on the application of hygienic and dietary measures, including increasing the volume of physical activity, modifying the diet, and obtaining, if necessary, weight loss, as well as stopping smoking. This strategy has proven its benefits in terms of reducing morbidity and mortality. In addition, these patients must receive pharmacological treatment, whose the additional benefits are proven. The article details the pharmacological classes that are currently recommended, as well as the optimal management of CV risk factors and the therapeutic targets to be achieved.

Cet article s'intéresse à la prévention secondaire des maladies cardio-vasculaires (CV), c'est-à-dire la prévention de la récidive chez les sujets ayant une histoire personnelle d'événement CV, et la prévention d'un premier événement chez les patients identifiés comme à très haut risque. Pour tous ces patients à très haut risque, la prise en charge est, avant tout, basée sur l'application de mesures hygiéno-diététiques, incluant l'augmentation du volume d'activité physique, la modification du régime alimentaire et l'obtention si nécessaire d'une perte pondérale, ainsi que l'arrêt du tabac. Cette stratégie a prouvé ses bénéfices en termes de réduction de la morbidité et de la mortalité. En outre, ces patients doivent recevoir un traitement pharmacologique, dont les bénéfices additionnels sont prouvés. L'article détaille les classes pharmacologiques recommandées actuellement, ainsi que la prise en charge optimale des facteurs de risque CV et les cibles thérapeutiques à atteindre.

[Prevention of radiotherapy-related cardiotoxicity : benefits of a specialized cardio-oncologic assessment and follow-up]. / Prévention de la cardio-toxicité de la radiothérapie : apport de la prise en charge cardio-oncologique.

To accept the toxic side effects of any treatment, whether medical, surgical or radiotherapeutic, cannot be avoided but implies to evaluate them taking into account the severity and prognosis of the disease that is concerned. Screening, preventing and treatment of these side effects are an integral aspect of the treatment of cancers. We will here review the contribution of the cardio-oncology, a recently emerged medical specialty. Cardiac irradiation cannot be avoided when treating several cancers, most frequently left sided breast cancer. As soon as radiotherapy is considered, it is of prime importance to evaluate each patient's risk factors and to handle them. If technical progresses have led to the complete disappearance of acute side effects of radiotherapy, this is not true for the delayed ones that may occur many years after the irradiation. Hence the need for «red flags¼ and for a systematic follow-up. Cardiac complications of left breast irradiation concern all aspects of cardiology: diseases of cardiac rhythm, valvulopathies, heart failure, coronary and pericardial disorders.

Admettre les effets secondaires d'un traitement, qu'il soit médical, chirurgical ou radiothérapique, est inévitable, mais impose de les évaluer en intégrant la gravité de l'affection pour laquelle ils sont prescrits. Leur dépistage, leur prévention et leur prise en charge font partie intégrante du traitement d'un cancer. Dans cette revue, nous ferons la synthèse de l'apport à cette démarche d'une discipline récente, la cardio-oncologie. L'irradiation cardiaque est incontournable lors du traitement de plusieurs cancers au premier rang desquels le cancer du sein gauche. Dès qu'elle est envisagée, il est essentiel d'évaluer les facteurs de risque de chaque patient et d'organiser leur prise en charge éventuelle. En effet, si les progrès techniques ont permis la disparition des complications cardiaques aiguës de la radiothérapie, ce n'est encore pas le cas des complications différées qui peuvent survenir de nombreuses années après l'irradiation. D'où la nécessité de «drapeaux rouges¼ et d'un suivi régulier systématique. Ces complications, rarement isolées, concernent tous les aspects de la cardiologie : troubles du rythme, valvulopathies, insuffisance cardiaque, maladies coronaires et atteintes péricardiques.

[Cardio-oncology and cardio-obstetrics : crucial role of a multidisciplinary approach]. / Cardio-oncologie et cardio-obstétrique : importance d'une approche multidisciplinaire.

In this clinical case, we describe the cardio-oncological history and the complexity of the management of a patient presenting a breast cancer diasgnosed during pregnancy followed by a postpartum cardiomyopathy. A multidisciplinary approach is mandatory.

Dans ce cas clinique, nous décrivons l'histoire cardio-oncologique et la complexité de prise en charge d'une patiente présentant un cancer mammaire découvert lors d'une grossesse, puis, une cardiomyopathie du post-partum. Une approche multidisciplinaire s'avère indispensable.

Mild Cardiotoxicity and Continued Trastuzumab Treatment in the Context of HER2-Positive Breast Cancer.

Breast cancer is the leading cause of cancer death in women worldwide. Trastuzumab, the main HER2-targeted treatment, faces limitations due to potential cardiotoxicity. The management of patients with mild cardiotoxicity on trastuzumab remains uncertain, resulting in treatment discontinuation and negative oncological outcomes. This retrospective study analyzed 23 patients who experienced decreased left ventricular function during trastuzumab treatment. During the 18-month follow-up period, two patients (9%) had severe declines in function, leading to treatment cessation, and one patient (4%) developed heart failure symptoms. However, 21 patients showed mild, reversible myocardial dysfunction without significant differences in final ventricular function compared to a control group (58.4% vs. 61.7%, respectively; p = 0.059). The declines in function were most pronounced at nine months but improved at twelve and eighteen months. Various echocardiographic parameters changed significantly over time. As predictors of severe cardiotoxicity, we identified the following: LVEF before initial chemotherapy (p = 0.022), as well as baseline LVEF before treatment with trastuzumab (p = 0.007); initial left ventricular end systolic volume (p = 0.027); and the initial global longitudinal strain (p = 0.021) and initial velocity time integral in the left ventricular outflow track (p = 0.027). In conclusion, the continuation of trastuzumab should be considered for most patients with mild cardiotoxicity, with close cardiac monitoring and cardioprotective measures. However, identifying the patients at risk of developing severe cardiotoxicity is necessary. According to our data, the initial LVEF and GLS levels appear to be reliable predictors.

Recurrent cardiac intimal sarcoma misdiagnosed as a myxoma or malignant transformation of a cardiac myxoma?

Cardiac intimal sarcoma is extremely rare and aggressive primary malignant cardiac tumors. Here, we reported the case of a young man initially operated for a tumor of the left atrium, causing a dynamic obstruction of the mitral valve and (mis-)diagnosed as a myxoma at the histopathological analysis. Patient presented a local recurrence at 3 months and was reoperated. Pathology revealed this time the presence of an intimal sarcoma. Patient received adjuvant chemotherapy. Despite a good local control, the 1-year follow-up positron emission tomography scan revealed the presence of a metastasis in the left adrenal gland that was surgically resected. This article aims to highlight the risk of misdiagnosis in case of cardiac tumors, the hypothetical concept of malignant transformation of a cardiac myxoma, the aggressive course of the extremely rare cardiac intimal sarcoma, and the therapeutic modalities available to treat this pathology.

Screening Program of Abdominal Aortic Aneurysm.

In Europe, the prevalence of abdominal aortic aneurysms (AAAs) in the elderly population (≥65 year old) has declined in the past decades to <4%. Aneurysmal degeneration of the aorta is a serious and potentially life-threatening vascular disease. Abdominal aortic aneurysms typically develop subclinically and often only become symptomatic when complicated by impending rupture. Most AAAs are discovered incidentally while investigating for an unrelated pathology. Ruptured AAA is the tenth leading cause of death in Belgium (0.32% of all deaths in 2014). Health-care providers have emphasized the importance of early detection of AAA and elective repair when the rupture risk outweighs operative risk (usual diameter threshold of 55 mm). Routine AAA screening programs, consisting of a single abdominal ultrasonography at the age of 65 years, aim to reduce the number of AAA-related deaths. Does population-based ultrasound screening for AAA achieve its objective and is it cost-effective? This literature review tries to answer these challenging questions.

Cardio-Oncology Services: rationale, organization, and implementation.

AIMS: Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer. METHODS AND RESULTS: The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy. CONCLUSION: The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.

Treating cardiovascular complications of radiotherapy: a role for new pharmacotherapies.

INTRODUCTION: Available data indicate that survivors of breast cancer and Hodgkin lymphoma who received mediastinal radiotherapy are at increased risk of developing radiation-induced cardiovascular diseases (RICVD) one or two decades after treatment. Although the risk with modern radiation treatment is likely to be lower in these patient groups, cardiotoxicity is still observed in a subset of patients. In addition, radiation-associated cardiovascular complications can, in the future, extend to other groups of cancer patients who are treated for tumors that are localized near the heart. AREAS COVERED: The authors briefly describe the most commonly observed types of RICVD. They then present an overview of preclinical animal and cellular models that have been used to investigate the mechanisms underlying RICVD pathophysiology. The beneficial effects of available drugs, and potential targets for new molecules are also reported. EXPERT OPINION: There is a need to develop cardio-oncological programs and pharmacotherapies specifically targeting RICVD. Beyond statins, ACE inhibitors, anti-inflammatory and antioxidant agents, preclinical studies indicate that TGFß receptor I inhibitors, Sestrin2 inducers, recombinant neuregulin-1 and miR-21 inhibitors might represent novel promising strategies. In order to properly determine the optimal therapeutic index for these molecules, in vivo models combining cancer and RICVD should be envisioned.

Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients.

BACKGROUND: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF). METHODS: In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured. RESULTS: Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information. CONCLUSIONS: Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF.

Cardiac Imaging: Multimodality Advances and Surveillance Strategies in Detection of Cardiotoxicity.

Contemporary cancer management has increased the overall number of cancer survivors, but cardiotoxicity remains a subject of concern, which is a major cause of noncancer mortality among survivors. Among the potential cardiovascular complications, left ventricular (LV) systolic dysfunction is a poor prognostic factor. The importance of its early detection is based on the principle that the likelihood of response to heart failure (HF) treatment is temporally related to the initiation of HF treatment. For these reasons, cardiac monitoring is commonly applied in general practice, based on serial measurements of LV ejection fraction (LVEF); transthoracic echocardiography (TTE) is generally used. However, the LVEF, as a diagnostic and predictive parameter, has significant limitations, which calls for more effective multimodality imaging strategies. This approach requires further study, but there is increasing available data in the literature, encouraging the combination of multimodality imaging parameters and techniques for early cancer therapeutic-related cardiac dysfunction (CTRCD) detection.

Protocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology.

AIMS: European Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of breast cancer patients referred to imaging laboratories for routine surveillance, suspected, or confirmed anticancer drug-related cardiotoxicity (ADRC). After a pilot phase (1 year recruitment and 1 year follow-up), some changes have been made to the protocol (version 1.0) and electronic case report form. METHODS AND RESULTS: Main changes of the version 2.0 concerned exclusion criteria, registry duration, and clarification of the population characteristics. Breast cancer radiotherapy has been removed as an exclusion criterion, which involves now only history of a pre-chemotherapy left ventricular dysfunction. The period for long-term registry recruitment has been reduced (December 2017), but the target study population was extended to 3000 patients. The characteristics of the population are now better defined: patients seen in an imaging lab, which will include patients undergoing chemotherapy with associated targeted therapy or no targeted therapy, at increased risk of ADRC. In total, 1294 breast cancer patients have been enrolled, and 783 case report forms locked from October 2014 to November 2016. Of these, 481 (61.4%) were seen at first evaluation and 302 (38.6%) while on oncologic treatment with anticancer drugs. Fifty-two patients (17.2%) were not in targeted therapies, 191 (63.3%) were ongoing targeted therapy, and 59 (19.5%) had completed it. Twenty-three (2.9%) patients had a suspected diagnosis and 35 (4.5%) a confirmed diagnosis of ADRC. Arterial hypertension was the most prevalent cardiovascular risk factor (29.2%) followed by diabetes (6.1%). Previous history of heart failure accounted for 0.5%, whereas previous cardiac disease was identified in 6.3% of population. CONCLUSION: The changes of the original protocol of the COT Registry and first update allow a first glance to the panorama of cardiovascular characteristics of breast cancer patients enrolled.

New biomarkers for primary mitral regurgitation.

BACKGROUND: Mitral regurgitation is a frequent valvular heart disease affecting around 2.5 % of the population with prevalence directly related to aging. Degeneration of mitral valve is broadly considered as a passive ongoing pathophysiological process and little is known about its physiological deregulation. The purpose of this study was to highlight new biomarkers of mitral regurgitation in order to decipher the underlying pathological mechanism as well as to allow the diagnosis and the monitoring of the disease. RESULTS: Modulation of various blood proteins expression was examined in patients suffering from different grades of mitral regurgitation (mild, moderate and severe) compared to healthy controls. To this end, several routine clinical assays and the multi analyte profile technology targeting 184 proteins were used. High-density lipoprotein, apolipoprotein-A1, haptoglobin and haptoglobin-α2 chain levels significantly decreased proportionally to the degree of mitral regurgitation when compared to controls. High-density lipoprotein and apolipoprotein-A1 levels were associated with effective regurgitant orifice area and regurgitant volume. Apolipoprotein-A1 was an independent predictor of severe mitral regurgitation. Moreover, with ordinal logistic regression, apolipoprotein-A1 remained the only independent factor associated with mitral regurgitation. In addition, myxomatous mitral valves were studied by immunocytochemistry. We observed an increase of LC3, the marker of autophagy, in myxomatous mitral valves compared with healthy mitral valves. CONCLUSION: These potential biomarkers of mitral regurgitation highlighted different cellular processes that could be modified in myxomatous degenerescence: reverse cholesterol transport, antioxidant properties and autophagy.

Prognostic effect of long-axis left ventricular dysfunction and B-type natriuretic peptide levels in asymptomatic aortic stenosis.

In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms. We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events. We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging. B-type natriuretic peptide (BNP) was measured in all patients. During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement. On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012). Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events. In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters.

The blue man: an unusual happy end of a spontaneous rupture of a coronary artery.

We report the case of spontaneous rupture of a coronary artery. It was that of a 56-year-old man admitted for dyspnoea and anterior thoracic pain. The most striking feature on physical examination was the marked cyanosis of his face, upper part of the thorax and the upper limb. The patient was haemodynamically unstable with tachycardia and hypotension. Cardiac tamponade was confirmed by echocardiography and computed tomography of the thorax. The patient was transferred for surgery. Emergency sternotomy revealed pericardial bloody effusion and a continuous bleeding around the posterior interventricular artery. No other perioperative findings could explain the haemopericardium. Haemostasis was obtained by a suture of the bleeding coronary artery.