Physical exercise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise.

Arterial hypertension (AH) is one of the most common pathologic conditions and uncontrolled AH is a leading risk factor for cardiovascular disease and mortality. AH chronically causes myocardial and arterial remodelling with hemodynamic changes affecting the heart and other organs, with potentially irreversible consequences leading to poor outcomes. Therefore, a proper and early treatment of AH is crucial after the diagnosis. Beyond medical treatment, physical exercise also plays a therapeutic role in reducing blood pressure, given its potential effects on sympathetic tone, renin-angiotensin-aldosterone system, and endothelial function. International scientific societies recommend physical exercise among lifestyle modifications to treat AH in the first stages of the disease. Moreover, some studies have also shown its usefulness in addition to drugs to reduce blood pressure further. Therefore, an accurate, personalized exercise prescription is recommended to optimize the prevention and treatment of hypertension. On the other hand, uncontrolled AH in athletes requires proper risk stratification and careful evaluation to practice competitive sports safely. Moreover, the differential diagnosis between hypertensive heart disease and athlete's heart is sometimes challenging and requires a careful and comprehensive interpretation in order not to misinterpret the clinical findings. The present review aims to discuss the relationship between hypertensive heart disease and physical exercise, from diagnostic tools to prevention and treatment strategies.

Can Methamphetamine-Induced Cardiotoxicity be Ameliorated by Aerobic Training and Nutrition Bio-shield Superfood Supplementation in Rats After Withdrawal?

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1ß), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1ß, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1ß, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.

Relation between frailty and hypertension is partially mediated by physical activity among males and females in the Canadian Longitudinal Study on Aging.

Frailty reflects the heterogeneity in aging and may lead to the development of hypertension and heart disease, but the frailty-cardiovascular relationship and whether physical activity modifies this relationship in males and females are unclear. We tested whether higher frailty was positively associated with hypertension and heart disease in males and females and whether habitual movement mediated this relationship. The relationship between baseline frailty with follow-up hypertension and heart disease was investigated using the Canadian Longitudinal Study on Aging at 3-year follow-up data (males: n = 13,095; females: n = 13,601). Frailty at baseline was determined via a 73-item deficit-based index, activity at follow-up was determined via the Physical Activity Scale for the Elderly, and cardiovascular function was self-reported. Higher baseline frailty level was associated with a greater likelihood of hypertension and heart disease at follow-up, with covariate-adjusted odds ratios of 1.08-1.09 (all, P < 0.001) for a 0.01 increase in frailty index score. Among males and females, sitting time and strenuous physical activity were independently associated with hypertension, with these activity behaviors being partial mediators (except male-sitting time) for the frailty-hypertension relationship (explained 5-10% of relationship). The strength of this relationship was stronger among females. Only light-moderate activity partially mediated the relationship (∼6%) between frailty and heart disease in females, but no activity measure was a mediator for males. Higher frailty levels were associated with a greater incidence of hypertension and heart disease, and strategies that target increases in physical activity and reducing sitting may partially uncouple this relationship with hypertension, particularly among females.NEW & NOTEWORTHY Longitudinally, our study demonstrates that higher baseline frailty levels are associated with an increased risk of hypertension and heart disease in a large sample of Canadian males and females. Movement partially mediated this relationship, particularly among females.

Artificial Intelligence Interpretation of the Electrocardiogram: A State-of-the-Art Review.

PURPOSE OF REVIEW: Artificial intelligence (AI) is transforming electrocardiography (ECG) interpretation. AI diagnostics can reach beyond human capabilities, facilitate automated access to nuanced ECG interpretation, and expand the scope of cardiovascular screening in the population. AI can be applied to the standard 12-lead resting ECG and single-lead ECGs in external monitors, implantable devices, and direct-to-consumer smart devices. We summarize the current state of the literature on AI-ECG. RECENT FINDINGS: Rhythm classification was the first application of AI-ECG. Subsequently, AI-ECG models have been developed for screening structural heart disease including hypertrophic cardiomyopathy, cardiac amyloidosis, aortic stenosis, pulmonary hypertension, and left ventricular systolic dysfunction. Further, AI models can predict future events like development of systolic heart failure and atrial fibrillation. AI-ECG exhibits potential in acute cardiac events and non-cardiac applications, including acute pulmonary embolism, electrolyte abnormalities, monitoring drugs therapy, sleep apnea, and predicting all-cause mortality. Many AI models in the domain of cardiac monitors and smart watches have received Food and Drug Administration (FDA) clearance for rhythm classification, while others for identification of cardiac amyloidosis, pulmonary hypertension and left ventricular dysfunction have received breakthrough device designation. As AI-ECG models continue to be developed, in addition to regulatory oversight and monetization challenges, thoughtful clinical implementation to streamline workflows, avoiding information overload and overwhelming of healthcare systems with false positive results is necessary. Research to demonstrate and validate improvement in healthcare efficiency and improved patient outcomes would be required before widespread adoption of any AI-ECG model.

Inhibitory effect of microRNA-21 on pathways and mechanisms involved in cardiac fibrosis development.

Cardiac fibrosis is a pivotal cardiovascular disease (CVD) process and represents a notable health concern worldwide. While the complex mechanisms underlying CVD have been widely investigated, recent research has highlighted microRNA-21's (miR-21) role in cardiac fibrosis pathogenesis. In this narrative review, we explore the molecular interactions, focusing on the role of miR-21 in contributing to cardiac fibrosis. Various signaling pathways, such as the RAAS, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, besides dysregulation in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs cause cardiac fibrosis. Besides, miR-21 in growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition play crucial roles. miR-21 capacity regulatory function presents promising insights for cardiac fibrosis. Moreover, this review discusses numerous approaches to control miR-21 expression, including antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation, all novel methods of cardiac fibrosis inhibition. In summary, this narrative review aims to assess the molecular mechanisms of cardiac fibrosis and its essential miR-21 function.

Unraveling cardiac fibrosis: insights into microRNA-21's key role and promising approaches for controlCardiac fibrosis poses a significant global health threat and plays a central role in cardiovascular diseases. This examination delves into recent research revealing the participation of microRNA-21 (MiR-21) in the progression of cardiac fibrosis, providing insight into its critical function in this process. The investigation explores diverse molecular interactions, underscoring MiR-21's contribution to the development of cardiac fibrosis. Various signaling pathways, including the Renin-Angiotensin-Aldosterone System, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, coupled with disturbances in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs), contribute to cardiac fibrosis. MiR-21's influence on growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition further emphasizes its crucial role. What adds promise to MiR-21 is its capacity for regulation, providing potential insights into controlling cardiac fibrosis. The review also investigates various methods to modulate MiR-21 expression, such as antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation ­ innovative approaches showing potential in inhibiting cardiac fibrosis. In summary, this narrative review aims to dissect the complex molecular mechanisms behind cardiac fibrosis, explicitly emphasizing the indispensable role of MiR-21. By comprehending these mechanisms, researchers can lay the groundwork for inventive interventions and therapeutic strategies to hinder cardiac fibrosis, ultimately contributing to advancing cardiovascular health.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Role of Early Left Atrial Functional Decline in Predicting Cardiotoxicity in HER2 Positive Breast Cancer Patients Treated With Trastuzumab.

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.

Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis.

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Cardiac manifestations in inherited metabolic diseases.

Inherited metabolic diseases (IMD) are caused by the functional defect of an enzyme, of genetic origin, that provokes a blockage in a specific metabolic pathway. Individually, IMD are considered rare diseases, with an incidence of less than 1/100,000 births. The symptoms are usually multisystemic, but frequently include cardiac manifestations. Of these, the most common are cardiomyopathies, especially hypertrophic cardiomyopathy. In addition, they can cause dilated or restrictive cardiomyopathy and non-compacted cardiomyopathy of the left ventricle. Characteristic signs also include rhythm alterations (atrio-ventricular conduction disturbances, Wolff-Parkinson-White syndrome or ventricular arrhythmias), valvular pathology and ischaemic coronary pathologies. The aim of this study is to present a narrative review of the IMD that may produce cardiac involvement. We describe both the specific cardiac manifestations of each disease and the systemic symptoms that guide diagnosis.

Role of the Lymphatics in Cardiac Disease.

Cardiovascular diseases remain the largest cause of death worldwide with recent evidence increasingly attributing the development and progression of these diseases to an exacerbated inflammatory response. As a result, significant research is now focused on modifying the immune environment to prevent the disease progression. This in turn has highlighted the lymphatic system in the pathophysiology of cardiovascular diseases owing, in part, to its established function in immune cell surveillance and trafficking. In this review, we highlight the role of the cardiac lymphatic system and its potential as an immunomodulatory therapeutic target in selected cardiovascular diseases.

Evolving Role of Three-Dimensional Echocardiography for Right Ventricular Volume Analysis in Pediatric Heart Disease: Literature Review and Clinical Applications.

Accurate knowledge of right ventricular (RV) volumes and ejection fraction is fundamental to providing optimal care for pediatric patients with congenital and acquired heart disease, as well as pulmonary hypertension. Traditionally, these volumes have been measured using cardiac magnetic resonance because of its accuracy, reproducibility, and freedom from geometric assumptions. More recently, an increasing number of studies have described the measurement of RV volumes using three-dimensional (3D) echocardiography. In addition, volumes by 3D echocardiography have also been used for outcome research studies in congenital heart surgery. Importantly, 3D echocardiographic acquisitions can be obtained over a small number of cardiac cycles, do not require general anesthesia, and are less costly than CMR. The ease and safety of the 3D echocardiographic acquisitions allow serial studies in the same patient. Moreover, the studies can be performed in various locations, including the intensive care unit, catheterization laboratory, and general clinic. Because of these advantages, 3D echocardiography is ideal for serial evaluation of the same patient. Despite these potential advantages, 3D echocardiography has not become a standard practice in children with congenital and acquired heart conditions. In this report, the authors review the literature on the feasibility, reproducibility, and accuracy of 3D echocardiography in pediatric patients. In addition, the authors investigate the advantages and limitations of 3D echocardiography in RV quantification and offer a pathway for its potential to become a standard practice in the assessment, planning, and follow-up of congenital and acquired heart disease.

Cardiac evaluation in pregnant patients with dyspnea and palpitations.

BACKGROUND: Symptoms of underlying cardiac disease in pregnancy can often be mistaken for common complaints because of normal physiological changes in pregnancy. Echocardiographic evaluation of patients with symptoms of palpitations and dyspnea can detect structural changes and identify high-risk features. OBJECTIVE: This study aimed to examine transthoracic echocardiograms of perinatal individuals completed for palpitations or dyspnea to determine the frequency of identifying structural changes. STUDY DESIGN: This was a retrospective cohort study of all perinatal individuals with a transthoracic echocardiogram at a single academic center between October 1, 2017, and May 1, 2022. The indication for the echocardiogram, demographics, and clinical characteristics were recorded. Transthoracic echocardiograms with any abnormal findings noted in the transthoracic echocardiogram report were reviewed and categorized into findings of congenital heart disease, valvular disease, pericardial effusion, evidence of ischemia or wall motion abnormalities, abnormal diastolic or systolic function, and other. RESULTS: Of 539 transthoracic echocardiograms completed on 478 individuals who were pregnant or in the 12-week postpartum period, 96 (17.8%) had an indication of palpitations, and 32 (5.9%) had an indication of dyspnea. Abnormal findings were seen in 21.9% of patients with palpitations and in 34.4% of patients with dyspnea. In patients with palpitations who had abnormal findings, 33.3% had congenital heart disease; 33.3% had mild valvular disease, including mitral valve prolapse; 19.0% had a pericardial effusion; and 14.3% had evidence of ischemia or wall motion defects. Abnormal transthoracic echocardiogram findings in the dyspnea cohort included ischemia or wall motion defects (27.3%), mild valvular disease or mitral valve prolapse (36.4%), and abnormal systolic or diastolic function (36.4%). CONCLUSION: Many of the transthoracic echocardiograms completed for patients with dyspnea or palpitations identified no structural abnormality; however, in 1 of 3 to 1 of 4 patients, underlying structural heart disease was identified. Although some of these abnormalities were unlikely to change delivery plans, such as mild valvular disease or small effusions, other abnormalities, such as ischemia, congenital abnormalities, and abnormal systolic or diastolic function, were likely to have implications for pregnancy and postpartum management.

Sex-based differences in short- and longer-term diet-induced metabolic heart disease.

Sex-based differences in the development of obesity-induced cardiometabolic dysfunction are well documented, however, the specific mechanisms are not completely understood. Obesity has been linked to dysregulation of the epitranscriptome, but the role of N6-methyladenosine (m6A) RNA methylation has not been investigated in relation to the sex differences during obesity-induced cardiac dysfunction. In the current study, male and female C57BL/6J mice were subjected to short- and long-term high-fat/high-sucrose (HFHS) diet to induce obesogenic stress. Cardiac echocardiography showed males developed systolic and diastolic dysfunction after 4 mo of diet, but females maintained normal cardiac function despite both sexes being metabolically dysfunctional. Cardiac m6A machinery gene expression was differentially regulated by duration of HFHS diet in male, but not female mice, and left ventricular ejection fraction correlated with RNA machinery gene levels in a sex- and age-dependent manner. RNA-sequencing of cardiac transcriptome revealed that females, but not males may undergo protective cardiac remodeling early in the course of obesogenic stress. Taken together, our study demonstrates for the first time that cardiac RNA methylation machinery genes are regulated early during obesogenic stress in a sex-dependent manner and may play a role in the sex differences observed in cardiometabolic dysfunction.NEW & NOTEWORTHY Sex differences in obesity-associated cardiomyopathy are well documented but incompletely understood. We show for the first time that RNA methylation machinery genes may be regulated in response to obesogenic diet in a sex- and age-dependent manner and levels may correspond to cardiac systolic function. Our cardiac RNA-seq analysis suggests female, but not male mice may be protected from cardiac dysfunction by a protective cardiac remodeling response early during obesogenic stress.

The future of CMR: All-in-one vs. real-time CMR (Part 2).

Cardiac Magnetic Resonance (CMR) protocols can be lengthy and complex, which has driven the research community to develop new technologies to make these protocols more efficient and patient-friendly. Two different approaches to improving CMR have been proposed, specifically "all-in-one" CMR, where several contrasts and/or motion states are acquired simultaneously, and "real-time" CMR, in which the examination is accelerated to avoid the need for breathholding and/or cardiac gating. The goal of this two-part manuscript is to describe these two different types of emerging rapid CMR protocols. To this end, the vision of all-in-one and real-time imaging are described, along with techniques which have been devised and tested along the pathway of clinical implementation. The pros and cons of the different methods are presented, and the remaining open needs of each are detailed. Part 1 tackles the "All-in-One" approaches, and Part 2 focuses on the "Real-Time" approaches along with an overall summary of these emerging methods.

Preclinical Models of Cardiac Disease: A Comprehensive Overview for Clinical Scientists.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.