Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Cardiovascular multimodality imaging in women: a scientific statement of the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Cardiovascular diseases (CVD) represent an important cause of mortality and morbidity in women. It is now recognized that there are sex differences regarding the prevalence and the clinical significance of the traditional cardiovascular (CV) risk factors as well as the pathology underlying a range of CVDs. Unfortunately, women have been under-represented in most CVD imaging studies and trials regarding diagnosis, prognosis, and therapeutics. There is therefore a clear need for further investigation of how CVD affects women along their life span. Multimodality CV imaging plays a key role in the diagnosis of CVD in women as well as in prognosis, decision-making, and monitoring of therapeutics and interventions. However, multimodality imaging in women requires specific consideration given the differences in CVD between the sexes. These differences relate to physiological changes that only women experience (e.g. pregnancy and menopause) as well as variation in the underlying pathophysiology of CVD and also differences in the prevalence of certain conditions such as connective tissue disorders, Takotsubo, and spontaneous coronary artery dissection, which are all more common in women. This scientific statement on CV multimodality in women, an initiative of the European Association of Cardiovascular Imaging of the European Society of Cardiology, reviews the role of multimodality CV imaging in the diagnosis, management, and risk stratification of CVD, as well as highlights important gaps in our knowledge that require further investigation.

Disparities in Noninvasive Traditional and Advanced Testing for Coronary Artery Disease: Findings from the INCAPS-COVID 2 Study.

The COVID-19 pandemic disrupted the delivery of cardiovascular care, including noninvasive testing protocols and test selection for the evaluation of coronary artery disease (CAD). Trends in test selection in traditional versus advanced noninvasive tests for CAD during the pandemic and in countries of varying income status have not been well studied. The International Atomic Energy Agency conducted a global survey to assess the pandemic-related changes in the practice of cardiovascular diagnostic testing. Site procedural volumes for noninvasive tests to evaluate CAD from March 2019 (prepandemic), April 2020 (onset), and April 2021 (initial recovery) were collected. We considered traditional testing modalities, such as exercise electrocardiography, stress echocardiography, and stress single-photon emission computed tomography, and advanced testing modalities, such as stress cardiac magnetic resonance, coronary computed tomography angiography, and stress positron emission tomography. Survey data were obtained from 669 centers in 107 countries, reporting the performance of 367,933 studies for CAD during the study period. Compared with 2019, traditional tests were performed 14% less frequently (recovery rate 82%) in 2021 versus advanced tests, which were performed 15% more frequently (128% recovery rate). Coronary computed tomography angiography, stress cardiac magnetic resonance, and stress positron emission tomography showed 14%, 25%, and 25% increases in volumes from 2019 to 2021, respectively. The increase in advanced testing was isolated to high- and upper middle-income countries, with 132% recovery in advanced tests by 2021 compared with 55% in lower income nations. The COVID-19 pandemic exacerbated economic disparities in CAD testing practice between wealthy and poorer countries. Greater recovery rates and even new growth were observed for advanced imaging modalities; however, this growth was restricted to wealthy countries. Efforts to reduce practice variations in CAD testing because of economic status are warranted.

Prognostic Role of Early Cardiac Magnetic Resonance in Myocardial Infarction With Nonobstructive Coronary Arteries.

BACKGROUND: Cardiac magnetic resonance (CMR) plays a pivotal diagnostic role in myocardial infarction with nonobstructive coronary arteries (MINOCA). To date, a prognostic stratification of these patients is still lacking. OBJECTIVES: This study aims to assess the prognostic role of CMR in MINOCA. METHODS: The authors assessed 437 MINOCA from January 2017 to October 2021. They excluded acute myocarditis, takotsubo syndromes, cardiomyopathies, and other nonischemic etiologies. Patients were classified into 3 subgroups according to the CMR phenotype: 1) presence of late gadolinium enhancement (LGE) and abnormal mapping (M) values (LGE+/M+); 2) regional ischemic injury with abnormal mapping and no LGE (LGE-/M+); and 3) nonpathological CMRs (LGE-/M-). The primary outcome was the presence of major adverse cardiovascular events (MACE). The mean follow-up was 33.7 ± 12.0 months and CMR was performed on average at 4.8 ± 1.5 days from the acute presentation. RESULTS: The final cohort included 198 MINOCA; 116 (58.6%) comprised the LGE+/M+ group. During follow-up, MACE occurred significantly more frequently in MINOCA LGE+/M+ than in the LGE+/M- and normal-CMR (LGE-/M-) subgroups (20.7% vs 6.7% and 2.7%; P = 0.006). The extension of myocardial damage at CMR was significantly greater in patients who developed MACE. In multivariable Cox regression, %LGE was an independent predictor of MACE (HR: 1.123 [95% CI: 1.064-1.185]; P < 0.001) together with T2 mapping values (HR: 1.190 [95% CI: 1.145-1.237]; P = 0.001). CONCLUSIONS: In MINOCA with early CMR execution, the %LGE and abnormal T2 mapping values were identified as independent predictors of adverse cardiac events at ∼3.0 years of follow-up. These parameters can be considered as high-risk markers in MINOCA.

Imaging patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).

Myocardial infarction with non-obstructive coronary arteries (MINOCA) defines a heterogeneous group of atherosclerotic and non-atherosclerotic conditions, causing myocardial injury in the absence of obstructive coronary artery disease. Unveiling the mechanisms subtended to the acute event is often challenging; a multimodality imaging approach is helpful to aid the diagnosis. Invasive coronary imaging with intravascular ultrasound or optical coherence tomography should be used, when available, during index angiography to detect plaque disruption or spontaneous coronary artery dissection. Cardiovascular magnetic resonance has instead a key role among the non-invasive modalities, allowing the differentiation between MINOCA and its non-ischaemic mimics and providing prognostic information. This educational paper will provide a comprehensive review of the strengths and limitations of each imaging modality in the evaluation of patients with a working diagnosis of MINOCA.

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late­gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

CMR reclassifies the majority of patients with suspected MINOCA and non MINOCA.

AIMS: In ∼5-15% of all cases of acute coronary syndromes (ACS) have unobstructed coronaries on angiography. Cardiac magnetic resonance (CMR) has proven useful to identify in most patients the underlying diagnosis associated with this presentation. However, the role of CMR to reclassify patients from the initial suspected condition has not been clarified. The aim of this study was to assess the proportion of patients with suspected MINOCA, or non-MINOCA, that CMR reclassifies with an alternative diagnosis from the original clinical suspicion. METHODS AND RESULTS: A retrospective cohort of patients in a tertiary cardiology centre was identified from a registry database. Patients who were referred for CMR for investigation of suspected MINOCA, and a diagnosis pre- and post-CMR was recorded to determine the proportion of diagnoses reclassified. A total of 888 patients were identified in the registry. CMR reclassified diagnosis in 78% of patients. Diagnosis of MINOCA was confirmed in only 243 patients (27%), whilst most patients had an alternative diagnosis (73%): myocarditis n = 217 (24%), Takotsubo syndrome n = 115 (13%), cardiomyopathies n = 97 (11%), and normal CMR/non-specific n = 216 (24%). CONCLUSION: In a large single-centre cohort of patients presenting with ACS and unobstructed coronary arteries, most patients had a non-MINOCA diagnosis (73%) (myocarditis, Takotsubo, cardiomyopathies, or normal CMR/non-specific findings), whilst only a minority had confirmed MINOCA (27%). Performing CMR led to reclassifying patients' diagnosis in 78% of cases, thus confirming its important clinical role and underscoring the clinical challenge in diagnosing MINOCA and non MINOCA conditions.

Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology.

Left ventricular (LV) hypertrophy consists in an increased LV wall thickness. LV hypertrophy can be either secondary, in response to pressure or volume overload, or primary, i.e. not explained solely by abnormal loading conditions. Primary LV hypertrophy may be due to gene mutations or to the deposition or storage of abnormal substances in the extracellular spaces or within the cardiomyocytes (more appropriately defined as pseudohypertrophy). LV hypertrophy is often a precursor to subsequent development of heart failure. Cardiovascular imaging plays a key role in the assessment of LV hypertrophy. Echocardiography, the first-line imaging technique, allows a comprehensive assessment of LV systolic and diastolic function. Cardiovascular magnetic resonance provides added value as it measures accurately LV and right ventricular volumes and mass and characterizes myocardial tissue properties, which may provide important clues to the final diagnosis. Additionally, scintigraphy with bone tracers is included in the diagnostic algorithm of cardiac amyloidosis. Once the diagnosis is established, imaging findings may help predict future disease evolution and inform therapy and follow-up. This consensus document by the Heart Failure Association of the European Society of Cardiology provides an overview of the role of different cardiac imaging techniques for the differential diagnosis and management of patients with LV hypertrophy.

The Role of Advanced Cardiovascular Imaging Modalities in Cardio-Oncology: From Early Detection to Unravelling Mechanisms of Cardiotoxicity.

Advances in cancer therapies have led to a global improvement in patient survival rates. Nevertheless, the price to pay is a concomitant increase in cardiovascular (CV) morbidity and mortality in this population. Increased inflammation and disturbances of the immune system are shared by both cancer and CV diseases. Immunological effects of anti-cancer treatments occur with both conventional chemotherapy and, to a greater extent, with novel biological therapies such as immunotherapy. For these reasons, there is growing interest in the immune system and its potential role at the molecular level in determining cardiotoxicity. Early recognition of these detrimental effects could help in identifying patients at risk and improve their oncological management. Non-invasive imaging already plays a key role in evaluating baseline CV risk and in detecting even subclinical cardiac dysfunction during surveillance. The aim of this review is to highlight the role of advanced cardiovascular imaging techniques in the detection and management of cardiovascular complications related to cancer treatment.

"Please keep on beating"-Participation in a Creative Workshop Offers Unexpected Benefits to Women With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TCM) or "broken heart syndrome" is a rare condition that is more common in women than men, particularly those who are postmenopausal. It mimics a myocardial infarction and psychological factors have been implicated in its etiology as well as being consequences of its presentation. As part of a public engagement project we brought together 8 women (of 12 invited) previously diagnosed with TCM to facilitate a discussion, through participation in a creative workshop-based process, about their illness experience, how they made sense of it, and the meaning it had for them in their lives, and to identify areas of unmet need. Through a range of creative activities we identified that participants had high levels of unmet need in terms of information and psychosocial support. All participants enjoyed the creative process and meeting other people with a diagnosis of TCM. The workshop overall was perceived as empowering. Exploring patient narratives during artist-facilitated workshops is one approach for providing the first steps to addressing unmet need, although the importance of ensuring psychological safety cannot be over-stated.

Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.

Importance: The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown. Objective: To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain. Data Sources: PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021. Study Selection: Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included. Data Extraction and Synthesis: This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Main Outcomes and Measures: Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death. Results: A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%. Conclusion and Relevance: In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.

Feasibility of Wave Intensity Analysis from 4D Cardiovascular Magnetic Resonance Imaging Data.

Congenital heart defects (CHD) introduce haemodynamic changes; e.g., bicuspid aortic valve (BAV) presents a turbulent helical flow, which activates aortic pathological processes. Flow quantification is crucial for diagnostics and to plan corrective strategies. Multiple imaging modalities exist, with phase contrast magnetic resonance imaging (PC-MRI) being the current gold standard; however, multiple predetermined site measurements may be required, while 4D MRI allows for measurements of area (A) and velocity (U) in all spatial dimensions, acquiring a single volume and enabling a retrospective analysis at multiple locations. We assessed the feasibility of gathering hemodynamic insight into aortic hemodynamics by means of wave intensity analysis (WIA) derived from 4D MRI. Data were collected in n = 12 BAV patients and n = 7 healthy controls. Following data acquisition, WIA was successfully derived at three planes (ascending, thoracic and descending aorta) in all cases. The values of wave speed were physiological and, while the small sample limited any clinical interpretation of the results, the study shows the possibility of studying wave travel and wave reflection based on 4D MRI. Below, we demonstrate for the first time the feasibility of deriving wave intensity analysis from 4D flow data and open the door to research applications in different cardiovascular scenarios.

Cardiovascular Magnetic Resonance from Fetal to Adult Life-Indications and Challenges: A State-of-the-Art Review.

Cardiovascular magnetic resonance (CMR) imaging offers a comprehensive, non-invasive, and radiation-free imaging modality, which provides a highly accurate and reproducible assessment of cardiac morphology and functions across a wide spectrum of cardiac conditions spanning from fetal to adult life. It minimises risks to the patient, particularly the risks associated with exposure to ionising radiation and the risk of complications from more invasive haemodynamic assessments. CMR utilises high spatial resolution and provides a detailed assessment of intracardiac and extracardiac anatomy, ventricular and valvular function, and flow haemodynamic and tissue characterisation, which aid in the diagnosis, and, hence, with the management of patients with cardiac disease. This article aims to discuss the role of CMR and the indications for its use throughout the different stages of life, from fetal to adult life.

Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

Role of Cardiac Magnetic Resonance Imaging in the Evaluation of MINOCA.

Myocardial infarction with Non Obstructive Coronary Arteries (MINOCA) is defined by patients presenting with signs and symptoms similar to acute myocardial infarction, but are found to have non-obstructive coronary arteries angiography. What was once considered a benign phenomenon, MINOCA has been proven to carry with it significant morbidity and worse mortality when compared to the general population. As the awareness for MINOCA has increased, guidelines have focused on this unique situation. Cardiac magnetic resonance (CMR) has proven to be an essential first step in the diagnosis of patients with suspected MINOCA. CMR has also been shown to be crucial when differentiating between MINOCA like presentations such as myocarditis, takotsubo and other forms of cardiomyopathy. The following review focuses on demographics of patients with MINOCA, their unique clinical presentation as well as the role of CMR in the evaluation of MINOCA.

Myocardial infarction with non-obstructive coronary arteries: Etiology, diagnosis, treatment and prognosis.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is responsible for 10% of myocardial infarctions. Previously, patients were thought to have good prognosis, but evidence-based management and treatment strategies were scarce. Today, researchers and physicians recognize MINOCA as a condition with non-trivial mortality and morbidity. Therapeutic strategies are highly dependent on the underlying disease mechanism in each patient. However, to reach a diagnosis of MINOCA, a multimodal approach is required and, even with an optimal work-up, the cause remains unknown in 8-25% of patients. Research has been growing and position papers from the European Society of Cardiology (ESC) and the American Heart Association/American College of Cardiology have been published, and MINOCA has been included in the more recent ESC guidelines on myocardial infarction. Nonetheless, some clinicians still assume that the absence of coronary obstruction excludes the possibility of acute myocardial infarction. Therefore, in the present paper, we aim to compile and present the available data on the etiology, diagnosis, treatment, and prognosis of MINOCA.