Sharmila Dorbala MD, MPH, MASNC , Rosalyn Adigun MD, PharmD, MS , Kevin M. Alexander MD , Michela Brambatti MD, MS , Sarah A.M. Cuddy MB, Bch, BAO , Angela Dispenzieri MD , Preston Dunnmon MD, MBA , Michele Emdin MD, PhD , Omar F. Abou Ezzeddine MD, CM, MS , Rodney H. Falk MD , Mariana Fontana MD, PhD , Justin L. Grodin MD, MPH , Spencer Guthrie MPH, MBA , Michael Jerosch-Herold PhD , A. Alex Hofling MD, PhD , Kristen Hsu BS , Grace Lin MD, MBA , Ahmad Masri MD, MS , Mathew S. Maurer MD , Clemens Mittmann MD , Isabelle Lousada MA
{"title":"Development of Imaging Endpoints for Clinical Trials in AL and ATTR Amyloidosis","authors":"Sharmila Dorbala MD, MPH, MASNC , Rosalyn Adigun MD, PharmD, MS , Kevin M. Alexander MD , Michela Brambatti MD, MS , Sarah A.M. Cuddy MB, Bch, BAO , Angela Dispenzieri MD , Preston Dunnmon MD, MBA , Michele Emdin MD, PhD , Omar F. Abou Ezzeddine MD, CM, MS , Rodney H. Falk MD , Mariana Fontana MD, PhD , Justin L. Grodin MD, MPH , Spencer Guthrie MPH, MBA , Michael Jerosch-Herold PhD , A. Alex Hofling MD, PhD , Kristen Hsu BS , Grace Lin MD, MBA , Ahmad Masri MD, MS , Mathew S. Maurer MD , Clemens Mittmann MD , Isabelle Lousada MA","doi":"10.1016/j.jcmg.2024.11.003","DOIUrl":"10.1016/j.jcmg.2024.11.003","url":null,"abstract":"<div><div>Light chain amyloidosis and transthyretin amyloidosis are rare protein misfolding disorders characterized by amyloid deposition in organs, varied clinical manifestations, and poor outcomes. Amyloid fibrils trigger various signaling pathways that initiate cellular, metabolic, structural, and functional changes in the heart and other organs. Imaging modalities have advanced to enable detection of amyloid deposits in involved organs and to assess organ dysfunction, disease stage, prognosis, and treatment response. The Amyloidosis Forum hosted a hybrid meeting to focus on the use of imaging endpoints in clinical trials for systemic immunoglobulin light chain amyloidosis and transthyretin amyloidosis. Stakeholders from academia and industry, together with representatives from multiple regulatory agencies reviewed the use of imaging biomarkers with a focus on cardiac amyloidosis, described applications and limitations of imaging in clinical trials, and discussed qualification of imaging as a surrogate clinical outcome. Survey results provided important patient perspectives. This review summarizes the proceedings of the Amyloidosis Forum.</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 5","pages":"Pages 602-617"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donghee Han MD , Evangelos Tzolos MD , Rebekah Park MS , Heidi Gransar MS , Mark Hyun CMNT , John D. Friedman MD , Sean W. Hayes MD , Louise E.J. Thomson MBChB , Alan C. Kwan MD , Matthew Budoff MD , Prediman K. Shah MD , Jacek Kwieciński MD , Sarah Wetzel BS , Chloe Findling BA , Piotr J. Slomka PhD , Damini Dey PhD , Balaji K. Tamarappoo MD, PhD , Daniel S. Berman MD
{"title":"Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography","authors":"Donghee Han MD , Evangelos Tzolos MD , Rebekah Park MS , Heidi Gransar MS , Mark Hyun CMNT , John D. Friedman MD , Sean W. Hayes MD , Louise E.J. Thomson MBChB , Alan C. Kwan MD , Matthew Budoff MD , Prediman K. Shah MD , Jacek Kwieciński MD , Sarah Wetzel BS , Chloe Findling BA , Piotr J. Slomka PhD , Damini Dey PhD , Balaji K. Tamarappoo MD, PhD , Daniel S. Berman MD","doi":"10.1016/j.jcmg.2025.01.005","DOIUrl":"10.1016/j.jcmg.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>The effects of evolocumab on the underlying coronary disease activity by positron emission tomography (PET) and coronary tree plaque composition by coronary computed tomography angiography (CTA) have not been described.</div></div><div><h3>Objectives</h3><div>This prospective imaging study aimed to evaluate changes in coronary plaque composition on coronary CTA and coronary microcalcification, a marker of plaque activity, on <sup>18</sup>F-sodium fluoride (NaF) positron emission tomography (PET) after evolocumab treatment.</div></div><div><h3>Methods</h3><div>This single-arm, prospective, open-label study enrolled patients with baseline extensive noncalcified plaque volume by coronary CTA (>440 µL overall coronary artery or >250 µL in any single plaque). All participants underwent baseline and 18-month follow-up coronary CTA and <sup>18</sup>F-NaF PET. Disease activity was evaluated with <sup>18</sup>F-NaF PET by maximum target-to-background ratios at the lesion level and by coronary microcalcification activity for the entire coronary tree.</div></div><div><h3>Results</h3><div>A total of 47 patients (age 61.8 ± 10.1 years, 87% male) and 196 lesions were studied. Twenty-three (48.9%) patients were asymptomatic, 16 (34%) presented with chest pain, and 8 (17%) presented with dyspnea. Four (8.5%) patients had a prior coronary artery disease history. At a mean follow-up of 18 months, there was no significant change in total plaque volume (716.2 ± 431.4 µL to 710.8 ± 456.2 µL, difference: 5.4 ± 97.4 µL; <em>P =</em> 0.705). Changes in plaque composition were observed, with a significant reduction in noncalcified plaque (607.3 ± 346.8 µL to 562.1 ± 337.3 µL, difference: 45.2 ± 63.8 µL; <em>P <</em> 0.001) and low-attenuation noncalcified plaque (37.1 ± 28.9 µL to 20.4 ± 15.4 µL, difference: 16.6 ± 23.5 µL; <em>P <</em> 0.001). In contrast, there was an increase in calcified plaque (108.9 ± 133.7 µL to 148.7 ± 175.3 µL, difference: 39.8 ± 56.1 µL; <em>P <</em> 0.001). There was a significant reduction in coronary microcalcification activity (1.35 ± 1.68 to 1.08 ± 1.37; <em>P =</em> 0.004) and lesion target-to-background ratio (1.73 ± 0.85 to 1.62 ± 0.83; <em>P =</em> 0.005).</div></div><div><h3>Conclusions</h3><div>In stable patients with extensive noncalcified plaque volume at baseline, 18 months of evolocumab treatment was associated with a shift toward a lower risk quantitative plaque phenotype and reduction in microcalcification activity. (Effect of Evolocumab on Coronary Atherosclerosis; <span><span>NCT03689946</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 5","pages":"Pages 589-599"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yinyin Chen MD, PhD , Hang Jin MD, PhD , Xingming Guan PhD , Hsin-Jung Yang PhD , Xinheng Zhang MS , Zhenhui Chen PhD , Shing Fai Chan PhD , Dhirendra Singh PhD , Nithya Jambunathan PhD , Khalid Youssef PhD , Keyur P. Vora MD, MS , Gabriel Gruionu PhD , Sanjana K. Dharmakumar , Glen Schmeisser MS , Richard Tang MD , Mengsu Zeng MD , Rohan Dharmakumar PhD
{"title":"Detecting Hemorrhagic Myocardial Infarction With 3.0-T CMR","authors":"Yinyin Chen MD, PhD , Hang Jin MD, PhD , Xingming Guan PhD , Hsin-Jung Yang PhD , Xinheng Zhang MS , Zhenhui Chen PhD , Shing Fai Chan PhD , Dhirendra Singh PhD , Nithya Jambunathan PhD , Khalid Youssef PhD , Keyur P. Vora MD, MS , Gabriel Gruionu PhD , Sanjana K. Dharmakumar , Glen Schmeisser MS , Richard Tang MD , Mengsu Zeng MD , Rohan Dharmakumar PhD","doi":"10.1016/j.jcmg.2024.10.006","DOIUrl":"10.1016/j.jcmg.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Hemorrhagic myocardial infarction (hMI) can rapidly diminish the benefits of reperfusion therapy and direct the heart toward chronic heart failure. T2∗ cardiac magnetic resonance (CMR) is the reference standard for detecting hMI. However, the lack of clarity around the earliest time point for detection, time-dependent changes in hemorrhage volume, and the optimal methods for detection can limit the development of strategies to manage hMI.</div></div><div><h3>Objectives</h3><div>The authors investigated CMR signal characteristics of hMI through time-lapse multiparametric mapping using a clinically relevant animal model and evaluated the translatability in ST-segment elevation MI patients when possible.</div></div><div><h3>Methods</h3><div>Canines (N = 20) underwent 3.0-T CMR at baseline and various time points over the first week of reperfused MI. Time-dependent relationships between T1, T2, and T2∗ mapping of hMI, non-hMI, and remote territories were determined. Reperfused ST-segment elevation MI patients (N = 50) were studied to establish clinically feasibility.</div></div><div><h3>Results</h3><div>Although hMI was evident <1 hour after reperfusion on histopathology, it was not reliably detected with T1, T2, or T2∗ CMR. However, 24 hours to 7 days postreperfusion, hMI was detectable on T2∗ (27.0 ± 2.4 ms [baseline] vs 11.7 ± 2.8 ms [hMI]; <em>P <</em> 0.001), with stable volume and transmurality. In T2 maps, hMI was most visible 5 to 7 days postreperfusion with an area under the curve of 0.98 (sensitivity and specificity ≥0.95) relative to T2∗. However, this was not the case with T1 (sensitivity <0.8, across all time points).</div></div><div><h3>Conclusions</h3><div>HMI cannot be reliably detected with T1, T2, or T2∗ on 3.0-T CMR immediately after reperfusion. However, T2∗ CMR can be used to diagnose hMI between 24 hours and 7 days postreperfusion. T2 maps at 3.0-T are a strong alternative to T2∗ maps for diagnosing hMI, provided CMR is performed 5 to 7 days postreperfusion. However, diagnosing hMI with T1 is significantly more challenging at 3.0-T compared with both T2∗ and T2.</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 4","pages":"Pages 436-447"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lars-Egil R. Hammersboen MD , Marie Stugaard MD, PhD , Alexis Puvrez MD , Camilla K. Larsen MD, PhD , Espen W. Remme MSc, PhD , Erik Kongsgård MD, PhD , Jürgen Duchenne MSc, PhD , Elena Galli MD, PhD , Faraz H. Khan MD , Ole Jakob Sletten MD , Martin Penicka MD, PhD , Erwan Donal MD, PhD , Jens-Uwe Voigt MD, PhD , Otto A. Smiseth MD, PhD , John M. Aalen MD, PhD
{"title":"Mechanism and Impact of Left Atrial Dyssynchrony on Long-Term Clinical Outcome During Cardiac Resynchronization Therapy","authors":"Lars-Egil R. Hammersboen MD , Marie Stugaard MD, PhD , Alexis Puvrez MD , Camilla K. Larsen MD, PhD , Espen W. Remme MSc, PhD , Erik Kongsgård MD, PhD , Jürgen Duchenne MSc, PhD , Elena Galli MD, PhD , Faraz H. Khan MD , Ole Jakob Sletten MD , Martin Penicka MD, PhD , Erwan Donal MD, PhD , Jens-Uwe Voigt MD, PhD , Otto A. Smiseth MD, PhD , John M. Aalen MD, PhD","doi":"10.1016/j.jcmg.2024.09.008","DOIUrl":"10.1016/j.jcmg.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Left bundle branch block (LBBB) causes left atrial (LA) dyssynchrony. It is unknown if LA dyssynchrony impacts long-term prognosis.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to determine mechanisms of LA dyssynchrony in LBBB and if LA dyssynchrony impacts long-term prognosis.</div></div><div><h3>Methods</h3><div>In a prospective multicenter study of 168 heart failure patients with LBBB, echocardiographic strain imaging was done before and after 6 months with cardiac resynchronization therapy (CRT). Outcome was assessed after 6 years. Dyssynchrony was measured relative to septum as delay in left ventricular (LV) lateral wall shortening and LA lateral wall stretch. Response to CRT was defined as at least 15% reduction in LV end-systolic volume.</div></div><div><h3>Results</h3><div>Before CRT, there was marked LA dyssynchrony of 105 ± 76 ms, which decreased to 37 ± 68 ms in CRT-responders (<em>P</em> < 0.001), whereas nonresponders showed only a modest reduction in LA dyssynchrony (<em>P</em> < 0.05). There was strong association between LA and LV dyssynchrony (<em>r</em> = 0.70), consistent with direct LV-LA mechanical interaction. CRT caused modest increase in LA reservoir strain (<em>P</em> < 0.01) and marked increase of LV filling time (<em>P</em> < 0.001) in responders. Mortality after 6 years was 21% (35 deaths). LA dyssynchrony did not independently predict mortality. However, the combination of preserved LA reservoir strain (≥18%) and resolved LA dyssynchrony (≤53 ms) after 6 months with CRT was associated with excellent long term-prognosis: HR: 0.11 (95% CI: 0.03-0.42) vs preserved reservoir strain and persistent LA dyssynchrony.</div></div><div><h3>Conclusions</h3><div>LA dyssynchrony in LBBB was attributed to direct LV-LA mechanical interactions. CRT improved diastolic function by increasing LV filling time. Patients with preserved LA reservoir strain and resolution of LA dyssynchrony by CRT had excellent long-term prognosis. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; <span><span>NCT02525185</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 4","pages":"Pages 421-432"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marianna Fontana MD, PhD , Adam Ioannou MBBS, BSc, PhD , Sarah Cuddy MBBCH, BAO , Sharmila Dorbala MD, MPH , Ahmad Masri MD , James C. Moon MD , Vasvi Singh MD , Olivier Clerc MD , Mazen Hanna MD , Fredrick Ruberg MD , Martha Grogan MD , Michele Emdin MD, PhD , Julian Gillmore MD, PhD
{"title":"The Last Decade in Cardiac Amyloidosis","authors":"Marianna Fontana MD, PhD , Adam Ioannou MBBS, BSc, PhD , Sarah Cuddy MBBCH, BAO , Sharmila Dorbala MD, MPH , Ahmad Masri MD , James C. Moon MD , Vasvi Singh MD , Olivier Clerc MD , Mazen Hanna MD , Fredrick Ruberg MD , Martha Grogan MD , Michele Emdin MD, PhD , Julian Gillmore MD, PhD","doi":"10.1016/j.jcmg.2024.10.011","DOIUrl":"10.1016/j.jcmg.2024.10.011","url":null,"abstract":"<div><div>Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment. Whereas conventional therapies have focused on reducing amyloid formation and subsequent stabilization of the cardiac disease process, novel agents are being developed to accelerate the immune-mediated removal of amyloid fibrils from the heart. In this context, the ability to track changes in the amyloid burden over time is of paramount importance. Although advanced imaging techniques have shown efficacy in tracking the treatment response, future research focused on improved precision through use of artificial intelligence may augment the detection of changes earlier in the course of treatment.</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 4","pages":"Pages 478-499"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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