Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Myocarditis: A Narrative Review.

Importance: In the last decade, immune checkpoint inhibitors (ICIs) have been approved for the treatment of many cancer types. Immune checkpoint inhibitor-associated myocarditis has emerged as a significant and potentially fatal adverse effect. Recognizing, diagnosing, and treating ICI-associated myocarditis poses new challenges for the practicing clinician. Here, the current literature on ICI-associated myocarditis is reviewed. Observations: Clinical presentation and cardiac pathological findings are highly variable in patients with ICI-associated myocarditis. Although endomyocardial biopsy is the criterion standard diagnostic test, a combination of clinical suspicion, cardiac biomarkers (specifically troponin), and cardiac imaging, in addition to biopsy, is often needed to support the diagnosis. Importantly, the combination of a cytotoxic T-lymphocyte-associated protein 4 inhibitor with a programmed cell death protein 1 or programmed death-ligand 1 inhibitor increases the risk of developing ICI-associated myocarditis. Conclusion and Relevance: This review aims to provide a standardized diagnostic and therapeutic approach for patients with suspected ICI-associated myocarditis. A complete history of recent cancer treatments and physical examination in combination with cardiac biomarkers, cardiac imaging, and endomyocardial biopsy represent a pragmatic diagnostic approach for most cases of ICI-associated myocarditis. The addition of novel biomarkers or imaging modalities is an area of active research and should be evaluated in larger cohorts.

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2020: positron emission tomography, computed tomography, and magnetic resonance.

Although the year 2020 was different from other years in many respects, the Journal of Nuclear Cardiology published excellent articles pertaining to imaging in patients with cardiovascular disease due to the dedication of the investigators in our field all over the world. In this review, we will summarize a selection of these articles to provide a concise review of the main advancements that have recently occurred in the field and provide the reader with an opportunity to review a wide selection of articles. We will focus on publications dealing with positron emission tomography, computed tomography, and magnetic resonance and hope that you will find this review helpful.

Appropriate use criteria for cardiovascular magnetic resonance imaging (CMR): SIC-SIRM position paper part 1 (ischemic and congenital heart diseases, cardio-oncology, cardiac masses and heart transplant).

Cardiac magnetic resonance (CMR) has emerged as new mainstream technique for the evaluation of patients with cardiac diseases, providing unique information to support clinical decision-making. This document has been developed by a joined group of experts of the Italian Society of Cardiology and Italian society of Radiology and aims to produce an updated consensus statement about the current state of technology and clinical applications of CMR. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac radiology. Part 1 of the document will cover ischemic heart disease, congenital heart disease, cardio-oncology, cardiac masses and heart transplant.

Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis.

BACKGROUND: The 2017 European Society of Cardiology guidelines for valvular heart disease included changes in the definition of severe aortic stenosis (AS). We wanted to evaluate its influence on management decisions in asymptomatic patients with moderate-severe AS. METHODS: We reclassified the AS severity of the participants of the PRIMID-AS study (Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With AS), using the 2017 guidelines, determined their risk of reaching a clinical end point (valve replacement for symptoms, hospitalization, or cardiovascular death) and evaluated the prognostic value of aortic valve calcium score and biomarkers. Patients underwent echocardiography, cardiac magnetic resonance imaging, exercise tolerance testing, and biomarker assessment. RESULTS: Of the 174 participants, 45% (56/124) classified as severe AS were reclassified as moderate AS. This reclassified group was similar to the original moderate group in clinical characteristics, gradients, calcium scores, and remodeling parameters. There were 47 primary end points (41 valve replacement, 1 death, and 5 hospitalizations-1 chest pain, 2 dyspnea, 1 heart failure, and 1 syncope) over 368±156 days follow-up. The severe and reclassified groups had a higher risk compared with moderate group (adjusted hazard ratio 4.95 [2.02-12.13] and 2.78 [1.07-7.22], respectively), with the reclassified group demonstrating an intermediate risk. A mean pressure gradient ≥31 mm Hg had a 7× higher risk of the primary end point in the reclassified group. Aortic valve calcium score was more prognostic in females and low valve area but not after adjusting for gradients. NT-proBNP (N-terminal pro-brain-type natriuretic peptide) and myocardial perfusion reserve were associated with the primary end point but not after adjusting for positive exercise tolerance testing. Troponin was associated with cardiovascular death or unplanned hospitalizations. CONCLUSIONS: Reclassification of asymptomatic severe AS into moderate AS was common using the European Society of Cardiology 2017 guidelines. This group had an intermediate risk of reaching the primary end point. Exercise testing, multimodality imaging, and lower mean pressure gradient threshold of 31 mm Hg may improve risk stratification. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01658345.

2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. Methods A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Structure Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.

Management of nonischemic-dilated cardiomyopathies in clinical practice: a position paper of the working group on myocardial and pericardial diseases of Italian Society of Cardiology.

: Nonischemic-dilated cardiomyopathy (NIDCM) is an entity that gathers extremely heterogeneous diseases. This awareness, although leading to continuous improvement in survival, has increased the complexity of NIDCM patients' management. Even though the endorsed 'red-flags' approach helps clinicians in pursuing an accurate etiological definition in clinical practice, it is not clear when and how peripheral centers should interact with referral centers with specific expertise in challenging scenarios (e.g. postmyocarditis and genetically determined dilated cardiomyopathy) and with easier access to second-line diagnostic tools and therapies. This position paper will summarize each step in NIDCM management, highlighting the multiple interactions between peripheral and referral centers, from first-line diagnostic workup and therapy to advanced heart failure management and long-term follow-up.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-Diagnostic criteria and appropriate utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

Practical implementation of the Endocarditis Team in 'functional' reference centres: the Italian hospital network experience and recommendations of the Italian Society of Echocardiography and Cardiovascular Imaging.

: The 2015 European Society of Cardiology (ESC) guidelines for the management of infective endocarditis recommend the use of a multidisciplinary team in the care of patients with infective endocarditis. A standardized collaborative approach should be implemented in centres with immediate access to different imaging techniques, cardiac surgery and health professionals from several specialties. This position paper has been produced by the Task Force for Management of Infective Endocarditis of Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) with the aim of providing recommendations for the implementation of the Endocarditis Team within the Italian hospital network. On the basis of the Italian hospital network with many cardiology facilities encompassing a total of 405 intensive cardiac care units (ICCUs) across the country, 224 (3.68 per million inhabitants) of which have on-site 24-h PCI capability, but with relatively few centres equipped with cardiac surgery and nuclear medicine, in the present article, the SIECVI Task Force for Management of Infective Endocarditis develops the idea of a network where 'functional' reference centres act as a link with the periphery and with 'structural' reference centres. A number of minimum characteristics are provided for these 'functional' reference centres. Outcome and cost analysis of implementing an Endocarditis Team with functional referral is expected to be derived from ongoing Italian and European registries.

The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti-hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo-controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions.

The Current Role of Viability Imaging to Guide Revascularization and Therapy Decisions in Patients With Heart Failure and Reduced Left Ventricular Function.

This review describes the current evidence and controversies for viability imaging to direct revascularization decisions and the impact on patient outcomes. Balancing procedural risks and possible benefit from revascularization is a key question in patients with heart failure of ischemic origin (IHF). Different stages of ischemia induce adaptive changes in myocardial metabolism and function. Viable but dysfunctional myocardium has the potential to recover after restoring blood flow. Modern imaging techniques demonstrate different aspects of viable myocardium; perfusion (single-photon emission computed tomography [SPECT], positron emission tomography [PET], cardiovascular magnetic resonance [CMR]), cell metabolism (PET), cell membrane integrity and mitochondrial function (201Tl and 99mTc-based SPECT), contractile reserve (stress echocardiography, CMR) and scar (CMR). Observational studies suggest that patients with IHF and significant viable myocardium may benefit from revascularization compared with medical treatment alone but that in patients without significant viability, revascularization appears to offer no survival benefit or could even worsen the outcome. This was not supported by 2 randomized trials (Surgical Treatment for Ischemic Heart Failure [STICH] and PET and Recovery Following Revascularization [PARR] -2) although post-hoc analyses suggest that benefit can be achieved if decisions had been strictly based on viability imaging recommendations. Based on current evidence, viability testing should not be the routine for all patients with IHF considered for revascularization but rather integrated with clinical data to guide decisions on revascularization of high-risk patients with comorbidities.

Global vascular guidelines on the management of chronic limb-threatening ischemia.

Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

The use of handheld ultrasound devices: a position statement of the European Association of Cardiovascular Imaging (2018 update).

Recent technological advances in echocardiography, with progressive miniaturization of ultrasound machines, have led to the development of handheld ultrasound devices (HUD). These devices, no larger than some mobile phones, can be used to perform partial, focused exams as an extension to the physical examination. The European Association of Cardiovascular Imaging (EACVI) acknowledges that the dissemination of appropriate HUD use is inevitable and desirable, because of its potential impact on patient management. However, as a scientific society of cardiac imaging, our role is to provide guidance in order to optimize patient benefit and minimize drawbacks from inappropriate use of this technology. This document provides updated recommendations for the use of HUD, including nomenclature, appropriateness, indications, operators, clinical environments, data management and storage, educational needs, and training of potential users. It also addresses gaps in evidence, controversial issues, and future technological developments.

Learning-Based Quality Control for Cardiac MR Images.

The effectiveness of a cardiovascular magnetic resonance (CMR) scan depends on the ability of the operator to correctly tune the acquisition parameters to the subject being scanned and on the potential occurrence of imaging artifacts, such as cardiac and respiratory motion. In the clinical practice, a quality control step is performed by visual assessment of the acquired images; however, this procedure is strongly operator-dependent, cumbersome, and sometimes incompatible with the time constraints in clinical settings and large-scale studies. We propose a fast, fully automated, and learning-based quality control pipeline for CMR images, specifically for short-axis image stacks. Our pipeline performs three important quality checks: 1) heart coverage estimation; 2) inter-slice motion detection; 3) image contrast estimation in the cardiac region. The pipeline uses a hybrid decision forest method-integrating both regression and structured classification models-to extract landmarks and probabilistic segmentation maps from both long- and short-axis images as a basis to perform the quality checks. The technique was tested on up to 3000 cases from the UK Biobank and on 100 cases from the UK Digital Heart Project and validated against manual annotations and visual inspections performed by expert interpreters. The results show the capability of the proposed pipeline to correctly detect incomplete or corrupted scans (e.g., on UK Biobank, sensitivity and specificity, respectively, 88% and 99% for heart coverage estimation and 85% and 95% for motion detection), allowing their exclusion from the analyzed dataset or the triggering of a new acquisition.

Native T1 and Extracellular Volume Measurements by Cardiac MRI in Healthy Adults: A Meta-Analysis.

Purpose To summarize the literature by performing a systematic review and pooled analysis of the data, to understand the extent of variability among studies of native T1 and extracellular volume (ECV) measurements, and to identify covariates that account for heterogeneity between studies. Materials and Methods PubMed, Web of Science, and Cochrane Central were searched for native T1 and ECV measurements of the left ventricle in health adult study participants. The search terms used were "T1 mapping heart," "Native T1 heart," and "ECV heart." Summary means were generated with random-effects modeling. Heterogeneity was assessed by using the inconsistency factor (I 2). Subgroup analyses and meta-regression analyses were conducted to identify etiologic causes of heterogeneity. Results This systematic review of native T1 included 120 articles, with 5541 participants (mean age, 50 years; 51.0% men [2826 of 5541]). The pooled mean of native T1 was 976 msec (95% confidence interval [CI]: 969 msec, 983 msec) at 1.5 T and 1159 msec (95% CI: 1143 msec, 1175 msec) at 3.0 T. I 2 was 99% at both field strengths. Eighty-one articles were included in the systematic review of ECV, with 3872 participants (mean age, 52 years; 50.0% men [1936 of 3872]). The pooled mean of ECV was 25.9% at field strength of 1.5 T (95% CI: 25.5%, 26.3%) and 3.0 T (95% CI: 25.4%, 26.5%). I 2 was 94% and 90% at 1.5 and 3.0 T, respectively. Conclusion The pooled means of extracellular volume and native T1 measurements in healthy adult participants are summarized in this analysis. There was significant heterogeneity found among studies, highlighting the importance of standardized cardiac MRI protocols and the derivation of institution specific reference ranges. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Dodd and Dewey in this issue.