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Objectives: The purpose of this study was to assess the diagnostic accuracy of blood oxygen-level dependent (BOLD) MRI in suspected coronary artery disease (CAD).Background: By exploiting the paramagnetic properties of deoxyhemoglobin, BOLD magnetic resonance imaging can detect myocardial ischemia. We applied BOLD imaging and first-pass perfusion techniques to: 1) examine the pathophysiological relationship between coronary stenosis, perfusion, ventricular scar, and myocardial oxygenation; and 2) evaluate the diagnostic performance of BOLD imaging in the clinical setting.Methods: BOLD and first-pass perfusion images were acquired at rest and stress (4 to 5 min intravenous adenosine, 140 μg/kg/min) and assessed quantitatively (using a BOLD signal intensity index [stress/resting signal intensity], and absolute quantification of perfusion by model-independent deconvolution). A BOLD signal intensity index threshold to identify ischemic myocardium was first determined in a derivation arm (25 CAD patients and 20 healthy volunteers). To determine diagnostic performance, this was then applied in a separate group comprising 60 patients with suspected CAD referred for diagnostic angiography.Results: Prospective evaluation of BOLD imaging yielded an accuracy of 84%, a sensitivity of 92%, and a specificity of 72% for detecting myocardial ischemia and 86%, 92%, and 72%, respectively, for identifying significant coronary stenosis. Segment-based analysis revealed evidence of dissociation between oxygenation and perfusion (r = -0.26), with a weaker correlation of quantitative coronary angiography with myocardial oxygenation (r = -0.20) than with perfusion (r = -0.40; p = 0.005 for difference). Hypertension increased the odds of an abnormal BOLD response, but diabetes mellitus, hypercholesterolemia, and the presence of ventricular scar were not associated with significant deoxygenation.Conclusions: BOLD imaging provides valuable insights into the pathophysiology of CAD; myocardial hypoperfusion is not necessarily commensurate with deoxygenation. In the clinical setting, BOLD imaging achieves favorable accuracy for identifying the anatomic and functional significance of CAD. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate whether positron emission tomography/computed tomography (CT) angiography using [11C]-PK11195, a selective ligand for peripheral benzodiazepine receptors expressed in activated macrophages, can be used to image vascular inflammation. Background: Activated macrophages and T lymphocytes are fundamental elements in the pathogenesis of large-vessel vasculitides. Methods: Fifteen patients (age 52+/-16 years) with systemic inflammatory disorders (6 consecutive symptomatic patients with clinical suspicion of active vasculitis and 9 asymptomatic control patients) underwent positron emission tomography with [11C]-PK11195 and CT angiography. [11C]-PK11195 uptake was measured by calculating target-to-background ratios of activity normalized to venous blood. Results: Coregistration of positron emission tomography with contrast-enhanced CT angiography facilitated localization of [11C]-PK11195 arterial wall uptake. Visual analysis revealed focal [11C]-PK11195 uptake in the arterial wall of all 6 symptomatic patients, but in none of the asymptomatic controls. Although serum inflammatory biomarkers (C-reactive protein, erythrocyte sedimentation rate, white cell count) did not differ significantly between the 2 groups, symptomatic patients had increased [11C]-PK11195 vascular uptake (target-to-background ratio 2.41+/-1.59 vs. 0.98+/-0.10; p=0.001). Conclusions: By binding to activated macrophages in the vessel wall, [11C]-PK11195 enables noninvasive imaging of vascular inflammation. Alternative longer-lived radioligands for probing peripheral benzodiazepine receptors are being tested for wider clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: This study's aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).Background: Thiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.Methods: We undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.Results: Whereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 +/- 1.59 mg/kg/min to 5.24 +/- 1.65 mg/kg/min; p = 0.004) and MGU (0.62 +/- 0.26 micromol/g/min to 0.81 +/- 0.14 micromol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 +/- 0.20 ml/min/g to 1.25 +/- 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced.Conclusions: In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659). [ABSTRACT FROM AUTHOR]

Compared to normal volunteers, coronary vasodilation reserve is reduced in patients with hypertrophic cardiomyopathy but not in rowing athletes with left ventricular hypertrophy. Positron emission tomography can provide complementary information to distinguish between the athlete's heart and hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Formal assessment of myocardial viability (MV) is challenging in acute myocardial infarction-related cardiogenic shock (AMI-CS) patients receiving Impella mechanical circulatory support, as the cardiac magnetic resonance gold standard technique is not feasible due to the metallic components of the device. 18-fluorodesoxyglucose metabolic myocardial positron emission tomography ( 18 FDG-PET) may represent a valid and feasible alternative to obtain semi-quantitative and objective evidence of MV during Impella support. We hereby report the first series of sequential AMI-CS patients who received 18 FDG-PET scanning to assess MV during Impella support to demonstrate the safety and feasibility of this approach. In this cohort no adverse events occurred during 18 FDG-PET scans, and all images were of excellent quality. This study provides a pragmatic guidance on how to perform this imaging modality during Impella support and finally confirms the safety and feasibility of this advanced imaging method also in this vulnerable cohort of patients., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Identifying markers associated with adverse events after acute myocarditis (AM) is relevant to plan follow-up. We assessed the prognostic performance of previously described cardiac magnetic resonance imaging (CMRI) markers and their combination: septal late gadolinium enhancement (LGE) localization and left ventricular ejection fraction (LVEF) < 50 % on baseline CMRI versus complicated clinical presentation (CCP: the presence of sustained ventricular tachycardia, or LVEF<50 % on the first echocardiogram or fulminant presentation)., Methods: We retrospectively assessed 248 AM patients (median age of 34 years, 87.1 % male) from 6 hospitals with onset of cardiac symptoms<30 days, increased troponin, and CMRI/histology consistent with myocarditis to identify those at risk of major cardiac events (cardiac death, heart transplantation, aborted sudden cardiac death, sustained ventricular tachycardia, or heart failure hospitalization)., Results: Thirteen patients (5.2 %) experienced at least one major cardiac event after a median follow-up of 4.7 years with a significant hazard ratio of 35.8 for CCP vs. 9.2 for septal LGE vs. 12.4 for LVEF<50 % on baseline CMRI (p = 0.001). CCP had the best c-index to identify patients with events: 0.836 vs. 0.786 for septal LGE and 0.762 for LVEF<50 %, while the combination of CCP plus LVEF<50 % or septal LGE has the highest c-index of 0.866. All 3 markers had high negative predictive value (NPV) of ≥0.98., Conclusions: Major cardiac events after an AM are relatively low, and CCP, septal LGE, and LVEF<50 % are significantly associated with events. These markers have especially high NPV to identify patients without events after an AM. These observations can help clinicians to monitor the patients after an AM., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: Conflict of interest: E.A. received a grant from the Italian Ministry of Health [GR-2019-12368506; principal investigator of the investigator-driven MYTHS (Myocarditis Therapy with Steroids) trial] and a grant from the Italian Ministry of Health and NextGenerationEU (PNRR-MAD-2022-12376225) and received consultation fees for Kiniksa, Cytokinetics, and AstraZeneca.

Background: Clinical evaluation of central venous pressure is difficult, depends on experience, and is often inaccurate in patients with chronic advanced heart failure. We assessed the ultrasound-assessed internal jugular vein (JV) distensibility by ultrasound as a noninvasive tool to identify patients with normal right atrial pressure (RAP ≤7 mm Hg) in this population., Methods: We measured JV distensibility as the Valsalva-to-rest ratio of the vein diameter in a calibration cohort (N=100) and a validation cohort (N=101) of consecutive patients with chronic heart failure with reduced ejection fraction who underwent pulmonary artery catheterization for advanced heart failure therapies workup., Results: A JV distensibility threshold of 1.6 was identified as the most accurate to discriminate between patients with RAP ≤7 versus >7 mm Hg (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.64-0.84]) and confirmed in the validation cohort (receiver operating characteristic, 0.82 [95% CI, 0.73-0.92]). A JV distensibility ratio >1.6 had predictive positive values of 0.86 and 0.94, respectively, to identify patients with RAP ≤7 mm Hg in the calibration and validation cohorts. Compared with patients from the calibration cohort with a high JV distensibility ratio (>1.6; n=42; median RAP, 4 mm Hg; pulmonary capillary wedge pressure, 11 mm Hg), those with a low JV distensibility ratio (≤1.6; n=58; median RAP, 8 mm Hg; pulmonary capillary wedge pressure, 22 mm Hg; P <0.0001 for both) were more likely to die or undergo a left ventricular assist device implant or heart transplantation (event rate at 2 years: 42.7% versus 18.2%; log-rank P =0.034)., Conclusions: Ultrasound-assessed JV distensibility identifies patients with chronic advanced heart failure with normal RAP and better outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03874312., Competing Interests: Disclosures The authors disclose that Dr Ammirati received a grant from the Italian Ministry of Health (GR-2019-12368506) and a grant from the NextGenerationEU (M6C2/2.1 PNRR-MAD-2022-12376225—CUP H43C21000140006) and served as a consultant for Kiniksa Pharmaceuticals, Cytokinetics, and AstraZeneca. Dr Pellicori has received consultancy honoraria and sponsorship support from Boehringer Ingelheim, Pharmacosmos, Novartis, Vifor, AstraZeneca, and Caption Health and research support from Bristol Myers Squibb in the past 5 years, not connected with this article. Prof Metra is the outgoing Editor-in-Chief of the European Journal of Heart Failure. The other authors report no conflicts.

Objectives: To ascertain whether invasive assessment of coronary physiology soon after recanalisation of the culprit artery by primary percutaneous coronary intervention is associated with the development of microvascular obstruction by cardiac magnetic resonance in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: Between November 2020 and December 2021, 102 consecutive patients were prospectively enrolled in five tertiary centres in Italy. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the culprit vessel soon after successful primary percutaneous coronary intervention. Optimal cut-off points of IMR and CFR to predict the presence of microvascular obstruction were estimated, stratifying the population accordingly in four groups. A comparison with previously proposed stratification models was carried out., Results: IMR > 31 units and CFR≤1.25 yielded the best accuracy. Patients with IMR>31 and CFR≤1.25 exhibited higher microvascular obstruction prevalence (83% vs 38%, p<0.001) and lower left ventricular ejection fraction (45±9% vs 52±9%, p=0.043) compared with those with IMR≤31 and CFR>1.25, and lower left ventricular ejection fraction compared with patients with CFR≤1.25 and IMR≤31 (45±9% vs 54±7%, p=0.025). Infarct size and area at risk were larger in the former, compared with other groups., Conclusions: IMR and CFR are associated with the presence of microvascular obstruction in STEMI. Patients with an IMR>31 units and a CFR≤1.25 have higher prevalence of microvascular obstruction, lower left ventricular ejection fraction, larger infarct size and area at risk., Trial Registration Number: NCT04677257., Competing Interests: Competing interests: SB, GC, RAM, RR, GM, MG, AE, AP, DT, AB and PGC has no interests to disclose. MM reports consultant or speaker fees from Abbott, Boston, Kardia, Medtronic, not related to this work. MA reports consultant or speaker fees from Abbott, Abiomed, not related to this work. IP reports consultant or speaker fees from Biotronik, ABIOMED, Terumo, Philips, Sanofi, Amgen, Daiichi-Sankyo, Astra Zeneca, Bayer and PIAM, not related to this work. GA reports consultant or speaker fees from Amarin, Behring, CLS, Menarini, Novartis, not related to this work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Clinical features and risk stratification of patients with viral myocarditis (VM) complicated by ventricular arrhythmias (VA) are incompletely understood. We aim to describe arrhythmia patterns and outcomes in patients with VM and early-onset VA., Methods and Results: We present a single-centre study, enrolling patients with VM proven by endomyocardial biopsy, and evidence of VA within 24 h of hospitalization. The incidence of major adverse events (MAE), including all-cause death, severe heart failure, advanced atrioventricular blocks, or major VA, was evaluated during a 24-month follow-up (FU) and compared with a matched group of virus-negative myocarditis. Of patients with VM ( n = 74, mean age 47 ± 16 years, 66% males, and left ventricular ejection fraction 51 ± 13%), 20 (27%) presented with major VA [ventricular tachycardia/ventricular fibrillation (VT/VF)], and 32 (44%) had polymorphic VA. Patients with polymorphic VA more commonly had evidence of ongoing systemic infection (24/32 vs. 10/42, P = 0.004) and experienced greater occurrence of MAE at discharge (15/32 vs. 2/42, P < 0.001). However, the incidence of MAE during FU was higher in patients with monomorphic VA compared to those with polymorphic VA (17/42 vs. 2/28, P = 0.002). Patients with monomorphic VA displayed frequently signs of chronic cardiomyopathy and had outcomes comparable with virus-negative myocarditis (log rank P = 0.929). Presentation with VT/VF was independently associated with MAE [at discharge: hazard ratio (HR) 4.7, 95% confidence interval (CI) 1.6-14.0, P = 0.005; during FU: HR 6.3, 95% CI 2.3-17.6, P < 0.001]., Conclusion: In patients with VM, polymorphic VA point to ongoing systemic infection and early adverse outcomes, whereas monomorphic VA suggest chronic cardiomyopathy and greater incidence of MAE during FU. Presentation with VT/VF is independently associated with MAE., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Women with obstructive coronary artery disease (CAD) have a relatively lower quality of life (QoL) compared to men, but our understanding of sex differences in QoL in ischemia with no obstructive coronary artery disease (INOCA) is limited. We conducted a survey of patient members of INOCA International with an assessment of self-reported health measures. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed before and after INOCA symptom onset. Of the 1579 patient members, the overall survey completion rate was 21%. Women represented 91% of the respondents. Estimated functional capacity, expressed as metabolic equivalents (METs), was higher before compared to after INOCA diagnosis comparably for both women and men. For every one MET decline in functional capacity, there was a significantly greater decline in QoL for men compared with women in physical health (4.0 ± 1.1 vs. 2.9 ± 0.3 days/month, p < 0.001), mental health (2.4 ± 1.2 vs. 1.8 ± 0.3 days/month, p = 0.001), and social health/recreational activities (4.1 ± 1.0 vs. 2.9 ± 0.3 days/month, p = 0.0001), respectively. In an international survey of patients living with INOCA, despite similar diagnoses, clinical comorbidities, and symptoms, INOCA-related functional capacity declines are associated with a greater adverse impact on QoL in men compared to women.

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into "classical" (predominantly related to hyperemic MBFs) and "endogen" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials., Competing Interests: Funding Support and Author Disclosures Dr Schindler has received institutional research grant support from GE Healthcare and National Institutes of Health/NHLBI (1RO1HL142297-01A1). Dr Fearon has received institutional research grant support from Abbott, Boston Scientific, and Medtronic; consulting fees from CathWorks and Siemens; and stock options from HeartFlow. Dr Pelletier-Galarneau is supported by a Junior 1 Research Award from the Fonds de Recherche du Québec–Santé (FRQS), and he has received consultant fees and research funds from Jubilant Radiopharma. Dr Bhatt has served on the advisory boards of AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the board of directors for AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; has served as chair for the American Heart Association Quality Oversight Committee (Inaugural Chair); consultant for Broadview Ventures; and on data-monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo, and for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT trial); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute); RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary-Treasurer), WebMD (CME steering committees), Wiley (steering committee); has served as Deputy Editor for Clinical Cardiology, Chair for NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; he has received a patent for sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither he nor Brigham and Women's Hospital have received income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; and royalties from Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; and unfunded research for FlowCo and Takeda. Dr Ruddy has received institutional research grant support from GE Healthcare and Advanced Accelerator Applications International. Dr Bateman has received institutional research grant support from Bracco, GEHC, and Spectrum Dynamics; has served as consultant for GEHC and has received royalties from SPECT and PET software products and equity interest from CVIT. Dr Knuuti has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer, and Merck, outside of the submitted work. Dr Slart has received institutional research grant support from Pfizer and Siemens Healthineers. Dr Windecker has received research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an unpaid advisory board member or unpaid member of the steering-executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers; and is also a member of the steering-executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Taqueti has received research support from National Institutes of Health K23HL135438. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is limited information available regarding evidence of ischemia with no obstructive coronary arteries (INOCA) and quality of life., Purpose: To determine associations between INOCA and self-reported physical, social, and mental health., Methods: We conducted a survey of all members (n = 1579) of the INOCA International patient support group. Current self-reported diagnosis and health measures were collected. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed prior and after symptom onset., Results: A total of 297 (20.8% response rate, 91% women) reported symptoms of chest pain, pressure, or discomfort in 92.9%. Overall, 34.4% were living with symptoms for ≥3 years before an INOCA diagnosis, and 77.8% were told their symptoms were not cardiac. Estimated functional capacity was higher prior to compared to after symptom onset (8.6 ± 1.8 METs vs 5.6 ± 1.8 METs; P < 0.0001). Most respondents reported an adverse impact of symptoms on their home life (80.5%), social life (80.1%), mental health (70.4%), outlook on life (69.7%), sex life (55.9%), and their partner/spouse relationship (53.9%), while approximately three-quarters reduced their work hours or stopped work completely, 47.5% retired early, and 38.4% applied for disability., Conclusions: INOCA symptoms are associated with adverse physical, mental and social health quality of life. Increased patient awareness, physician recognition and diagnosis, and clinical trials are needed to develop evidence-based guidelines for this increasingly recognized cardiovascular disorder., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI., Methods and Results: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REM EDV )]; LV-REM by end-systolic volume index increase ≥12% (LV-REM ESV ) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REM EDV and LV-REM ESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REM EDV , whilst it decreased in those with LV-REM ESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REM EDV , the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF., Conclusions: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REM EDV was lower than previously reported. Importantly, our data indicate that LV-REM EDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REM ESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Myocardial ischemia is an established pathophysiological feature of hypertrophic cardiomyopathy (HCM) that impacts various clinical features, including heart failure (HF) and sudden cardiac death (SCD). The major determinant of myocardial ischemia in HCM is coronary microvascular dysfunction (CMD) in the absence of epicardial coronary artery abnormalities. Despite the impossibility to directly visualize microcirculation in vivo, a multimodality approach can allow a detailed assessment of microvascular dysfunction and ischemia. Accordingly, the non-invasive assessment of CMD using transthoracic Doppler echocardiography, positron emission tomography, and cardiac magnetic resonance should now be considered mandatory in any HCM patient. Noteworthy, a complete diagnostic work-up for myocardial ischemia plays a major role in the approach of the patients with HCM and their risk stratification. Chronic and recurrent episodes of ischemia can contribute to fibrosis, culminating in LV remodeling and HF. Ischemia can potentially constitute an arrhythmic substrate and might prove to have an added value in risk stratification for SCD. Accordingly, strategies for the early diagnosis of CMD should now be considered an important challenge for the scientific community.

Objective: Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM., Methods: Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile., Results: We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls., Conclusions: We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

BackgroudThe aim of this study was to assess the prognostic association of plasma levels of N -terminal prohormone of brain natriuretic peptide (NT-proBNP) with clinical outcomes of patients with microvascular angina (MVA)., Methods: In this international prospective cohort study of MVA by the Coronary Vasomotor Disorders International Study (COVADIS) group, we examined the association between plasma NT-proBNP levels and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina., Results: We examined a total of 226 MVA patients (M/F 66/160, 61.9 ± 10.2 [SD] yrs.) with both plasma NT-proBNP levels and echocardiography data available at the time of enrolment. The median level of NT-proBNP level was 94 pg/ml, while mean left ventricular ejection fraction was 69.2 ± 10.9 % and E/e' 10.7 ± 5.2. During follow-up period of a median of 365 days (IQR 365-482), 29 MACEs occurred. Receiver-operating characteristics curve analysis identified plasma NT-proBNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-proBNP level ≥ 78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95 % confidence interval (CI)] 3.11[1.14-8.49], P = 0.001). Accordingly, Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-proBNP ≥ 78 (log-rank test, P < 0.03). Finally, a significant positive correlation was observed between plasma NT-proBNP levels and E/e' (R = 0.445, P < 0.0001)., Conclusions: These results indicate that plasma NT-proBNP levels may represent a novel prognostic biomarker for MVA patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown., Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV., Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up., Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P &lt; 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM., Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk., Competing Interests: Funding Support and Author Disclosures Dr Ammirati has received a grant from the Italian Ministry of Health (GR-2019-12368506) and is a consultant for Kiniksa and Cytokinetics. Dr Adler is a consultant for Abbott, Abiomed, AstraZeneca, Endotronix, Ionis, Medtronic, and Novartis; is on the board of directors of Genstem Therapeutics; and is a shareholder of Rocket Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes ( MYH7 , MYH7B and MYLC2 ), and the MyomiR network (myosin-encoded microRNA ( miRs ) and long-noncoding RNAs ( Mhrt )) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B , and MYLC2 were higher in HCM whilst MYH6 , miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499 -target genes, SOX6 and PTBP3 , were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499 , demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets., Competing Interests: The authors declare no conflict of interest.

Background: Among the other variants, the apical pattern of hypertrophic cardiomyopathy (AHCM) is probably the most important, with possible aneurysmatic evolution., Methods and Results: We analyzed 12 patients with AHCM who underwent [ 13 N]NH 3 -PET/CT. Regional perfusion, stress global myocardial blood flow (MBF), and transmural perfusion patterns were assessed. To evaluate the LV-MBF distribution, we compared the apex with septum and infero-lateral wall. Furthermore, global stress MBF distribution in AHCM patients was compared with a reference septal HCM cohort. Visual regional perfusion analysis demonstrated an apical hypoperfusion in 10 of 12 patients, without correlation with the stress MBF of the whole LV. Significant differences among stress MBF in apical, in septal, and in the infero-lateral walls were recorded (P < .02). The transmural analysis showed a significant difference among the three segment groups for epicardial (P < .003) as well for endocardial MBF (P < .005). In the post hoc analysis, the apical MBF was significantly lower than in septal and infero-lateral walls in epicardium (P < .005) and significantly lower than the infero-lateral MBF in endocardium (P < .001)., Conclusion: In patients with AHCM, more severe apical microvascular impairment was found as compared to patients with classical septal HCM, supporting the suspicion that ischemia could play a role in the future aneurysmatic evolution of AHCM., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe., Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM., Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P <0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%)., Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Aims: Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy., Methods and Results: Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P<0.001). Group 3 showed significantly higher values of all Dfs compared to the other Groups. Both basal and total Dfs were significantly higher in Group 1 compared with controls (basal: 1.30±0.03 vs. 1.26±0.04, P =0.010; total: 1.29±0.02 vs. 1.27±0.02, P=0.044). Total Df showed significant correlations with: (i) T1 value (r=-0.569; P<0.001); (ii) LV mass (r=0.664, P<0.001); (iii) trabecular mass (r=0.676; P <0.001); (iv) Mainz Severity Score Index (r=0.638; P<0.001)., Conclusion: Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)