Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions. The evolving landscape of cancer treatment has brought about significant advancements, allowing for improved patient survival rates. However, the cardiovascular impact of many cancer therapies is now better understood and has been associated with a range of cardiotoxic effects, highlighting the pressing need for effective monitoring and management ,2,3,4.Despite the existence of several international guidelines and position papers regarding the cardiovascular monitoring and management of cancer drug recipients, their limited empirical basis makes it challenging to determine a practical approach suitable for every clinical scenario ,6,7,8,9.This article delves deep into the complex interplay between cancer therapy and the cardiovascular system, emphasizing the value of a state-of-the-art multimodality imaging approach to stratify the patient’s risk before starting cancer therapy, identify early cardiovascular injury during treatment and detect cardiovascular injury in long-term.Beginning with a detailed exploration of the newly introduced terminology from the 2022 European Society of Cardiology (ESC) guidelines  and AmerThe potential cardiovascular side effects of different classes of cancer therapies are elucidated, offering a comprehensive understanding of their dose- and time-dependent impacts.A pivotal section of this review emphasizes the diverse imaging modalities available for detecting cardiotoxicity. The roles of echocardiography, cardiac magnetic resonance imaging (CMR), cardiac computed tomography (CCT), and nuclear imaging techniques are explored, highlighting their strengths and potential limitations.The significance of each modality is further delineated across various conditions associated with cancer therapy, such as cardiac dysfunction, myocarditis, coronary artery disease (CAD), Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure (HF) with preserved ejection fraction (EF).Lastly, this review underscores the significance of long-term follow-up for cancer treatment survivors and hints at the promising future directions in the field, including the exploration of novel imaging markers like the PET/CT scan.The 2022 ESC guidelines  introducThe American College of Cardiology Cardio-Oncology and Cardiovascular Imaging Leadership Councils have presented an imaging definition of CTRCD that complements the clinical classifications of cardiotoxicity as described by the International Cardio-Oncology Society (ICOS) . These iAs previously outlined in the 2020 Heart Failure Association (HFA)/ICOS position paper  and latePatients who do not experience disease progression or have a poor prognosis in the first year following chemotherapy discontinuation are classified as long-term survivors and are assigned to a specific risk and surveillance category .Therefore, it is recommended to assess the cardiovascular status of cancer patients before, during, and after receiving cardiotoxic treatment. The frequency of cardiovascular monitoring should be tailored to the type of drug, treatment settings, combination with other therapies, and, most importantly, the patient’s risk of cardiotoxicity, which is a dynamic parameter that should be reassessed over time .For cardioprotection, the 2022 ESC guidelines suggest the use of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), betablockers, and statins for primary prevention in patients at high and very high risk (class IIa) .Currently, sodium–glucose cotransporter type 2 inhibitors (SGLT2i) are emerging as primary therapy for both HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) due to their multiple cardioprotective effects ,13. ChemIn mouse models, SGLT2i can prevent anthracycline-induced LV dysfunction through several mechanisms, including increased cardiac energy production, reduced oxidative stress, preservation of mitochondrial function, anti-inflammatory effects, and decreased cell death and myocardial fibrosis . In addiIncorporating SGLT2i into the management of cancer patients receiving cardiotoxic chemotherapy could be a crucial strategy for mitigating chemotherapy-related cardiac complications. Nevertheless, their precise role in clinical practice necessitates further investigation and randomized controlled clinical trials involving human patients undergoing cancer treatments.Anthracyclines , some of the oldest cancer drugs, are still used for various conditions like lymphoma, leukemia, osteosarcoma, and breast cancer. They work against cancer by disrupting DNA and RNA synthesis, generating free radicals that harm DNA, inhibiting topoisomerase II Top2), and altering histones. This toxicity is linked to their anticancer effects, including Top2 inhibition and reactive oxygen species (ROS) production , and alt.Anthracycline-related toxicity can be categorized as acute (within two weeks of treatment), early (within a year after therapy completion), and late (over a year after therapy). Cardiotoxicity can be dose-dependent (early and late) and reversible (acute) or challenging to reverse (early and late).2 or equivalent is considered high risk. In adults at high and very high cardiovascular toxicity risk, liposomal anthracyclines should be considered [Risk factors for anthracycline-induced side effects include being female, having pre-existing conditions , extremes of age (pediatric or elderly), combined therapy with microtubule inhibitors, and concomitant heart-related radiotherapy . Anthracnsidered .HER2-targeted monoclonal antibodies  play a crucial role in treating HER2-positive breast cancer, both in early and metastatic stages. Trastuzumab can also be used for patients with HER2-overexpressing metastatic gastric adenocarcinomas in combination with platinum-based chemotherapy and either capecitabine or 5-fluorouracil (5-FU).These antibodies block the HER-2/neureceptor, halting the activation of intracellular growth factors.Cardiac dysfunction arises from the disruption in signaling between the HER-2/ERBB2 receptor and the neuregulin ligand, a pathway responsible for growth, repair, and homeostasis.Cardiotoxicity typically emerges during therapy, is reversible, and can lead to left ventricular dysfunction in 15–20% of patients. Factors like simultaneous therapy with anthracyclines, age over 50, obesity, LVEF < 50%, and prior surgery increase the risk of cardiotoxicity .Fluoropyrimidines  are primarily used for treating gastrointestinal cancers and advanced breast cancer. The most common CTR-CVT associated with these drugs include angina pectoris, ECG abnormalities related to ischemia, arterial hypertension, Takotsubo syndrome, and myocardial infarct, even in patients with normal coronary arteries. Less common CTR-CVT events involve myocarditis, arrhythmias, and damage to peripheral arteries like Raynaud’s phenomenon and ischemic stroke.The incidence of myocardial ischemia can reach up to 10%. Various mechanisms, including coronary vasospasm and endothelial injury, contribute to 5-FU-induced myocardial ischemia. The risk of CTR-CVT significantly increases in cancer patients with pre-existing CAD .Vascular endothelial growth factor inhibitors (VEGF Inibitors) are available either as monoclonal antibodies , administered intravenously and targeting circulating VEGF, or as small-molecule tyrosine kinase inhibitors  taken orally, targeting VEGF receptors.An abnormal VEGF signaling pathway appears to play a crucial role in the development of various cancer types. VEGF inhibitors are typically employed in the treatment of renal, thyroid, and hepatocellular carcinomas.Hypertension is the most common cardiac side effect (with an incidence greater than 10%), and it is a dose-dependent class effect that can usually be reversed by discontinuing VEGF inhibitors. The risk is higher in patients with pre-existing hypertension, prior anthracycline treatment, advanced age, a history of smoking, hyperlipidemia, and/or obesity.Other common cardiovascular complications may include HF/LV dysfunction, QTc interval prolongation, and acute vascular events such as aortic dissection, stroke, arterial thrombosis, acute coronary events, and vasospasm ,11.Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL include Imatinib (1st gen)-Nilotinib (2nd gen)-Dasatinib (2nd gen)-Bosutinib (2nd gen)-Ponatinib (3rd gen).Chronic myeloid leukemia results from the abnormal activation of ABL1 kinase due to a chromosomal translocation. Small-molecule TKIs targeting BCR-ABL have been proven to be effective in chronic myeloid leukemia treatment. The toxicities associated with these TKIs are distinct and result from the ‘off-target’ effects of each drug. Dasatinib is linked to group 1 pulmonary hypertension (PAH), HF, and pleural and pericardial effusion. Nilotinib and Ponatinib are generally associated with vascular events. Second-generation BCR-ABL TKIs may induce QTc interval prolongation.The risk of cardiovascular toxicity is elevated in patients aged 65 years and those with underlying diabetes mellitus, hypertension, or pre-existing CAD ,11.Bruton TKIs  are used to treat lymphoid malignancies. Bruton TKIs play a crucial role in B-cell development. Ibrutinib, a first-in-class irreversible oral inhibitor of BTK, has proven to be highly effective in chronic lymphocytic leukemia and related B-cell malignancies.These disorders are usually diagnosed in elderly patients with more comorbidities. Ibrutinib has been associated with bleeding diathesis, infections and increased risk of arterial hypertension, atrial fibrillation and HF ,11.Proteosome inhibitors  are commonly employed in the treatment of multiple myeloma and mantle cell lymphoma.The proteasome’s function is to break down abnormal proteins tagged with ubiquitin. In cancer cells, this pathway is overactive. The anticancer mechanism of this group involves inhibiting the proteasome by binding to one of its subunits.The suggested mechanism of cardiotoxicity includes oxidative stress on cardiomyocytes leading to apoptosis or temporary endothelial dysfunction.Cardiovascular adverse events may encompass arterial hypertension, HF, acute coronary syndromes, arrhythmias, pulmonary hypertension, and thrombotic events. HFpEF can have a significant adverse effect, especially with carfilzomib. Pre-existing cardiovascular disease and concurrent administration of anthracyclines are risk factors for cardiac dysfunction ,9.Immune checkpoint inhibitors (ICI) are typically utilized in the treatment of advanced melanoma, metastatic kidney cancer, and non-small cell lung cancer. These therapies target immune checkpoints, which are proteins expressed in T cells that act to suppress their activation when they come into contact with healthy cells.ICIs are monoclonal antibodies that interfere with immune regulators, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) (such as Ipilimumab and Tremelimumab), programmed death-1 (PD-1) , and programmed death-ligand 1 (PD-L1) , found in cancer cells. This interference leads to an enhanced immune response, allowing T cells to attack and destroy cancer cells by preventing these checkpoints from binding with their partner proteins and inhibiting the ‘off’ signal. However, ICI treatment can also result in excessive T-cell activation against normal tissues, leading to immune-related adverse events.Immune-related cardiovascular complications may include severe myocarditis , myopericarditis, cardiac dysfunction/heart failure, arrhythmias, Takotsubo syndrome, or myocardial infarction. The mortality rate associated with cardiovascular toxicity is substantial. Adverse cardiovascular events typically manifest early in the treatment course and can occur after the first infusion, with most cases occurring within the first treatment cycles. However, later events have also been reported ,9,11.CART-cell therapy (Chimeric antigen receptor T cell) is an innovative approach in cancer treatment that involves modifying a patient’s own T-cells to target and destroy cancer cells. It is used for the treatment of acute lymphocytic leukemia and aggressive B-cell lymphomas.CAR-T therapy may have cardiovascular toxicity, primarily due to cytokine release syndrome and immune-related adverse events.Cardiac adverse event are LV dysfunction, HF, cardiac arrhythmias, pericardial effusion, Takotsubo syndrome and cardiac arrest ,11.Haematopoietic stem cell transplantation (HSCT) constitutes a potentially curative therapeutic option for many haematological malignancies.During the early phase following HSCT, atrial fibrillation is the most commonly observed cardiovascular event, although other cardiovascular complications can include HF, arterial hypertension, hypotension, pericardial effusion, or thrombotic events. Long-term adverse effects encompass diabetes mellitus, abnormal lipid levels, metabolic syndrome, arterial hypertension, HF, coronary artery disease, conduction abnormalities, and pericardial effusion.Acute graft versus host disease (GVHD) is linked to thrombosis and inflammatory damage to the heart muscle (myocarditis), HF, conduction irregularities, arrhythmias, and pericardial effusions. Meanwhile, chronic GVHD has been associated with an elevated risk of arterial hypertension, diabetes mellitus, and abnormal lipid levels .Alkylating Agents ) establish connections with DNA, hindering its replication and prompting cell apoptosis. They find application in the treatment of various cancers, including testicular, breast, ovarian cancer, leukemia, lymphoma, multiple myeloma, and sarcomas.Cisplatin, albeit infrequently, can lead to LV dysfunction and HF. This occurs because it necessitates a high intravenous volume to prevent renal toxicity, which may result in symptomatic HF in patients with pre-existing CV conditions. Cisplatin also heightens the risk of dyslipidemia, obesity, metabolic syndrome, and myocardial infarction in long-term survivors.Platinum-containing chemotherapy carries the potential for vascular complications, including vasospasms, myocardial infarctions, and both venous and arterial thrombosis.Microtubule inhibitors  are used to treat ovarian, breast, non-small cell lung, and prostate cancers.Their antineoplastic effect involves stabilizing guanosine diphosphate-bound microtubules, thus inhibiting cell division.Cardiovascular toxicity arises from the reduction in calcium amplitude in cardiomyocytes during contraction, diminishing cardiomyocyte contractility and resulting in LV dysfunction and HF. Microtubule inhibitors are also linked to an increased risk of stable angina and coronary artery disease (with a cardiac ischemia incidence of 1–5%) ,11.Radiotherapy (RT) is a valuable treatment modality used in a variety of cancer types, including breast, lung, esophagus, thyroid, prostate, mediastinal lymphoma, and head and neck tumors, often as part of a comprehensive therapeutic approach.Its efficacy lies in disrupting DNA, causing local inflammation, and promoting tissue fibrosis.However, RT can have detrimental cardiovascular consequences. Repeated episodes of ischemia due to inflammation can trigger microvascular endothelial cells in the pericardium to undergo fibrosis. RT also induces intravascular inflammation in epicardial coronary arteries, reducing oxygen and nutrient supply to the myocardium, leading to cardiomyocyte necrosis and fibrosis. Additionally, it contributes to a prothrombotic state, vasospasm, increased recruitment of monocytes and macrophages to the tunica intima, and greater inflow of lipoproteins, all of which accelerate existing atherosclerosis or initiate new atherosclerotic plaques.Vasculopathy typically presents as severe, diffuse, long, and concentric coronary lesions, often asymptomatic due to reduced pain sensation ,17.Cardiotoxic effects encompass pericarditis, CAD, peripheral artery disease (PAD), valvular heart disease , LV dysfunction, HFpEF, arterial hypertension, and occasionally, arrhythmias ,17,18.These effects may emerge years after completing therapy. The risk of cardiotoxicity is higher in cases involving a higher radiation dose (≥30 Gy), combined therapy with anthracyclines, heart irradiation, younger age (<25 years), prior cardiovascular dysfunction, and the presence of cardiovascular risk factors.CAD risk increases within a decade postRT, with left-sided breast cancer patients, in particular, facing a heightened risk of CAD, primarily in the distal part of the left anterior descending (LAD) coronary artery and diagonal artery, accounting for the majority of lesions ,19.The literature regarding the use of serum cardiac biomarkers for assessment of the risk of CTR-CVT before cancer therapy is limited and recommendations are primarily based on expert opinions. The 2022 ESC guidelines suggest that measurement of serum cardiac biomarkers, including cardiac troponin (cTn) I or T and natriuretic peptides (NPs)  can help assess the baseline CV risk in patients undergoing various cancer therapies . This assessment can aid in identifying individuals who may benefit from cardioprotective therapy.Baseline measurement of NPc and/or cTn is recommended in all patients with cancer at risk for CTRCD if the degree of change in biomarkers is to be used to detect CTRCD during treatment .However, in cancer patients and those undergoing cancer treatment, there are no universally defined cutoff values for cardiovascular biomarkers. In addition, NP and cTn levels may vary between laboratories and are influenced by factors such as age, sex, renal function, obesity, infections, and other health conditions such as atrial fibrillation and pulmonary embolism .Thus, any increase in biomarker levels must be interpreted by considering the patient’s clinical situation, including the time of cancer treatment and any comorbidities .However, a clear association between anthracycline-associated troponin increase and future development of LV dysfunction has been shown. A 2020 meta-analysis studied the utility of cTn and/or NPs in 61 studies with 5691 patients. Patients with cTn elevation after anthracycline treatment had a seven-fold increase in risk of LV dysfunction, with a sensitivity of 54%, specificity of 79%, and a very high negative predictive value of 93%. Mean BNP/NT-proBNP levels also increased in patients after treatment, but the available evidence did not consistently indicate prediction of LV dysfunction during chemotherapy [The 2022 ESC guidelines for patients on anthracycline therapy recommend measuring NP and cTn in subjects at high and very high risk of CTRCD at various times, including at baseline, before each course of treatment, and at 3 and 12 months after the end of therapy. Low-risk subjects can be monitored at baseline, potentially every other cycle during treatment, and possibly at 3 months after completion of therapy .Emerging biomarkers such as myeloperoxidase and micro-RNAs show promise for risk stratification of cardiotoxicity before cancer treatment .Biomarkers may help identify early signs of CTRCD, allowing for timely intervention. However, more research is essential to ascertain the best biomarkers and monitoring approaches.CV imaging plays a crucial role in identifying patients with subtle CV dysfunction, evaluating pre-existing cardiac conditions before initiating cancer therapy, and serving as a reference for tracking changes during treatment and long-term follow-up .Transthoracic echocardiography stands as the preferred imaging modality for baseline risk assessment. It offers quantitative evaluations of LV and right ventricle (RV)function, chamber size, LV hypertrophy, regional wall motion abnormalities, diastolic function, valvular heart diseases, pulmonary arterial pressure (PAP), pericardial diseases and LV GLS. These assessments are essential for influencing therapeutic decisions ,21.CMR is a valuable alternative for assessing cardiac function [When echocardiography is not available or proves inconclusive, function . CMR is CMRm encompasses pre-contrast T1-weighted (T1w) and T2-weighted (T2w) images to detect regions with increased signal intensity, indicative of fat and tissue edema, respectively. Late gadolinium enhancement (LGE) imaging facilitates the visualization and quantification of myocardial reparative fibrosis and scar tissue. Modern mapping techniques enable precise quantification of myocardial composition by measuring T1 and T2 relaxation times.Native (pre-contrast) T1 times reflect changes in myocardial extracellular water content, focal or diffuse fibrosis, and fat and amyloid content. Myocardial extracellular volume (ECV) quantification, derived from pre- and post-contrast myocardial and blood T1 values and corrected for blood hematocrit, serves as an indicator of diffuse interstitial fibrosis, provided other potential causes of increased extracellular space have been ruled out. T2 mapping is particularly useful for detecting edematous myocardium. Phase-contrast imaging aids in assessing the severity of valve regurgitation or stenosis ,23,24,25Multigated acquisition nuclear imaging (MUGA) can be considered as a third-line option when both echocardiography and CMR are unavailable for assessing LVEF. However, it should be used sparingly due to radiation exposure and its limitations in providing comprehensive information . CCT alsFunctional imaging tests for myocardial ischemia, including stress echocardiography, CMR, andnuclear myocardial perfusion imaging , are recommended for diagnosing the presence and extent of myocardial ischemia and assessing the need for therapeutic interventions ,9.Before initiating cardiotoxic cancer therapy, it is crucial to perform a baseline assessment of LV function to identify any underlying cardiac dysfunction within the 3 months preceding treatment initiation.Echocardiography remains the primary tool for detecting LV dysfunction, with a focus on accurately measuring LVEF. Three-dimensional (3D) echocardiography is the preferred method for assessing LVEF and cardiac volumes due to its enhanced accuracy and lower inter-observer variability (approximately 5–6%) ,30. WhenGLS, assessed through speckle tracking using three apical views, is a more sensitive and reproducible measure of LV systolic function than LVEF. It can detect subclinical cardiac dysfunction before abnormalities in LVEF become apparent. GLS is a valuable screening tool for risk stratification before cancer treatment and should be evaluated in all patients requiring baseline echocardiograms ,34,35. GThe SUCCOUR (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes) trial showed that initiating treatment with ACEI or ARBs and betablockers in patients undergoing cardiotoxic cancer therapy, based on a ≥12% relative reduction in LV GLS at any follow-up time point, results in a smaller decrease in LVEF compared to treatment after a decline in LVEF has already occurred ,37.However, it is important to note that there is some inter-vendor variability in GLS measurements of up to 3.7%, and GLS can be influenced by changes in loading conditions that commonly occur during chemotherapy, such as volume fluctuations due to intravenous fluids, vomiting, or diarrhea. Therefore, measuring systemic arterial blood pressure is recommended during resting echocardiography and should be included in the echocardiography report ,38.Myocardial work, which considers myocardial deformation and afterload, offers a more accurate assessment of cardiac function . IndicesWhile RV function has not traditionally been a part of the definition of cardiotoxicity, recent evidence indicates that RV abnormalities are prognostically significant in patients undergoing anthracycline and trastuzumab therapy . RV freeSeveral studies have demonstrated progressive impairment of diastolic function in patients treated with anthracyclines. Although it may precede systolic dysfunction, the prognostic value of diastolic dysfunction is modest .Left atrial strain, specifically reservoir and conduit reduction, frequently occurs early during anthracycline therapy and correlates significantly with routine echocardiographic diastolic parameters. This suggests a potential role in early cardiotoxicity detection .In patients receiving anthracyclines, a decrease in peak mitral annular systolic velocity (S’) has been observed early and persists for several years after treatment, indicating its potential as an early marker of cardiotoxicity .An increase in the Tei myocardial performance index, calculated as the sum of isovolumetric contraction and relaxation time divided by the ejection time , has beeDobutamine stress echocardiography has shown promise in identifying high-risk patients for cardiac dysfunction induced by chemotherapy drugs by detecting those with reduced LV contractile reserve ,54. HoweNon-invasive assessment of coronary flow reserve (CFR) in the LAD coronary artery during dipyridamole stress echocardiography could be a valuable tool in patients treated with anticancer drugs. Impaired CFR has been observed in patients receiving sunitinib treatment, and it correlates inversely with treatment duration and inflammation markers, suggesting that inflammation may contribute to cardiac dysfunction related to sunitinib ,57.If transthoracic echocardiography yields poor image quality, CMR is acknowledged as a screening method for chemotherapy-related cardiotoxicity due to its precision, reproducibility, and capacity to detect subtle changes in RV and LV function . The temMore recently, CMR-derived GLS, using feature tracking (FT), has demonstrated its ability to detect LV dysfunction before a decline in LVEF and to independently predict all-cause mortality across various cardiomyopathies . ReductiCMR measurement of LV mass also decreases following anthracycline administration, offering an additional biomarker for cardiotoxicity. This reduction in LV mass during treatment is attributed to at least a 40% reduction in cardiomyocyte size, partly offset by increases in ECV .Some small-scale studies employing CMR have also demonstrated early myocardial edema following anthracycline therapy using T2w sequences . The preAlthough fibrosis is a known consequence of anthracycline treatment, LGE is not commonly observed and is not associated with outcomes, likely due to the diffuse nature of anthracycline-mediated fibrosis, which may be interstitial and therefore not well visualized with LGE-based methods ,68.Diffuse myocardial fibrosis induced by anthracycline therapy can manifest several years after completing treatment and may be assessed using T1 mapping ,70. HoweCMR appears capable of detecting early inflammatory involvement (elevated native T1 and T2) and interstitial fibrosis and remodeling (elevated native T1 but not T2) ,25.The ECV also increases in patients after anthracycline therapy compared to healthy controls and may rise within the first few months after treatment ,71. ThisHistorically, MUGA has been used to assess LV systolic function due to its availability, accuracy, and reproducibility . CurrentRetrospective multiphase ECG-gated CCT can offer detailed morphological and functional information for both ventricles and may be considered an accurate and reproducible alternative to CMR ,27. FurtIt is clear that LVEF is an insufficiently sensitive parameter for prediction of HF and is incapable of detecting early dysfunction of myocardial contraction. The use of new parameters, such as GLS or myocardial work by speckle-tracking echocardiography or the evidence and quantification of myocardial edema and/or fibrosis by CMR helps us to recognize myocardial dysfunction early and to differentiate acute and late cardiotoxicity due to cancer therapy.The downward arrow indicates a decrease in parameter value indicative of CTRCD, while the upwardarrow indicates an increase in parameter value indicative of CTRCD.“Early” indicates that the parameter may alter early in CTRCD, while “later” indicates that the parameter alters later in CTRCD.Myocarditis is typically associated with ICIs, which have recently become a part of the treatment regimen for resistant malignancies . DiagnosWhen there is suspicion of ICI myocarditis, CMR imaging, including T1 and T2 mapping, and LGE, is recommended to aid in clinical decision-making. This includes determining whether to discontinue immunotherapy, the necessity of performing an endomyocardial biopsy and guiding the administration of high-dose steroids. The diagnosis of myocarditis on CMR is established using the updated Lake Louise criteria ,76. EndoIn situations where CMR is not available, fluorodeoxyglucose (FDG)–positron emission tomography (PET) imaging may also be considered for diagnosing myocarditis .CCT can be useful for ruling out obstructive coronary CAD when myocarditis is suspected .For individuals with ICI myocarditis, follow-up CMR at 3 to 6 months has prognostic value ,76.Functional tests for detecting myocardial ischemia, such as stress echocardiography, perfusion CMR, or nuclear myocardial perfusion imaging, should be conducted in symptomatic patients (those with stable angina or limiting dyspnea) when clinical suspicion of CAD is present. This is particularly important before initiating cancer therapies associated with vascular toxicity or RT .CCT can be employed to assess coronary atherosclerosis prior to commencing cancer therapy, aiding in the identification of the patient’s risk category for subsequent clinical management. For individuals undergoing chemotherapy, CCT serves to rule out acute coronary syndrome resulting from vasospasm, accelerated atherosclerosis, or thrombosis . CCT canIn the post-radiation/chemotherapy population, single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) plays a prognostic role in detecting obstructive CAD. This nuclear scan employs a pharmacological stress protocol with dipyridamole or dobutamine and TC-99m-tetrofosmin as a nuclear marker injected in two phases after pharmacological stress and later during a rest protocol. SPECT MPI does not require physical exercise, is not hindered by sonographic limitations, and can be performed immediately after radiation therapy.Patients with extensive CAD risk factors undergoing high-risk oncologic surgeries may benefit from traditional SPECT imaging for improved cardiac risk assessment.Positron emission tomography (PET MPI) is considered as the gold-standard technique for diagnosing myocardial metabolism and assessing microvascular function due to its ability to evaluate ischemia ,28.Takotsubo cardiomyopathy is more common in patients with cancer and it is associated with numerous chemotherapy agents.Echocardiography is usually the first test of choice, showing the specific wall motion abnormalities—typically (about 75%) with akinesis of the mid and apical LV segments and mid-ventricular (15–20%) and basal ballooning (1%)—and eventual RV involvement (which is a prognostic marker of unfavorable outcomes) ,11.CMR can be a helpful additional test to distinguish between other potential etiologies of cardiomyopathy, such as myocarditis. Typical CMR features include specific wall motion abnormalities and diffuse and extended myocardial oedema, in particular in the regions with akinesis and absence of significant irreversible tissue injury (LGE), although subtle fibrosis may be rarely seen ,22.Acute pericarditis, potentially accompanied by significant effusion that could lead to conditions like tamponade, has been linked to various chemotherapy drugs and intensive RT ,9,11. CMAfter undergoing RT, some patients might develop chronic pericardial issues, including constrictive pericarditis. CMR helps in identifying these conditions by showing signs like myocardial tagging, indicating parietal and visceral pericardium adhesion. The presence or absence of pericardial LGE can indicate whether the condition is inflammatory or fibrotic ,78. For Although rare, cancer therapy can lead to pulmonary hypertension, as observed with dasatinib , cyclophosphamide, and other alkylating agents ,9.Echocardiography is the initial imaging choice, with recommended reassessment every 3–6 months for patients receiving PAH associated therapy ,11.CMR is considered to be the gold standard for assessing right heart structure, function, tissue characterization , and vascular abnormalities ,23.CCT provides a 3D quantitative assessment of RV and can detect fatty infiltration when CMR is unavailable or unsuitable. CCT is also useful for ruling out underlying CAD and lung disease ,24.Arterial hypertension is a common, modifiable cardiovascular risk factor, and its presence, especially in combination with other comorbidities, is an independent prognostic factor for survival. VEGF inhibitors and TKI increase the risk of arterial hypertension and may destabilize previously controlled hypertension ,9,11.While echocardiography is the primary investigative tool, CMR can offer complementary insights into the cardiovascular consequences of hypertension, such as LV hypertrophy and myocardial fibrosis. CMR can also help exclude underlying secondary causes like renal artery stenosis and adrenal masses ,22,25.Valvular heart disease is a recognized complication of mediastinal RT, potentially affecting up to 10% of patients. However, modern treatment regimens have significantly reduced this number. There is typically a latent interval of 10–20 years between radiation exposure and the development of clinically significant heart valve disease, notably aortic stenosis and mitral regurgitation.Echocardiography is the primary diagnostic tool, offering both qualitative and quantitative assessment of stenotic and regurgitant valves.CCT and CMR can also aid in valve evaluation. CCT is particularly useful for stenotic valve planimetry and the assessment of suspected endocarditis, especially in conjunction with hybrid imaging like PET-CT.CMR can provide additional information, especially when echocardiographic measurements are inconclusive, allowing for the assessment of valve morphology, measurement of LV and RV volumes and function, and quantification of valvular flows and velocities using phase contrast sequences ,11,22,25The risk of HFpEF in breast cancer survivors increases with higher cardiac radiation exposure during RT. While HFpEF in breast cancer survivors is not extensively studied, some data suggest that coronary microvascular compromise may contribute to its pathophysiology ,17,18,31Echocardiography serves as the initial imaging modality for diagnosing diastolic LV dysfunction, defining cardiac structure and function, and grading diastolic dysfunction based on LV filling patterns and filling pressures. In cases where diastolic dysfunction is suspected but filling pressures are normal or echocardiographic findings are inconclusive, stress echocardiography can provide additional insights.CMR is valuable for uncovering underlying pathologies in HFpEF patients, and CMR-derived LGE and ECV measurements can enhance diagnostic and prognostic information ,16,17,20Future research should focus on improving HFpEF prevention and treatment by gaining a deeper understanding of its etiology and identifying contributing risk factors. When breast cancer survivors develop HFpEF, treatment primarily involves initiating guideline-directed medical therapy and addressing underlying comorbidities ,13,14,16First-line treatment for HFpEF includes SGLT2i, which have positive cardiovascular effects by promoting natriuresis, promoting diuresis, reducing blood pressure, and alleviating oxidative stress, inflammation, and myocardial fibrosis .Two large randomized clinical trials involving 5988 and 6263 patients  [Despite slightly different primary endpoints  both studies demonstrated a reduction from 18% to 21% in the rate of HF hospitalization and cardiovascular death with SGLT2 inhibitors  ,81.SGLT2ihave been shown to have a favorable safety profile in HFpEF, with no increased risk of hypoglycemia compared to their use in diabetes management. However, careful attention should be given to potential side effects like urinary tract infections and volume depletion, particularly in high-risk patients ,80,81.The introduction of SGLT2i represents a significant advancement in HFpEF management. Their unique mechanisms of action, proven clinical effectiveness, and favorable safety profile make them an appealing treatment option for a condition that previously lacked effective therapies.Ongoing research should continue to explore their full potential and refine their role in the comprehensive management of HFpEF.Cancer patients have a higher incidence of atrial fibrillation (AF), which can be attributed to various factors, including comorbid conditions like arterial hypertension and HF, older age , the direct effects of cancer , complications of cancer surgery , or as a side effect of certain anticancer drugs.Numerous classes of cancer therapies, including anthracyclines, fluoropyrimidines, VEGF inhibitors, TKIs targeting BCR-ABL, Bruton TKIs, proteasome inhibitors, ICI, alkylating agents, microtubule inhibitors, CART-cell therapy, and immunomodulatory drugs, can induce AF .Patients with both cancer and AF have an elevated risk of systemic thromboembolic events (stroke), major bleeding, intracranial hemorrhage, HF, and overall mortality .2DS2-VASc score , also apply to cancer patients. However, cancer patients with AF may have a higher thromboembolic risk than those without cancer, potentially underestimating their risk. According to 2022 ESC guidelines, anticoagulant therapy may be considered for men with a CHA2DS2-VASc score of 0 and women with a score of 1 (Class IIb), after assessing bleeding risk using the HAS-BLED score [The criteria for long-term anticoagulation in the general population, as determined by the CHAED score ,82.In terms of stroke prevention, non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over low-molecular-weight heparin (LMWH) and vitamin K inhibitors in cancer patients without a high risk of bleeding, severe kidney dysfunction, or significant drug interactions (Class IIa) . It is cVentricular arrhythmias (VAs) are relatively infrequent among cancer patients, but their occurrence rises in individuals with advanced cancer and CV comorbidities. They can result from the direct impact of cancer treatments on ventricular action potential channels or from chronic arrhythmic conditions triggered by cancer, inflammation, pre-existing cardiovascular conditions or new CTR-CVT .The standard upper limit for QTc values is 450 ms for men and 460 ms for women. QTc intervals that extend beyond 500 ms are associated with a threefold higher risk of developing Torsades de Pointes (TdP). The 2022 ESC guidelines for cardio-oncology categorize risk factors for prolonged QTc and VAs into two groups: correctable and non-correctable. Correctable factors include medications that lengthen QTc , bradycardia, and electrolyte imbalances caused by cancer treatments. Non-correctable factors include age over 65, female gender, family history of sudden cardiac death, congenital long QT syndrome (LQTS), and pre-existing renal or liver disease ,82.Cancer therapy-induced VAs are primarily associated with QTc prolongation, which can lead to TdP. The 2022 ESC guidelines offer a simple mnemonic, “AAGNO P-R-S-TV”, to recall ten high-risk drugs for QT interval prolongation  ,82,83.A 12-lead ECG is recommended following any dose increase inQTc-prolonging cancer therapy. According to the current ESC guidelines, QTc interval changes exceeding 60 ms, as long as QTc remains below 500 ms, should not hinder cancer treatment. When calculating QTc in cancer patients, the Fridericia formula is recommended due to its lower margin of error in both high and low heartrate conditions .Reversible causes of prolonged QT intervals should be addressed, with weekly ECG monitoring, VA risk assessment during treatment and consideration of alternative therapies. Management of anticancer therapy-induced VAs should align with general guidelines for VA management. Betablockers and class IB antiarrhythmics are suggested as the safest options, especially when the cancer drug is known to cause cancer therapy-related cardiac dysfunction. Amiodarone is favored for patients with structural heart disease or hemodynamic instability. Therapy decisions should be personalized, taking into account factors such as complication risk and projected life expectancy ,82.Assessment of CV risk at the conclusion of cancer therapy is crucial. Asymptomatic survivors showing new or persistent abnormalities at this stage are deemed at high risk for future CV events and require long-term monitoring.Certain cancer treatments carry the highest risk of long-term CV toxicity, notably anthracycline and RT involving the heart. Progressive RT-related CV toxicity tends to manifest 5–10 years posttreatment, significantly increasing the risk of CAD and HF, with an incidence up to six times higher than in the general population.Late CV complications are also observed in survivors who underwent HSCT, with the incidence of HF increasing up to 14.5% in women 15 years after HSCT. Risk factors for CV dysfunction postHSCT include age, anthracycline dose, chest radiation exposure, arterial hypertension, diabetes mellitus, and smoking.The timing and frequency of cardiac surveillance depends on the risk for CTR-CVT as per the latest ESC guidelines. Ideally, the same imaging modality used for LV systolic function assessment before antineoplastic therapy should be used for ongoing monitoring.A reasonable approach includes yearly or biannual imaging follow-up after therapy completion, especially for high-risk patients with CV risk factors or extensive cardiotoxic treatments.The surveillance interval can be shortened if cardiac dysfunction is observed. In cases of metastatic disease and long-term treatment, the frequency of imaging surveillance may be reduced.Currently, there is no recommendation for lifelong surveillance in survivors of trastuzumab and other targeted cancer therapies beyond 10 years unless other indications arise ,11.18F-FDG is predominantly used in oncological PET/CT scans. Under significant stress, heart cells might elevate their glycolytic metabolism. The level of myocardial18F-FDG uptake as assessed by the 18F-FDG PET/CT scan could potentially signal early cardiomyocyte changes that anticipate cardiac dysfunction, marking it as a potential tool in the early detection of cardiotoxicity [Exploring new cardiovascular imaging markers to identify cardiotoxicity and deepen our comprehension of its pathophysiology is a vital research area. The PET/CT scan, offering both anatomical and metabolic details, stands out as a promising diagnostic tool. The glucose analogue toxicity .Lastly, we think that by utilizing deep learning, artificial intelligence has the potential to streamline and enhance various aspects of imaging processes. It can automate mundane tasks, boost precision and consistency, and optimize efficiency across diverse imaging techniques. Furthermore, broader artificial intelligence applications extend to integrating clinical and laboratory parameters with multi-mode imaging data, aiding in the characterization of individual phenotypes and the improved identification and prediction of cardiovascular risks and potential treatment responses in cardio-oncology patients.The interplay between cancer treatment and the cardiovascular system is complex. A multidisciplinary approach using advanced multimodality imaging offers immense potential in pre-treatment risk stratification, early detection of cardiovascular injury during therapy and monitoring the long-term cardiovascular effects posttherapy.The newly introduced terminologies and classifications from renowned cardiology institutions emphasize the importance of understanding and classifying cardiovascular toxicity due to cancer treatment.With different classes of cancer therapies presenting various cardiovascular effects, a comprehensive grasp of their dose- and time-dependent impacts is crucial. Echo, CMR, MUGA, and CCT have emerged as significant modalities to detect subtle cardiovascular dysfunctions, assess pre-existing conditions before commencing cancer therapy, and longitudinally track changes during and posttreatment.We accentuate the importance of a multidisciplinary approach for risk-benefit discussions before starting potentially cardiotoxic treatments, especially for high-risk patients. Furthermore, continuous cardiovascular monitoring tailored to individual treatment and patient-specific risks is underscored.While the current imaging techniques provide profound insights, the exploration of novel imaging markers like the PET/CT scan points towards the promising future directions in the realm of cardio-oncology.


The aim of this review is to identify a preventive strategy in order to minimize the risk of adverse events in patients with coronary syndromes and acute exposure to high-altitude. For this purpose we searched the electronic database of PubMed, EMBASE, and Web of Science for studies published in the last 30 years in this field. The conclusions of this review are: patients with stable coronary artery disease on optimal treatment and in a good physical condition can tolerate traveling to high altitude up to 3500 m; on the other hand, patients with unstable angina or recent myocardial infarction no older than 6 months should take less interest in hiking or any activity involving high altitude. Air-traveling is contraindicated for patients with myocardial infarction within previous 2 weeks, angioplasty or intracoronary stent placement within previous 2 weeks, and unstable angina or coronary artery bypass grafting within previous 3 weeks. The main trigger for sudden cardiac death is the lack of gradual acclimatization to high-altitude and to the exercise activity, and the most important risk factor is prior myocardial infarction. High-altitude (HA) locations (more than 2500 m above sea level) are reached by millions of people on a daily basis, aspect largely due to the ease of transport in recent years, mainly by air travel. Mountain areas cover 24% of Earth’s surface: 33% of Eurasia, 19% of South America, 24% of North America, and 14% of Africa ..7].A small study showed that the exposure to intermittent hypobaric hypoxia could improve myocardial perfusion in patients with severe stable CAD. Six months after coronary bypass surgery, 6 patients were exposed to simulated hypobaric hypoxia, using a multi-place hypobaric chamber. During 14 sessions (each session consisting of 4 h of progressive hypoxia exposure per week), patients were progressively exposed to simulated altitude starting at 2400 m (in the first week) and eventually reaching 4200 m (for the last 5 session) . The 14 One important study refers to the patients after myocardial infarction. The 16 patients after MI and 10 normal volunteers underwent a 1-day trip from low altitude (540 m) to high altitude (3564 m Swiss Alps). In patients with MI, the exposure to high-altitude was associated with the increase in sympathetic activity and with a reduction in parasympathetic tone. Patients with MI had lower stroke volume, lower cardiac output, and a lower low-frequency or high-frequency ratio, as well as increased total peripheral resistance compared with normal volunteers .The mental stress which increases heart rate, systolic and diastolic blood pressure, and cardiac output has an important role after MI. Therefore, one of the hypothesis of this study is that after MI patients may have an impaired ability to adapt the autosomic nervous system to acute high-altitude exposure and that mental stress might magnify this effect. In conclusion, MI patients exhibited higher sympathetic activity, lower parasympathetic counter regulation, which increases the arrhythmogenic risk .Another study that included 768 patients with acute coronary syndrome (ACS) aimed to evaluate the prevalence of risk factors and complications arising in case of exposure to high-altitude (1500–3500 m above sea level). In the 384 patients with ACS exposed to high-altitude, history of hyperlipidemia, history of CAD, and diabetes mellitus was significantly higher at higher altitude. Further, ACS at younger age, stroke, and reduced left ventricular ejection fraction occur more commonly in high-altitude .Hematologic findings among ACS patients exposed to high-altitude was particularly interesting, at this category of patients the level of hemoglobin, hematocrit, and white blood cell being significantly higher .In athletes with cardiovascular diseases, after trauma, sudden cardiac death is the predominant cause of death, and the most important risk factor for this is the history of myocardial infarction .Patients with CAD and high-altitude exposure should be counseled to hydrate and temper increases in exercise load, to facilitate acclimatization . AdditioAntianginal drugs should be administrated to relieve symptoms, but there are some limitations. Non-selective beta-blockers can reduce the oxygen saturation of hemoglobin and so they limit the ability to exercise. Selective beta-blockers does not generate such effects. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) reduce renal secretion of erythropoietin and limit hematocrit growth. Moreover, ACEI and non-selective beta-blockers by acting on ß2 adrenergic receptors, reduce gas diffusion in the alveoli and hyperventilation caused by hypoxia. A drug that can be used in patients with ischemic heart disease at high altitude is acetazolamide, which compensates for the reduction in oxygen supply to the heart muscle .Some conditions related to air-traveling may increase the risk for ischemia and arrhythmia. Mental stress and anxiety—that increase the sympathetic tone, together with dehydration and prolonged immobility—that increase the thrombotic risk, may lead to cardiovascular events .Due to the pressurization, cabin pressure corresponds to an altitude that is never higher than 3084 m , generally between 1524 m and 2134 m (5000 ft and 7000 ft) for typical commercial passenger flights. During a flight, cabin pressure is reduced to 565 mmHg which corresponds to an arterial saturation of 90% .Air-traveling is contraindicated for patients with myocardial infarction within previous 2 weeks, angioplasty with intracoronary stent placement within previous 2 weeks, unstable angina or coronary artery bypass grafting within previous 3 weeks .Thomas et al. studied a group of 213 patients with history of acute myocardial infarction, in a stable clinical condition, transported by commercial airlines. There were some cases of asymptomatic hypoxia, correctable with oxygen administration, some cases of angina pectoris resolved after sublingual administration of nitroglycerin. There were no significant differences between safety of transporting patients after ST-segment elevation myocardial infarction and non-ST segment elevation myocardial infarction, with or without revascularization [-very low risk: patients under 65 years old, first event, successful reperfusion, left ventricular ejection fraction (LVEF) > 45%, no complication, and no cardiac investigation or intervention pending;-low or medium risk: LVEF 40–45%, no symptoms of heart failure, no evidence of inducible ischemia or arrhythmia, and no further cardiac investigation or intervention pending;-high risk: LVEF < 40% with sigh and symptoms of heart failure, pending further investigations for revascularization or device therapy.The British Cardiovascular Society concluded that passengers with acute coronary syndrome should be stratified into 3 risk groups:The passengers with very low can fly after 3 days and those with medium risk after 10 days. For the ones at high risk it is necessary to stabilize the medical situation and delay HA exposure for a minimum of six weeks .A list with some general recommendations from European Society of Cardiology, American Heart Association and British Cardiovascular Society is presented in There are several factors that have an important role in stratifying the risk of patients with CAD in case of exposure to HA: age, sex, the presence of other coronary risk factors , the association of other cardiovascular comorbidities , or extracardiac comorbidities . By far, however, the essential factor involved in quantifying the prognosis of these patients is the type of coronary damage: acute or chronic. Patients with acute coronary syndrome, and especially with prior myocardial infarction, have a significantly higher risk of developing complications in case of exposure to HA ; severe pulmonary hypertension; thromboembolic event during the past 3 months; ICD implantation or ICD intervention for ventricular arrhythmias in the past 3–6 months .-pay strict attention to taking the usual medication;-adequate hydration and avoid alcohol;-plan a slow ascent to allow time for acclimatization;-do not exercising in the first day at altitude and planning out gradual increases in intensity;-plan load weight in a conditioned climber not to exceed 32% of body weight;-plan to relax and good sleep;-wear a pulse oximeter to track peripheral oxygen saturation and heart rate;-limitation of ascent and exercises at the threshold of symptoms—angina, dyspnea;-remember that descent is the safest and quickest path to resolution of altitude-related symptoms .Advice for patients:The incidence of sudden cardiac death (SCD) in general population varies between 50 and 100 per 100,000, being higher in man than women and increasing with age. Coronary artery disease accounts for more than 80% of SCD. Sudden cardiac death represents the most important and dramatic complication which can occur at CAD patients with chronic or acute exposure to HA. It appears more frequently in the case of exercise or sports activities in high altitude, the main mechanism of sudden cardiac death being ventricular tachycardia without pulse and, respectively, ventricular fibrillation .The main trigger for SCD is the lack of gradual acclimatization to HA and to the exercise activity. Almost 50% of all SCDs recorded in the Austrian Alps occurred in the first day of hiking or skiing . Sleepin2 requirement, which in the conditions of preexisting CAD can cause acute myocardial ischemia and ventricular arrhythmias. Moreover, the activation of sympatho-adrenergic system might also raise the risk of ventricular fibrillation. Another important risk factors are: prior myocardial infarction, coronary artery disease, arterial hypertension, diabetes mellitus type 2, and hypercholesterolemia [The SCDs were most frequently observed in the late morning hours, and related with increasing time from the last food and drink intake. Therefore, this facts suggest that physiological stress factors  causes the activation of the sympathetic vegetative nervous system with the increase in the release of catecholamines, which determine a multitude of negative effects: the increase in heart rate, the increase in blood pressure and in the myocardial Oerolemia .In a case-control study of 68 skiers who lost their lives to SCD, compared with 204 controls, those with a prior myocardial infarction had a 93 times higher adjusted SCD risk, those with hypertension a 9-fold higher risk, and those with known CAD without prior myocardial infarction a 4.8-fold increased risk .The most important preventive measures for SCD include: medical examination including stress test, appropriate physical preparation, pharmacological therapy of CAD and cardiovascular risk factors, progressive acclimatization to HA, and exercise activity .The data on the exposure of patients with CAD to HA are contradictory. Some authors recommended caution, or even discourage physical activity at HA, especially in those with impaired coronary flow reserve ,53,54. SIn this review we tried to underscore some of the meaningful research in the field. The conclusions of this review are: patients with stable coronary artery disease on optimal treatment and in a good physical condition can tolerate traveling to high altitude up to 3500 m; on the other hand, patients with unstable angina or recent myocardial infarction no older than 6 months should take less interest in hiking or any physical activity involving high-altitude; air-traveling is contraindicated for patients with acute coronary syndrome, angioplasty with intracoronary stent placement at least 2 weeks, and for coronary artery bypass grafting within previous 3 weeks. The main trigger for SCD is lack of gradual acclimatization to HA and to the exercise activity, and the most important risk factor is prior myocardial infarction.The correct stratification of cardiovascular risk and the adaptation of exposure to HA in accordance with them, as well as the knowledge, prevention and treatment of predisposing conditions and trigger factors for SCD, can significantly improve the prognosis of patients with CAD in case of exposure to high-altitude.The small number of studies published in this field, as well as their high degree of variability  make it almost impossible to carry out a meta-analysis in accordance with the current scientific rigors.


Overall, TEER was associated with improved cardiac performance, LA function amelioration, and reduced arrhythmic burden.Transcatheter edge-to-edge repair (TEER) currently represents a valuable therapeutic option for patients with severe mitral regurgitation (MR) considered at high surgical risk. Besides symptoms and left ventricular (LV) echocardiographic improvements upon TEER, it has been postulated that left atrial (LA) function plays a prognostic role. The aims of our study were to evaluate LA changes after TEER, measured by two-dimensional speckle-tracking echocardiography analysis (2D-STE), their association with atrial fibrillation (AF) occurrence, and relative arrhythmic burden. We considered in a single-center study 109 patients affected by symptomatic severe MR undergoing TEER from February 2015 to April 2022. By 2D-STE, LA reservoir (R_s), conduct (D_s), and contractile (C_s) strains were assessed along with four-chamber emptying fraction (LAEF-4CH) before, 1, 6, and 12 months following TEER. Statistical analysis for comparison among baseline, and follow-ups after TEER was carried out by ANOVA, MANOVA, and linear regression. Successful TEER significantly improved LV dimensions and LA performances, as indicated by all strain components, and LAEF-4CH after 1 year. Strikingly, a significant reduction in arrhythmic burden was observed, since only one case of subclinical AF detected by a previously implanted cardiac electronic device was found in the cohort of sinus rhythm patients ( Mitral regurgitation (MR) is an abnormal systolic reversal of blood from the left ventricle (LV) into the left atrium (LA) due to incomplete closure of the mitral valve . It reprHowever, early recognition, classification of etiology, and appropriate timing of critical interventions in patients presenting with suspected severe MR may result in better long-term outcomes ,13,14. TFurther than staging MR, echocardiography might provide important advancements in understanding LA deterioration and the development of atrial cardiomyopathy ,16. MoreLA remodeling is a response of cardiomyocytes to various stressors including MR that causes volume overload. In this circumstance, both structural  and cellular  changes occur. These alterations, together, promote nonuniform impulse propagation that is a substrate for AF maintenance ,15.Therefore, we conducted a study on the role of transcatheter mitral valve implantation in patients with severe MR and contraindications for surgery or high operative risk for addressing the beneficial effects on LA and LV geometries by reducing the atrial and ventricular arrhythmias occurrence.n = 109) not amenable to surgical repair were enrolled at the Department of Cardiology of the Magna Graecia University of Catanzaro from February 2015 to April 2022 for the TEER procedure. The main inclusion criteria, according to the COAPT trial . More in detail, in the post hoc analysis, R_s (baseline 10.7 ± 5.7%) showed a major significant improvement after 12 months’ follow-up . Similar results were obtained for D_s , e.g., in the post hoc analysis, from −6.7 ± 4.4% at baseline to −9.7 ± 4.5% at 12 months follow-up; p = 0.008. On the other hand, C_s did not show significant variation between groups , but in the post hoc analysis, there was a slight improvement, although it did not reach a significant difference between baseline −5.2 ± 5.1% vs. 12 months’ follow-up −7.8 ± 5.3%; p = 0.11. There was also a clear improvement of LAEF−4CH . In post hoc analysis, it was more evident between baseline and 12 months’ follow-up . Multivariate analysis provided differences in basal R_s based on patient rhythm, F  = 3.11, p = 0.006; Wilk’s Λ = 0.114, partial η2 = 0.515. In post hoc tests, a significant difference was found between sinus rhythm vs. AF permanent subgroups at baseline , at 1 month , at 6 months , and at 12 months  follow-ups.The design of this study composed of multiple follow-up points demonstrated that LA geometry and function proceed through a dynamic phenomenon. In fact, there were significant differences between all the follow-up windows for R_s [F  = 12.57; n = 34), no paroxysmal (n = 18) nor persistent case was added during follow-up after TEER. Average HR at follow-up was 69 ± 14 bpm for the entire enrolled population. In patients with paroxysmal AF, no progression to a persistent pattern was observed, while after intraprocedural cardioversion, sinus rhythm was reached and maintained in all patients (n = 9) that were affected by a persistent form. Mean CHA2DS2VASc was 4.5 ± 1.2. A total of 43 AHREs were detected at device interrogation of a patient in the sinus rhythm group  was significantly reduced as well as ventricular rate  in the permanent AF group . Linear regression demonstrated that R_s significantly predicted AF burden at baseline: the fitted regression model was AF burden = 25.6 − 0.8 * (R_s). The overall regression was statistically significant  = 31.9, p < 0.0001; β = −0.8, p < 0.0001).There was a good correlation between paroxysmal AF burden and R_s: −0.808 (NSVT episodes in AF patients were detected in 14.7% of cases (9/61) at baseline; their incidence was nearly halved  after MR improvement. Malignant ventricular arrhythmias such as sustained VTs or ventricular fibrillation were discovered in two patients from the AF group (3.3%) at baseline, without any repetition nor additional finding after MR transcatheter therapy.Since the first studies conducted, MR treatment with TEER has proven effective and safe, leading to a reduction in the severity of MR and an improvement in clinical status and quality of life in selected high-risk surgical patients ,10.Most likely, the reduction in the severity of the MR causes favorable hemodynamic changes in the left and right cardiac chambers, and such changes eventually affect clinical status and patient outcome ,13,14.The benefits resulting from TEER in terms of global improvement of cardiac function assessed by basal and advanced echocardiographic imaging modalities have been extensively described ,27. Moren = 27) did not progress through permanent form, and that improved LA geometry was associated with somehow reduced AF average ventricular rate and reduced total burden as well  improves LA function and (2) ameliorates longitudinal strain, and (3) LA strain assessment correlated with stabilization (in persistent and permanent AF) and even reduction  of the arrhythmic burden. Besides reservoir, conduct, and contractile functions, LA mediates cardiovascular homoeostasis through neurohormonal determinants that affect the electrophysiological properties of the atrial cardiomyocytes; LA remodeling in AF-related MR leads to loss of normal sympathoinhibition , which pFurthermore, at baseline, no differences in LA strain among patients with paroxysmal, persistent, and sinus rhythm were detected; this can be explained by the fact that LA function, per se, is not a primary element of steady state cardiac output . HoweverDifferent MR etiology  did not affect LA strains at baseline nor during follow-up, probably because all the subgroups represent chronic clinical settings that cause similar structural alterations in terms of derangement and fibrosis deposition.Finally, positive remodeling of LA and amelioration of LA function, especially in cases where structural alterations are not in the advanced phase, contributed to avoiding new-onset AF in patients with severe MR and in maintaining sinus rhythm, with the observed net result of reduced arrhythmic burden. One might speculate that there was a reduction in the sympathetic adrenergic overdrive that characterizes HF patients, including those candidates for TEER. Like chronic AF patients, arrhythmic burden of paroxysmal AF was found reduced in the current study, as well as a shorter duration of the episodes in persistent forms. In all cases, a more compensated state could have co-participated in cardiac rhythm stabilization, including heart rate reduction. On the other hand, it could be also considered that TEER heightens the cardiovascular response to pharmacologic agents in HF.Among the main limitations of the study, it must be acknowledged that the retrospective nature and the relatively small sample size do not confer to this work a comprehensive vision of the independent impact of atrial mechanics on cardiovascular outcomes. Also, due to inherent limitations of the 2D-STE technique, it was not possible to conduct STE analysis in all patients considered at the beginning of the enrollment, since those cases with poor image quality, as well as those with a too-low frame rate or other artifacts, have been discarded. The duration of follow-up of one year might be underestimating more severe outcomes such as the risk of death and HF hospitalization. One last limitation might be due to the relative role of optimal medical therapy , which mTEER caused a favorable atrial remodeling in the months following MR reduction as it was detected by 2D-STE, which allowed highlighting an improvement in the reservoir phase (strain reservoir) and in the conduction strain in postintervention follow-up. The reservoir strain represents the most effective 2D-STE parameter that can be detected in early phases after TEER and LA function amelioration. Furthermore, LA-positive remodeling contributes to limiting the incidence of ventricular and atrial tachyarrhythmias, mostly AF. Accurate selection of cases before invasive procedures is mandatory for identifying those patients who could benefit more from multiple therapies such as TEER and electrical nonpharmacologic therapies for AF.


A twist value higher than 11° has a 76.9% specificity and a 72.7% positive predictive value for reverse remodelling at 6 months.Background: The left ventricular (LV) remodelling process represents the main cause of heart failure after a ST-segment elevation myocardial infarction (STEMI). Speckle-tracking echocardiography (STE) can detect early deformation impairment, while also predicting LV remodelling during follow-up. The aim of this study was to investigate the STE parameters in predicting cardiac remodelling following a percutaneous coronary intervention (PCI) in STEMI patients. Methods: The study population consisted of 60 patients with acute STEMI and no history of prior myocardial infarction treated with PCI. The patients were assessed both by conventional transthoracic and ST echocardiography in the first 12 h after admission and 6 months after the acute phase. Adverse remodelling was defined as an increase in LVEDV and/or LVESV by 15%. Results: Adverse remodelling occurred in 26 patients (43.33%). By multivariate regression equation, the risk of adverse remodelling increases with age (by 1.1-fold), triglyceride level (by 1.009-fold), and midmyocardial radial strain (mid-RS) (1.06-fold). Increased initial twist decreases the chances of adverse remodelling (0.847-fold). The LV twist presented the largest area under the receiver operating characteristic (ROC) curve to predict adverse remodelling (AUROC = 0.648; 95% CI ,  Worldwide, coronary artery disease is the leading cause of mortality, and its prevalence is recognised as an upward trend. Nevertheless, in Europe, in the last 30 years, there has been a tendency for a decrease in ischaemic heart disease mortality . FurtherHeart failure (HF) is both the most common complication and also the most important prognostic element in patients with STEMI ,6. The pThe LV myocardium consists of three layers, and there is a difference in transmural damage after a myocardial infarction (MI). The ischaemic process begins in the endocardium and progresses as a wave front to the epicardium, the first layer being the most-affected .Over the years, the role of echocardiography in the evaluation of patients with MI has been crucial. As echocardiographic techniques have improved, it has been possible to develop new methods, such as speckle-tracking echocardiography. Moreover, the study of individual myocardial deformation at the level of the three myocardial layers is a promising tool in the study of LV function.The aim of this study was to identify the echocardiographic parameters with high sensitivity and specificity for early identification of the progression of REM after STEMI. We sought to assess the alteration in LV rotational characteristics by regional myocardial wall motion abnormalities after STEMI. Moreover, we hypothesised that the difference between the myocardial layers and the combination of different parameters obtained from speckle-tracking echocardiography could be important prognostic factors to predict REM. Differences in layer-specific strain values could be explained by human heart distribution of fibres that present various angles. Fibre distribution has angles varying from about 60°  at the inner surface to about–60° at the outer surface. The ratio of circumferentially to longitudinally oriented fibres is 10:1, increasing from the apex to the base . TherefoA crucial aspect of the LV function is cardiac rotation during systole. A wringing action is produced by the LV muscle fibres that are angled from a right-hand helix in the subendocardium, to a left-hand helix in the subepicardium ,15. WhenIn patients with anterior wall MI, the apical peak circumferential strain is severely reduced when associating LV systolic dysfunction compared with those with preserved systolic function . FurtherMechanical dispersion (MD) represents a marker derived from 2D STE (2D speckle-tracking echocardiography) and reflects contraction heterogeneity. In normal circumstances, all myocardial segments have broadly similar contraction durations; therefore, the values for MD are normally low. Patients with ventricular arrhythmias and ischaemic and nonischaemic cardiomyopathies have higher values of MD than those that did not present ventricular arrhythmias . In addiWe prospectively analysed 200 patients with STEMI and PCI  in sinus rhythm, hospitalised at the Cardiology Department of Timisoara Institute of Cardiovascular Diseases, in the period of December 2018 to December 2021. We excluded patients with inadequate echocardiographic images that impeded accurate measurements, open-chest surgery, previous myocardial infarction, patients with a cardiac pacemaker and/or implantable cardioverter defibrillator, malignant neoplasia, and those with a life expectancy <1 year. The remaining 151 patients formed our study population. Unfortunately, due to the problems caused by the COVID-19 pandemic, we could not re-evaluate all of these patients, and the final cohort consisted of 60 patients. At follow-up, the patients were divided into two groups: patients who suffered adverse remodelling and patients with reverse remodelling. Those who did not fit into any category were defined as normal (no remodelling).Patients were treated with beta-blockers, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor II blocker (ARB), spironolactone, statins, and dual antiplatelet therapy, according to current European guidelines. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Institute of Cardiovascular Diseases Timisoara (8461/04.12.2018). All patients provided written informed consent for participation in the study.The following clinical variables were recorded at hospital discharge: age, sex, body mass index, systolic arterial pressure, and heart rate. Furthermore, high-sensitivity cardiac troponin I level, time of peak CK, thrombolytic therapy, and TIMI flow before and after PCI were recorded. For study purposes, five cardiovascular risk factors were considered as follows: hypertension , cardiovascular disease heredity, smoking , diabetes mellitus (fasting glycemia >126 mg/dL or in drug treatment), and hypercholesterolemia (>200 mg/dL or in drug treatment).The patients underwent a transthoracic echocardiography in the first 12 h after admission, at rest, in the left lateral decubitus position. All the echocardiograms were performed before myocardial revascularisation. Both conventional two-dimensional echocardiography and speckle-tracking echocardiography were performed at baseline and follow-up. All measurements were performed by an experienced echocardiographer with an ultrasonographic system  equipped with a multifrequency transducer. LV ejection fraction (LVEF) was calculated using the modified Simpson’s biplane method, in apical two- and four-chamber views . These mThe left atrial (LA) volume was also determined by planimetry, using the biplane method, and indexed to the body surface. Systolic pulmonary artery pressure (SPAS) was calculated using the tricuspid regurgitation flow pressure and the right atrial pressure, estimated according to the inferior vena cava dimensions and respiratory variability. The mitral flow patterns were recorded from the apical four-chamber view using a 4–5 mm pulsed Doppler sample volume placed between the mitral leaflets’ tips, in diastole. Five consecutive cardiac cycles were recorded, with a horizontal sweep of 100 mm/s. The peak velocities of early diastolic mitral flow (E wave), and late diastolic mitral flow (A wave) were measured during end-expiratory apnoea. The results were averaged over the velocities recorded for the five consecutive cardiac cycles.For TDI parameter evaluation and measurement (m/s)—peak systolic tricuspid annulus velocity (tricuspid annulus s’), peak systolic mitral annulus velocity , and peak early (e’) and late (a’) diastolic mitral annular velocity, the TDI program was set in pulsed-wave Doppler mode  with a 4Myocardial contractility was categorised into four grades: normokinesia, hypokinesia, akinesia, and dyskinesia.To assess both the three types of strains  and the layer-specific strain, the apical four-chamber and two-chamber views and long-axis and short-axis views  were recorded with a frame rate of 60–80 frame/s during baseline and follow-up echocardiographic evaluations. While acquiring images, the LV basal short-axis view was identified by the presence of mitral leaflets, while excluding the mitral annulus, and the apical view was identified by the presence of a LV cavity in the absence of papillary muscles. We made every effort to obtain the LV cross-section as circular as possible. Then, strain analysis was performed with the off-line software . After manual tracing of the endocardial border of the LV in three apical images, endocardial, midmyocardial, and epicardial segmental and global longitudinal strains (GLSs) were obtained using LSendo, LSmid, and LSepi, respectively. Basal and apical LV radial and circumferential peak strains  were defined as the mean strain of the six basal and four apical parasternal short-axis segments. Rotation (degrees) was obtained at the basal level and the LV apex. The ratio between the endocardium and epicardium was also calculated according to the difference between LSendo and LSepi. LV twist was defined as the net difference (in degrees) of apical and basal rotations at isochronal time points and was autocomputed by the software from the values of the basal and apical rotations. A pulse-wave Doppler tracing obtained from the LV outflow tract was used to identify the timing of aortic valve opening and closure. In order to verify the inter- and intraobserver variability speckle-tracking measurements, they were performed by one observer at two separate time points and by two investigators that were unaware of one another’s measurements and of the study time point, in a group of 30 randomly selected subjects.p < 0.05, exclusion criteria p > 0.10) to obtain the most appropriate theoretical model to fit the collected data. Regression models were built using a training test partition. The training was performed on a randomly selected partition consisting of 80% of our data, while the testing was performed on the remaining 20%. Training and testing of the classifiers were carried out by a repeated 10-fold cross-validation method. To avoid biased predictions, we averaged model performance metrics across test folds. A characteristic (ROC) curve was employed to illustrate the identification ability, and the thresholds to discriminate between future adverse remodelling and normal remodelling were determined by Youden’s index. Data analysis was performed using R: A Language and Environment for Statistical Computing . A value of p under 0.05 was considered to indicate statistically significant differences.Continuous variables were presented as a mean with standard deviation (SD) or as a median with an interquartile range (IQR) and categorical variables, such as frequency and percentages. Considering that the results of the normality test (Shapiro–Wilk) showed a non-Gaussian distribution, we used further nonparametric tests for our analysis. The Wilcoxon test was employed to compare the patient’s initial characteristics and after twelve months. A Kruskal–Wallis test, followed by a post hoc analysis with Mann–Whitney U test characteristics, was conducted with a Bonferroni correction to compare the patients’ characteristics regarding cardiac remodelling. Several multivariate regression models were built using the Akaike criterion to assess the independent factors for cardiac remodelling. In the final regression equations, the predictors were accepted according to a repeated backward-stepwise algorithm (inclusion criteria The patients’ baseline characteristics are presented in p < 0.001) and LV end-diastolic volume (p = 0.033), with both of the values being higher. As far as the right ventricular systolic function is concerned, both the RVFW s’ and TAPSE increased in 6 months .Baseline and follow-up echocardiographic parameters are presented in The results of 2D speckle-tracking echocardiography (STE) at baseline and after 6 months are shown in p = 0.018), and the global longitudinal strain was −15.60%  (p < 0.001).The median LVEF was 46.00% , and the GLS was −13.25%  at baseline. On follow-up, these two parameters significantly increased: the LVEF was 50.00%  (p < 0.001) and LS epi was −13.80  (p < 0.001). Furthermore, we assessed the LS endo/epi ratio, with no significant differences between baseline and follow-up  at admission and 1.30  at follow-up, p = 0.496). On the other hand, there was no difference in the mid-CS endo, mid-CS epi, and mid-CS endo/epi ratio at follow-up , −19.60 ; mid-CS epi: −7.00 , −8.00 ; and mid-CS endo/epi ratio: 2.45 , 2.23 ). On initial evaluation, the longitudinal strain (LS) increased from the epicardial (LS epi) layer to the endocardial (LS endo) layer  and −11.00 , respectively). This pattern was also observed at 6 months when LS endo was −18.10  .In addition, there were greater values at 6 months of the following parameters: base CS, apical CS, and apical RS , −11.70 , and 21.00 , respectively, and −11.40 , −13.20 , and 24.33 , respectively, at 6 months) (2 = 0.611)  .Remodelling was classified as reverse  and adverse , and the patients who did not fit into any category were defined as being normal (no remodelling) .p = 0.035). Moreover, there was no difference regarding the distribution of age, gender, smoking, diabetes mellitus, and obesity among the three groups.The baseline demographic, clinical, and biochemical characteristics of the three STEMI patient groups are compared in The laboratory and angiographic characteristics in cardiac remodelling groups are listed in p < 0.001).The general echocardiographic parameters are listed in p = 0.073 and p = 0.064, respectively). The results are labelled in In terms of speckle-tracking echocardiography, mechanical dispersion and radial strain at the level of papillary muscles (mid-RS) are marginally significant between the adverse and reverse remodelling groups (2 = 0.286). The risk of adverse remodelling increases with age (by 1.1-fold), triglycerides (by 1.009-fold), and mid-RS (1.06-fold). An increased initial twist decreases the chances of adverse remodelling (0.847-fold)  were used in order to determine the best model. The odds ratio and a 95% confidence interval were calculated. Our regression equation proved to be a good fit for the model, explaining 36.2% of the adverse remodelling (R47-fold) .The multivariate logistic regression of independent risk factors for adverse remodelling showed us that the initial value of twist has a high impact when it comes to predicting the adverse remodelling at 6 months. For this reason, we employed a ROC analysis in order to find the threshold point that predicts adverse remodelling .p = 0.04 .Because LVEF does not accurately evaluate intrinsic myocardial deformation, it is possible for it to be normal even when the LV systolic function is compromised. Moreover, in the studied group, the LVEF did not register a statistically significant difference in the adverse remodelling group compared to the reverse one  evaluated by speckle-tracking echocardiography may overcome these restrictions, and it has been proven to be a crucial prognostic parameter in the risk stratification of patients following AMI.p = 0.587)), which are superimposed over the ones in the above studies.Based on previous studies, there is still no consensus on the GLS cut-off value that most accurately predicts mortality and morbidity. Studies have shown that GLS is below 12–15% in most cases. Bendery et al. recently suggested that a baseline GLS score <12.65% was the only significant independent predictor of 30-day MACE, with a sensitivity of 77.8% and a specificity of 83.7% . GuedemaMyocardial injury caused by ischaemia begins from the endocardium and spreads to the myocardium and epicardium as a result of the epicardial location of the coronary arteries and LV systolic pressure gradient during systole, which is called the wave-front phenomenon . TherefoSkaarup et al., in a study that included  465 patiIn agreement with our study, both Hamada et al.  and SkaaSong et al. examined the longitudinal, circumferential, and radial LV strains in a group of patients undergoing PCI after inferior STEMI. Following PCI, they showed a 60% improvement in global longitudinal and circumferential LV stresses and a lower LV strain  compared to healthy controls. In patients with inferior MI, the LV regional strain was impaired in 87% of cases and it improved in 60% of cases following PCI .Lower, in 1669, was the first to describe the twisting motion of the LV as “the wringing of a linen cloth to squeeze out the water” . Over thIt has been reported that acute myocardial ischaemia and infarction are responsible for a decrease in the LV twist that is related to global ventricular function in animals and humans ,17,38. TThe base may rotate less than the apex and may have a reserve to rotate more to compensate, because the LV basal radius is greater than the LV apical radius. Additionally, the basal rotation can be enhanced and the akinetic apical wall abolished by the opposing power. Second, it is well recognised that anterior AMI typically results in the hypercontraction of the LV basal walls. In anterior MI, the normally perfused residual myocardium next to the coronary blockage exhibits compensatory hyperkinesia ,42.Outcomes in management of STEMI have dramatically improved in recent years. This is mainly due to the development of reperfusion therapy and modern pharmacotherapy, such as ACEI/ARB, beta-blockers, and spironolactone. The goal would be to establish an “individual pathogenic profile” and identify specific genetic variation-based therapies. Until novel drug treatment strategies are implemented, we should focus on primary and secondary prevention, and echocardiography is a major tool for early diagnosis . In thisp = 0.04; the Youden index indicates an optimal cut-off value of 11 for the twist. A twist value higher than 11 has a 76.9% specificity and a 72.7% positive predictive value for normal remodelling at 6 months.As mentioned above, it was shown that the initial value of the twist has a high impact on predicting the adverse remodelling at 6 months. For this reason, we employed ROC analysis in order to find the threshold point that predicts adverse remodelling. The AUROC of the twist for adverse remodelling was 0.648; 95%CI , Spinelli et al.  analysedThere was agreement between our results and the results of a study published by Bertini and his colleagues; they studied 66 patients with AMI, in addition to thirty age-matched healthy subjects as a control group. Their aim was to evaluate the impact of AMI on LV rotational. They found that, compared to normal, the LV twist was reduced in all AMI patients . FurtherIn conclusion, our findings support the fact that 2D STE could be used in patients with STEMI who have undergone successful PCI. The LV twist at baseline predicts the occurrence of LV adverse remodelling at the 6-month follow-up. The LV twist cut-off value that was a predictor of worsening in LV function was 11°. Our study suggests that early twist is a widely available and practical parameter in predicting future left ventricular remodelling after an acute coronary event. This result may have important implications in stratifying risk in patients with STEMI. As judicious use of diagnostic and therapeutic modalities may prevent and/or reverse REM and improve quality of life and life span, the LV twist should be considered as a complementary approach in all patients early after MI.The most important limitation of this study is its small sample size. Further investigations are thus required to confirm our findings. This could also be the reason why we did not find any independent risk factor for reverse remodelling. Moreover, we did not assess the left ventricle with other imaging modalities, such as cardiac magnetic resonance imaging. All study subjects averaged six decades in age, and the results may be different from younger or older subjects, because it is known that LV rotational characteristics differ with age. There is a need for further research identifying potential mechanistic pathways and optimal patient selection criteria for available therapies promoting reverse remodelling and myocardial recovery.Future directions should take into consideration the presence of a subendocardial-to-subepicardial gradient in LV mechanics that may provide a useful clinical measure for early recognition of a subclinical state that is likely to progress into either systolic or diastolic heart failure.