World Heart Federation Cholesterol Roadmap: The Portuguese case.

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden.

Chest Computed Tomography for Lymphoma Staging: A Wasted Opportunity for Cardiovascular Risk Stratification?

AIM: Patients with a lymphoma diagnosis undergo non-gated chest computed tomography (CT) scans as part of cancer diagnosis or staging. Although coronary artery calcification (CAC) is traditionally evaluated on dedicated cardiac CT, CAC can also be detected on standard chest CT. This exploratory study aimed to determine the prognostic value of CAC detected on non-gated chest CT and to report its use on clinical practice. METHOD: Consecutive patients with a lymphoma diagnosis who performed non-contrasted non-gated chest CT for cancer diagnosis or staging were included and retrospectively evaluated. Coronary artery calcification was evaluated by quantitative (Agatston score) and qualitative (visual) assessment. RESULTS: Fifty-seven patients were included in this study (mean age 61±15 years; 58% male). Coronary artery calcification was identified in 22 patients (39%), most of them with multi-vessel involvement. Coronary artery calcification was qualitatively classified as mild, moderate and severe in 11%, 19% and 9% patients, respectively. This study suggested that moderate or severe CAC was an independent predictor of all-cause mortality (odds ratio 3, 95% confidence interval 2-11; p=0.04) after adjusting for cardiovascular risk factors and lymphoma staging. Regarding quantitative evaluation, a higher CAC score was also associated with higher mortality. While significant CAC was identified in 22 patients, it was only reported in four patients. CONCLUSIONS: The preliminary findings of this hypothesis-generating study support the investigation of CAC identified by chest CT for diagnosis/staging of cancer as a risk modifier in the global risk assessment of patients with lymphoma. The unrecognition and underreporting of this finding may represent a wasted opportunity to detect subclinical coronary atherosclerosis in these patients and may help in guiding preventive cardiology care.

Interventional cardiology in cancer patients: A position paper from the Portuguese Cardiovascular Intervention Association and the Portuguese Cardio-Oncology Study Group of the Portuguese Society of Cardiology.

The field of Cardio-Oncology has grown significantly, especially during the last decade. While awareness of cardiotoxicity due to cancer disease and/or therapies has greatly increased, much of the attention has focused on myocardial systolic disfunction and heart failure. However, coronary and structural heart disease are also a common issue in cancer patients and encompass the full spectrum of cardiotoxicity. While invasive percutaneous or surgical intervention, either is often needed or considered in cancer patients, limited evidence or guidelines are available for dealing with coronary or structural heart disease. The Society for Cardiovascular Angiography and Interventions consensus document published in 2016 is the most comprehensive document regarding this particular issue, but relevant evidence has emerged since, which render some of its considerations outdated. In addition to that, the recent 2022 ESC Guidelines on Cardio-Oncology only briefly discuss this topic. As a result, the Portuguese Association of Cardiovascular Intervention and the Cardio-Oncology Study Group of the Portuguese Society of Cardiology have partnered to produce a position paper to address the issue of cardiac intervention in cancer patients, focusing on percutaneous techniques. A brief review of available evidence is provided, followed by practical considerations. These are based both on the literature as well as accumulated experience with these types of patients, as the authors are either interventional cardiologists, cardiologists with experience in the field of Cardio-Oncology, or both.

Cardiovascular Health Metrics Differ Between Individuals With and Without Cancer.

BACKGROUND: Although individuals with cancer experience high rates of cardiovascular morbidity, there are limited data on the potential differences in cardiovascular health (CVH) metrics between individuals with and without cancer. METHODS AND RESULTS: The National Health and Nutrition Examination Survey between 2015 and 2020 was queried to evaluate the prevalence of health metrics that comprise the American Heart Association Life's Essential 8 construct of cardiovascular health among adult individuals with and without cancer in the United States. Health metric scores were also evaluated according to important patient demographics including age, sex, race and ethnicity, and socioeconomic status. Among 4370 participants representing >180 million US adults, 9.4% had a history of cancer. Individuals with cancer had lower overall cardiovascular health scores (67.1 versus 69.1, P<0.001) compared with individuals without cancer. Among individual components of the cardiovascular health score, those with cancer had better health scores on key behaviors including physical activity, diet, and sleep compared with those without cancer, although variation was noted based on age. Higher scores on these modifiable health behaviors among those with cancer compared with those without cancer were noted in older individuals, in White individuals compared with other races and ethnicities, and in individuals with higher socioeconomic status. CONCLUSIONS: We highlight important variations in simple cardiovascular health metrics among individuals with cancer compared with individuals without cancer and demonstrate differences among health metrics based on age, race and ethnicity, and socioeconomic status. These findings may explain ongoing racial, ethnic, and socioeconomic status disparities in the cancer population and provide a framework for optimizing cardiovascular health among individuals with cancer.

Clinical experience of a cardio-oncology consultation at a tertiary university hospital in Portugal: An observational study.

INTRODUCTION: Heart disease and cancer are the two leading causes of morbidity and mortality worldwide. Advances in cancer screening and management have led to longer survival and better quality of life. Despite this progress, many cancer patients experience cardiovascular complications during and after cancer treatment. This study describes the experience of a cardio-oncology program at tertiary academic hospital. METHODS: In this retrospective observational study, cancer patients referred to the CHULN cardio-oncology consultation (COC) between January 2016 and December of 2019 were included. Data collected included: patient demographics, cancer type, reason for referral, cardiovascular risk factors, cardiac and oncologic treatments and clinical outcomes. RESULTS: A total of 520 patients (mean age: 65 ± 14 years; 65% women) were referred to the COC. The main reasons for referral were suspected heart failure (26%), pre-high risk chemotherapy assessment (20%) and decreased LVEF (15%). Pre-existing cardiovascular risk factors were common (79%) and 309 (59%) were taking cardiac medications. The most common type of malignancy was breast cancer (216, 41%) followed by gastrointestinal (139, 27%). More than half received anthracycline-based regimens (303, 58%). Most patients (401; 77%) successfully completed cancer therapy. At the time of last data collection, the majority of patients were alive (430, 83%). Cardiac-related mortality was observed in 16%. CONCLUSIONS: The close collaboration between cardiology and oncology teams and timely cardiac monitoring was the key to the majority of patients to completing their prescribed cancer therapy.

Molecular Changes In Cardiac Tissue As A New Marker To Predict Cardiac Dysfunction Induced By Radiotherapy.

The contribution of radiotherapy, per se, to late cardiotoxicity remains controversial. To clarify its impact on the development of early cardiac dysfunction, we developed an experimental model in which the hearts of rats were exposed, in a fractionated plan, to clinically relevant doses of ionizing radiation for oncological patients that undergo thoracic radiotherapy. Rat hearts were exposed to daily doses of 0.04, 0.3, and 1.2 Gy for 23 days, achieving cumulative doses of 0.92, 6.9, and 27.6 Gy, respectively. We demonstrate that myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of >15% from baseline) in a dose-dependent manner at 18 months. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Before GLS impairment detection, several tools (qRT-PCR, mass spectrometry, and western blot) were used to assess molecular changes in the cardiac tissue. The number/expression of several genes, proteins, and KEGG pathways, related to inflammation, fibrosis, and cardiac muscle contraction, were differently expressed in the cardiac tissue according to the cumulative dose. Subclinical cardiac dysfunction occurs in a dose-dependent manner as detected by molecular changes in cardiac tissue, a predictor of the severity of global longitudinal strain impairment. Moreover, there was no dose threshold below which no myocardial deformation impairment was detected. Our findings i) contribute to developing new markers and exploring non-invasive magnetic resonance imaging to assess cardiac tissue changes as an early predictor of cardiac dysfunction; ii) should raise red flags, since there is no dose threshold below which no myocardial deformation impairment was detected and should be considered in radiation-based imaging and -guided therapeutic cardiac procedures; and iii) highlights the need for personalized clinical approaches.

Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY-HEART study).

Background: In the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose-response relationships between cardiac doses and these events. Methods: Within the frame of the MEDIRAD European project (2017-2022), the prospective multicenter EARLY-HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40-75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle-tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction >15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV). Results: The sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p <0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p <0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction. Conclusion: These results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.

Cost-effectiveness of cardio-oncology clinical assessment for prevention of chemotherapy-induced cardiotoxicity.

INTRODUCTION: Cancer chemotherapy increases the risk of heart failure. This cost-effectiveness study analyzes cardio-oncology imaging assessment of left ventricular ejection fraction (LVEF) using a Portuguese healthcare payer perspective and a five-year time horizon. METHODS: Two cardioprotective strategies were assessed: universal cardioprotection (UCP) for all patients and cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX). A Markov model, informed by the retrospective clinical course of breast cancer patients followed in a Portuguese public hospital, was developed to assess the cost-effectiveness of LVEF cardio-oncology imaging assessment. Data on transition probabilities, costs and utilities were retrieved from both the retrospective data and published literature to assess the cost-effectiveness of LVEF echocardiographic assessment. Costs and utilities of the cardioprotective strategies were assessed over a five-year range, using probabilistic sensitivity analyses. RESULTS: In the reference case of a 63-year-old breast cancer patient treated with cardioprotection initiated on diagnosis of EF-CTX, the five-year time horizon (4.22 QALYs and €2594 cost over five years) dominated UCP (3.42 QALYS and €3758 cost over five years). Under a time horizon of five years at a willingness-to-pay threshold of €22 986, over 65.7% of simulations provided additional QALYs. Monte Carlo simulation of the Markov model had no effect on the model's conclusions. CONCLUSION: In the Portuguese public healthcare system and under specific hypotheses, from a healthcare payer perspective, EF-CTX-guided cardioprotection for patients at risk of chemotherapy-related cardiotoxicity provides more QALYs at lower cost than UCP.

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats.

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional imaging to study the cardiac anatomy of the left ventricle and M-mode echo to assess its dimensions. However, this could limit a comprehensive study. Herein, we describe a protocol that allows an assessment of the heart chamber size, left ventricular function (systolic and diastolic) and valvular function. A conventional medical ultrasound machine was used in this protocol and different echo views were obtained through left parasternal, apical and suprasternal windows. In the left parasternal window, the long and short axis were acquired to analyze left chamber dimensions, right ventricle and pulmonary artery dimensions, and mitral, pulmonary and aortic valve function. The apical window allows the measurement of heart chamber dimensions and evaluation of systolic and diastolic parameters. It also allows Doppler assessment with detection and quantification of heart valve disturbances (regurgitation or stenosis). Different segments and walls of the left ventricle are visualized throughout all views. Finally, the ascending aorta, aortic arch, and descending aorta can be imaged through the suprasternal window. A combination of ultrasound imaging, Doppler flow and tissue Doppler assessment have been obtained to study cardiac morphology and function. This represents an important contribution to improve the assessment of cardiac function in adult rats with impact for research using these animal models.

Heart disease and pregnancy: State of the art. / Cardiopatia e gravidez ­ o estado da arte.

The association between heart disease and pregnancy is increasingly prevalent. Although most women with heart disease tolerate the physiological changes of pregnancy, there are heart conditions that manifest for the first time during pregnancy and others that totally contraindicate a pregnancy. It is therefore important to establish multidisciplinary teams dedicated to the management of women with heart disease who intend to become, or who already are, pregnant. The aim of this article is to systematically review current knowledge on the approach to women with high-risk cardiovascular disease during pregnancy.

circRNA-miRNA cross-talk in the transition from paroxysmal to permanent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in western countries. The factors governing the progression of AF to a permanent chronic condition are still not well characterized. Among epigenetic factors, non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs have been recently described as important players involved in the AF progression. We hypothesize about the existence of additional regulatory layers in AF involving an intricate cross-talk between different ncRNA species, namely miRNAs and circRNAs for the establishment of a chronic AF condition. METHODS AND RESULTS: We have performed an unbiased study analyzing the expression profile for miRNAs and circRNAs in left-atrial biopsies from patients with paroxysmal and permanent AF by RNA-seq. The transition from paroxysmal to permanent AF is characterized by a pattern of down-regulated miRNAs, concomitant to the appearance of specific circRNA species. The analysis of the sponging activities of the circRNAs exclusively expressed in permanent AF samples, allowed us to determine that they could be responsible for the downregulation of specific miRNAs in establishment of a permanent AF condition. CONCLUSION: Sponging activity of circRNAs sequestering specific miRNAs is an important factor to be considered for the determination of the molecular mechanisms involved in AF progression.

Improving Hypertension Outcome Measurement in Low- and Middle-Income Countries.

High blood pressure is the leading modifiable risk factor for mortality, accounting for nearly 1 in 5 deaths worldwide and 1 in 11 in low-income countries. Hypertension control remains a challenge, especially in low-resource settings. One approach to improvement is the prioritization of patient-centered care. However, consensus on the outcomes that matter most to patients is lacking. We aimed to define a standard set of patient-centered outcomes for evaluating hypertension management in low- and middle-income countries. The International Consortium for Health Outcomes Measurement convened a Working Group of 18 experts and patients representing 15 countries. We used a modified Delphi process to reach consensus on a set of outcomes, case-mix variables, and a timeline to guide data collection. Literature reviews, patient interviews, a patient validation survey, and an open review by hypertension experts informed the set. The set contains 18 clinical and patient-reported outcomes that reflect patient priorities and evidence-based hypertension management and case-mix variables to allow comparisons between providers. The domains included are hypertension control, cardiovascular complications, health-related quality of life, financial burden of care, medication burden, satisfaction with care, health literacy, and health behaviors. We present a core list of outcomes for evaluating hypertension care. They account for the unique challenges healthcare providers and patients face in low- and middle-income countries, yet are relevant to all settings. We believe that it is a vital step toward international benchmarking in hypertension care and, ultimately, value-based hypertension management.

Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort Study (MEDIRAD EARLY HEART Study).

BACKGROUND: Breast cancer is the most common cancer among women, and radiotherapy plays a major role in its treatment. However, breast cancer radiotherapy can lead to incidental irradiation of the heart, resulting in an increased risk for a variety of heart diseases arising many years after radiotherapy. Therefore, identifying breast cancer patients at the highest risk for radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention, which may contribute to healthy aging. There is still a need for precise knowledge on the relationship between radiation dose to specific cardiac structures and early subclinical cardiac changes and their occurrence over time that could finally lead to cardiac complications. OBJECTIVE: The MEDIRAD EARLY HEART study aims to identify and validate new cardiac imaging and circulating biomarkers of radiation-induced cardiovascular changes arising within first 2 years of breast cancer radiotherapy and to develop risk models integrating these biomarkers combined with precise dose metrics of cardiac structures based on three-dimensional dosimetry. METHODS: The EARLY HEART study is a multicenter, prospective cohort study in which 250 women treated for breast cancer and followed for 2 years after radiotherapy will be included. Women treated with radiotherapy without chemotherapy for a unilateral breast cancer and aged 40-75 years meet the inclusion criteria. Baseline and follow-up data include cardiac measurements based on two-dimensional speckle-tracking echocardiography, computed tomography coronary angiography, cardiac magnetic resonance imaging, and a wide panel of circulating biomarkers of cardiac injury. The absorbed dose will be evaluated globally for the heart and different substructures. Furthermore, the dose-response relationship will allow modeling the radiation-induced occurrence and evolution of subclinical cardiac lesions and biomarkers to develop prediction models. RESULTS: This study details the protocol of the MEDIRAD EARLY HEART study and presents the main limits and advantages of this international project. The inclusion of patients began in 2017. Preliminary results are expected to be published in 2019, and complete analysis should be published in 2021. CONCLUSIONS: The MEDIRAD EARLY HEART study will allow identifying the main cardiac imaging and blood-based determinants of radiation-induced cardiac injuries to better propose primary and secondary preventive measures in order to contribute to enhanced patient care and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03297346; https://clinicaltrials.gov/ct2/show/NCT03297346 (Archived by WebCite at http://www.webcitation.org/72KS7MIUU). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9906.

Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction.

BACKGROUND: MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: One hundred and forty-two consecutive STEMI patients treated with primary angioplasty were included in the study. Serum levels of miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p and -499a-5p were measured at the time of cardiac catheterization by quantitative polymerase chain reaction and related to in-hospital and long-term outcome. During a follow up of 20.8 months, 9 patients died, 6 had recurrence of myocardial infarction, and 26 patients suffered an adverse cardiovascular event. Event-free survival was significantly worse in patients with a higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events. CONCLUSIONS: This study showed that the miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. (Circ J 2016; 80: 2183-2191).