Current Insights and Novel Cardiovascular Magnetic Resonance-Based Techniques in the Prognosis of Non-Ischemic Dilated Cardiomyopathy.

Cardiac magnetic resonance (CMR) imaging has an important emerging role in the evaluation and management of patients with cardiomyopathies, especially in patients with dilated cardiomyopathy (DCM). It allows a non-invasive characterization of myocardial tissue, thus assisting early diagnosis and precise phenotyping of the different cardiomyopathies, which is an essential step for early and individualized treatment of patients. Using imaging techniques such as late gadolinium enhancement (LGE), standard and advanced quantification as well as quantitative mapping parameters, CMR-based tissue characterization is useful in the differential diagnosis of DCM and risk stratification. The purpose of this article is to review the utility of CMR in the diagnosis and management of idiopathic DCM, as well as risk prediction and prognosis based on standard and emerging CMR contrast and non-contrast techniques. This is consistent with current evidence and guidance moving beyond traditional prognostic markers such as ejection fraction.

Blockchain technology in Cardiovascular Medicine: a glance to the future? Results from a social media survey and future perspectives.

The leverage of digital facilities in medicine for disease diagnosis, monitoring, and medical history recording has become increasingly pivotal. However, the advancement of these technologies poses a significant challenge regarding data privacy, given the highly sensitive nature of medical information. In this context, the application of Blockchain technology, a digital system where information is stored in blocks and each block is linked to the one before, has the potential to enhance existing technologies through its exceptional security and transparency. This paradigm is of particular importance in cardiovascular medicine, where the prevalence of chronic conditions leads to the need for secure remote monitoring, secure data storage and secure medical history updating. Indeed, digital support for chronic cardiovascular pathologies is getting more and more crucial. This paper lays its rationale in three primary aims: 1) to scrutinize the existing literature for tangible applications of blockchain technology in the field of cardiology; 2) to report results from a survey aimed at gauging the reception of blockchain technology within the cardiovascular community, conducted on social media; 3) to conceptualize a web application tailored specifically to cardiovascular care based on blockchain technology. We believe that Blockchain technology may contribute to a breakthrough in healthcare digitalization, especially in the field of cardiology; in this context, we hope that the present work may be inspiring for physicians and healthcare stakeholders.

Myocardial Work Assessment in Patients after Coronary Artery Bypass Grafting during Cardiac Rehabilitation.

BACKGROUND: Myocardial work is an innovative echocardiographic tool to assess left ventricular performance. Emerging data have shown the added value of this method for evaluating cardiac function compared to traditional echocardiographic parameters and global longitudinal strain. However, few studies are present in the literature about the role of myocardial work during cardiac rehabilitation. Our aim was to assess the impact of a rehabilitation program on myocardial work indices in patients with preserved left ventricular ejection fraction and after coronary artery bypass grafting. In addition, we assessed the correlation between baseline myocardial work indices and their change after cardiac rehabilitation, establishing an optimal cut-off value to predict the improvement. METHODS: An observational, single-center, and prospective study was conducted. We enrolled patients referred to cardiac rehabilitation after coronary artery bypass grafting and with preserved left ventricular ejection fraction. Before and after the cardiac rehabilitation program, a comprehensive patient assessment was performed, including traditional transthoracic echocardiography, myocardial work analysis, and a six-minute walk test. RESULTS: Eighty-four patients were enrolled; the mean age was 67.96 (±7.42) years and 78.6% were male. The left ventricular ejection fraction was preserved in all patients, and the global longitudinal strain was -16.18 ± 2.55%, the global work index was 1588.56 ± 345 mmHg%, the global constructive work was 1771.27 ± 366.36 mmHg%, the global wasted work was 105.8 ± 72.02 mmHg%, and the global work efficiency was 92.63 ± 3.9% at baseline. After the cardiac rehabilitation program, the global work index, the global constructive work, and the six-minute walk test improved significantly (1588.56 ± 345 vs. 1960.2 ± 377.03 mmHg%, p-value < 0.001; 1771.27 ± 366.36 vs. 2172.01 ± 418.73 mmHg%, p-value < 0.001; 70.71 ± 40.2 vs. 437.5 ± 108.70 m, p-value < 0.001, respectively). CONCLUSIONS: Myocardial work indices, specifically global work index and global constructive work, improve after cardiac rehabilitation program in patients undergoing coronary artery bypass grafting with preserved left ventricular ejection fraction.

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions.

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.

Cost-effectiveness and diagnostic accuracy of focused cardiac ultrasound in the pre-participation screening of athletes: the SPORT-FoCUS study.

AIMS: The role of pre-participation screening (PPS) modalities in preventing sudden cardiac death (SCD) in athletes is debated due to a high false-positive rate. Focused cardiac ultrasound (FoCUS) has shown higher sensitivity and specificity, but its cost-effectiveness remains uncertain. This study aimed to determine the diagnostic performance and cost-effectiveness of FoCUS use in PPS. METHODS AND RESULTS: A total of 2111 athletes (77.4% male, mean age 24.9 ± 15.2years) underwent standardized family and medical history collection, physical examination, resting electrocardiography (ECG), FoCUS (10 min/5 views protocol), comprehensive echocardiography and exercise stress test. We prospectively evaluated three PPS incremental models: Model A, standardized medical history and physical examination Model B, Model A plus resting and stress ECG and Model C, Model B plus FoCUS (10 min/5 views protocol). We determined their incremental diagnostic accuracy and cost-effectiveness ratio. A total of 30 athletes were diagnosed with a cardiac condition associated with SCD: 3 were identified by Model A, 14 by Model B, and 13 athletes by Model C. The introduction of FoCUS markedly increased the sensitivity of PPS, compared with Model A and Model B (sensitivity 94% vs. 19% vs. 58% specificity 93% vs. 93% vs. 92%). The total screening costs were as follows: Model A 35.64 euros, Model B 87.68 euros, and Model C 120.89 euros. Considering the sole conditions at risk of SCD, the incremental cost-effectiveness ratio was 135.62 euros for Model B and 114.31 for Model C. CONCLUSIONS: The implementation of FoCUS into the PPS allows to identify a significantly greater number of athletes at risk of SCD and markedly lowers the false negative rate. Furthermore, the incorporation of FoCUS into the screening process has shown to be cost-effective.

A significant electrocardiography false-positive rate makes pre-participation screening (PPS) for sudden cardiac death (SCD) in athletes controversial. Focused cardiac ultrasound (FoCUS) may increase sensitivity and specificity however, its cost-effectiveness is unknown. This study evaluates the diagnostic performance and cost-effectiveness of FoCUS in PPS. Incorporating a simplified echocardiographic exam called FoCUS into PPS resulted in higher diagnostic reliability, with a lower rate of false negatives and a higher number of athletes at risk for SCD identified.The integration of FoCUS into the screening process resulted to be cost-effective in our athletes' cohort.

[Management of patients with type 2 diabetes during cardiac prevention and rehabilitation. An expert opinion from the Italian Alliance for Cardiovascular Rehabilitation and Prevention (ITACARE-P)]. / La gestione del paziente con diabete di tipo 2 in Cardiologia Preventiva e Riabilitativa. Expert opinion della Italian Alliance for Cardiovascular Rehabilitation and Prevention (ITACARE-P).

Patients with diabetes, regardless of their cardiovascular disease and their index event, are more and more often referred to Cardiac Rehabilitation Units. These patients usually show high or very high cardiovascular risk, marked disability and poor quality of life. Furthermore, those with older age, frailty, and female sex have even more rehabilitative needs, thus requiring fine individualized approaches. Consequently, in order to identify their therapeutic goals, the glycemic target should be pursued together with the effective reduction of the global cardiovascular risk. Modern exercise protocols are based on the synergic effect of both aerobic and strength training of moderate and high effort intensities, in order to achieve improvements of cardiorespiratory fitness and glycemic values as well. Exercise training and nutritional intervention are strictly related during the rehabilitation program, thus promoting better lifestyle in the long term too. New antidiabetic drugs (such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists) should be included into a specific "patient journey" along with other core components of the rehabilitation program. Therefore, the active role of all allied professionals (namely nurses, physiotherapists, dietitians and psychologists) is essential to the success of the cardiometabolic team. Diabetes should be routinely included in the outcome evaluation of cardiac rehabilitation programs and in every follow-up plan through a successful crosstalk among cardiologists, diabetologists and patients.

Management of Coronary Artery Disease in Older Adults: Recent Advances and Gaps in Evidence.

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults.

An Overview of Sport Participation and Exercise Prescription in Mitral Valve Disease.

The incidence of heart valve disease (HVD) has been rising over the last few decades, mainly due to the increasing average age of the general population, and mitral valve (MV) disease is the second most prevalent HVD after calcific aortic stenosis, but MV disease is a heterogeneous group of different pathophysiological diseases. It is widely proven that regular physical activity reduces all-cause mortality rates, and exercise prescription is part of the medical recommendations for patients affected by cardiovascular diseases. However, changes in hemodynamic balance during physical exercise (including the increase in heart rate, preload, or afterload) could favor the progression of the MV disease and potentially trigger major cardiac events. In young patients with HVD, it is therefore important to define criteria for allowing competitive sport or exercise prescription, balancing the positive effects as well as the potential risks. This review focuses on mitral valve disease pathophysiology, diagnosis, risk stratification, exercise prescription, and competitive sport participation selection, and offers an overview of the principal mitral valve diseases with the aim of encouraging physicians to embody exercise in their daily practice when appropriate.

Emerging sodium-glucose cotransporter-2 inhibitor therapies for managing heart failure in patients with chronic kidney disease.

INTRODUCTION: Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have risen in popularity for managing heart failure (HF) and chronic kidney disease (CKD), little guidance is available for the management of patients with an overlap of HF and CKD. AREAS COVERED: Following a brief review of the cardiorenal effects of SGLT2 inhibitors, this narrative review focused on the published clinical evidence pertaining to the cardiovascular and renal efficacy of SGLT2 inhibitors in patients with HF and CKD, including both randomized controlled trials and real-world observational studies. Real-world considerations of using SGLT2 inhibitors in these patients were also reviewed. EXPERT OPINION: Although no randomized controlled trial has specifically studied the use of SGLT2 inhibitors in patients with HF and CKD, evidence from existing trials is largely sufficient to demonstrate that SGLT2 inhibitors are efficacious in these patients, in whom these agents should be initiated early to maximally slow declines in renal function. Further studies should focus on better guiding the timing of initiating SGLT2 inhibitors, improving these agents' cost-effectiveness, and bettering equity of access to these agents. Further areas of study may include the prognostic implications of SGLT2 inhibitors-induced changes in biomarker levels (e.g. natriuretic peptides), and the potentials of SGLT1 inhibition.

Obesity and Cardiovascular Risk: Systematic Intervention Is the Key for Prevention.

Obesity is a serious public health issue and associated with an increased risk of cardiovascular disease events and mortality. The risk of cardiovascular complications is directly related to excess body fat mass and ectopic fat deposition, but also other obesity-related complications such as pre-type 2 diabetes, obstructive sleep apnoea, and non-alcoholic fatty liver diseases. Body mass index and waist circumference are used to classify a patient as overweight or obese and to stratify cardiovascular risk. Physical activity and diet, despite being key points in preventing adverse events and reducing cardiovascular risk, are not always successful strategies. Pharmacological treatments for weight reduction are promising strategies, but are restricted by possible safety issues and cost. Nonetheless, these treatments are associated with improvements in cardiovascular risk factors, and studies are ongoing to better evaluate cardiovascular outcomes. Bariatric surgery is effective in reducing the incidence of death and cardiovascular events such as myocardial infarction and stroke. Cardiac rehabilitation programs in obese patients improve cardiovascular disease risk factors, quality of life, and exercise capacity. The aim of this review was to critically analyze the current role and future aspects of lifestyle changes, medical and surgical treatments, and cardiac rehabilitation in obese patients, to reduce cardiovascular disease risk and mortality, and to highlight the need for a multidisciplinary approach to improving cardiovascular outcomes.

[Degenerative aortic valve stenosis: looking for a pharmacological prevention]. / Stenosi valvolare aortica degenerativa: alla ricerca di una prevenzione farmacologica.

Degenerative calcific aortic valve stenosis (CAVS) is a chronic disease whose prevalence has increased over the last decade because of the aging of the general population. CAVS pathogenesis is characterized by complex molecular and cellular mechanisms that promote valve fibro-calcific remodeling. During the first phase, referred to as initiation, the valve undergoes collagen deposition and lipid and immune cell infiltration due to mechanical stress. Subsequently, during the progression phase, the aortic valve undergoes chronic remodeling through osteogenic and myofibroblastic differentiation of interstitial cells and matrix calcification. Knowledge of the mechanisms underlying CAVS development supports the resort to potential therapeutic strategies that interfere with fibro-calcific progression. Currently, no medical therapy has demonstrated the ability to significantly prevent CAVS development or slow its progression. The only treatment available in symptomatic severe stenosis is surgical or percutaneous aortic valve replacement. The aim of this review is to highlight the pathophysiological mechanisms involved in CAVS pathogenesis and progression and to discuss potential pharmacological treatments able to inhibit the main pathophysiological mechanisms of CAVS, including lipid-lowering treatment with lipoprotein(a) as emergent therapeutic target.

The Role of Multimodality Imaging Approach in Acute Aortic Syndromes: Diagnosis, Complications, and Clinical Management.

Acute aortic syndromes are life-threatening conditions with high morbidity and mortality. The principal pathological feature is acute wall damage with possible evolution towards aortic rupture. Accurate and timely diagnosis is mandatory to avoid catastrophic consequences. Indeed, misdiagnosis with other conditions mimicking acute aortic syndromes is associated with premature death. In this view, cardiovascular imaging is necessary for the correct diagnosis and management. Echocardiography, computed tomography, magnetic resonance imaging, and aortography allow for diagnosis, guarantee immediate treatment, and detect associated complications. Multimodality imaging is essential in the diagnostic work-up to confirm or rule out acute aortic syndromes. The aim of this review is to highlight the contemporary evidence on the role of single cardiovascular imaging techniques and multimodality imaging in the diagnosis and management of acute aortic syndromes.

The Contemporary Role of Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging in the Diagnosis and Management of Pericardial Diseases.

Pericardial syndromes encompass different clinical conditions from acute pericarditis to idiopathic chronic pericardial effusion. Transthoracic echocardiography is the first and most important initial diagnostic imaging modality in most patients affected by pericardial disease. However, cardiac computed tomography (CCT) and cardiac magnetic resonance imaging (CMR) have recently gained a pivotal role in cardiology, and recent reports have supported the role of both of these advanced techniques in the evaluation and guiding therapy of pericardial disease. Most promising is the capability of CMR to identify the presence of pericardial inflammation, carrying both diagnostic and prognostic value in the setting of recurrent and chronic pericarditis. In addition, CCT permits accurate evaluation of the presence and extension of pericardial calcification, providing important information in confirming the diagnosis of constrictive pericarditis and during the preprocedural planning for patients undergoing pericardiectomy. Both CCT and CMR require specific expertise, especially for the evaluation of pericardial disease. The aim of the present review is to provide physicians an updated overview of CCT and CMR in pericardial disease, focusing on technical issues, recent research findings, and potential clinical applications.

Multimodality Cardiac Imaging in Young and Veteran Athletes: Updates on Atrial Function Assessment, Arrhythmia Predisposition and Pathology Discrimination.

Sports physicians and physiologists have aimed to assess exercise in young and master athletes so as to work out their conditioning levels and design training programs accordingly [...].

Electrocardiographic Features of Immune Checkpoint Inhibitor-Associated Myocarditis.

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events including myocarditis, whilst improving cancer-related outcomes. There is thus a clinical need to identify electrocardiographic manifestations of ICI-related myocarditis to guide clinical management. PubMed was searched for clinical studies and case reports describing electrocardiographic changes in patients with ICI-related myocarditis. A total of 6 clinical studies and 79 case reports were included. This revealed a range of presentations for patients on ICIs, including supraventricular arrhythmias, ventricular arrhythmias and heart block, and new changes of ST-T segment unrelated to coronary artery disease, ST-segment elevation or depression and T-wave abnormalities. Several patients showed low voltages in multiple leads and new onset Q-wave development. Patients with ICI-related myocarditis may develop new arrhythmia and ST-T changes, and infrequently low voltages in multiple leads.

[Cardiology as seen through social media]. / La cardiologia vista attraverso i social media.

The use of social media (SoMe) has spread worldwide among doctors, scientific societies, and researchers. SoMe offer a powerful platform to accelerate or create new contacts, spread scientific news, and increase visibility. A social media promotion strategy for cardiovascular medicine papers seems to be associated with increased online visibility and a higher number of citations. This effect is independent of the type of article and the total number of followers of the authors. Indeed, SoMe are democratic and even non-senior researchers may be popular on Twitter: your title is not as important as what you do on Twitter. Nevertheless, some physicians may be over-celebrated due to their presence on SoMe. This is why a new author index, the K-index, has been proposed. The K-index correlates the citations of a scientist with the number of Twitter followers. Even scientific journals and societies have recognized the importance of SoMe and in the last years they have appeared on SoMe with official accounts. Therefore, besides the classic impact factor, publishers now pay more and more attention to other parameters, such as the Altmetric score, which takes into account the number of citations, but also the number of downloads, mentions on SoMe, newspapers and tv news, web sites, and blogs. The COVID-19 pandemic has boosted the importance of SoMe for scientific content distribution, particularly for congresses. For all these reasons, it is important to understand the pros and cons of SoMe. It is also possible that SoMe will become a new education medium for continuing medical education.

Aortic regurgitation: A multimodality approach.

Aortic regurgitation (AR) is a common valvular pathology. Multimodality noninvasive cardiovascular imaging is routinely used to assess the mechanism of AR, degree, and its hemodynamic impact on the cardiovascular system. Collecting this information is crucial in establishing the prognosis and in guiding patient management and follow-up. While echocardiography remains the primary test to assess AR, a comprehensive assessment of this valvulopathy can be obtained by combining the information from different techniques. This state-of-the-art review is intended to provide an update ed overview of the applications, strengths, and limits of transthoracic echocardiography, cardiac magnetic resonance, and cardiac computed tomography in patients with AR.

Multimodality Imaging of the Neglected Valve: Role of Echocardiography, Cardiac Magnetic Resonance and Cardiac Computed Tomography in Pulmonary Stenosis and Regurgitation.

The pulmonary valve (PV) is the least imaged among the heart valves. However, pulmonary regurgitation (PR) and pulmonary stenosis (PS) can occur in a variety of patients ranging from fetuses, newborns (e.g., tetralogy of Fallot) to adults (e.g., endocarditis, carcinoid syndrome, complications of operated tetralogy of Fallot). Due to their complexity, PR and PS are studied using multimodality imaging to assess their mechanism, severity, and hemodynamic consequences. Multimodality imaging is crucial to plan the correct management and to follow up patients with pulmonary valvulopathy. Echocardiography remains the first line methodology to assess patients with PR and PS, but the information obtained with this technique are often integrated with cardiac magnetic resonance (CMR) and computed tomography (CT). This state-of-the-art review aims to provide an updated overview of the usefulness, strengths, and limits of multimodality imaging in patients with PR and PS.

Lipoprotein(a): a risk factor for atherosclerosis and an emerging therapeutic target.

Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease (ASCVD) and as a possible therapeutic target. Lp(a) atherogenic effects are attributed to several potential mechanisms in addition to cholesterol accumulation in the arterial wall, including proinflammatory effects mainly mediated by oxidised phospholipids. Several studies have found a causal and independent relationship between Lp(a) levels and cardiovascular risk. Furthermore, several studies also suggest a causal association between Lp(a) levels and calcific aortic valve stenosis. Available lipid-lowering agents have at best moderate impact on Lp(a) levels. Among available therapies, antibody proprotein convertase subtilisin/kexin type 9 inhibitors are the most effective in reducing Lp(a). Potent Lp(a)-lowering treatments that target LPA expression are under development. Lp(a) level measurement poses some challenges due to the absence of a definitive reference method and the reporting of Lp(a) values as molar (nanomoles per litre (nmol/L)) or mass concentrations (milligrams per decilitre (mg/dL)) by different assays. Currently, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, that is, in individuals with a family history of premature ASCVD, in patients with ASCVD not explained by standard risk factors or in those with recurrent events despite optimal management of traditional risk factors. Patients with high Lp(a) levels should be managed with more intensive approaches to treat other modifiable cardiovascular risk factors. Overall, this review focuses on Lp(a) as an ASCVD risk factor and therapeutic target. Furthermore, it reports practical recommendations for Lp(a) measurement and interpretation and updated evidence on Lp(a)-lowering approaches.