Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis

Kwak, Seo‐Young; Everett, Russell J.; Treibel, Thomas A.; Yang, Seokhun; Hwang, Doyeon; Ko, Taehoon; Williams, Michelle; Bing, Rong; Singh, Trisha; Joshi, Shruti; Lee, Heesun; Lee, Whal; Chin, Calvin Woon-Loong; Fukui, Miho; Musa, Tarique A; Rigolli, Marzia; Singh, Anvesha; Tastet, Lionel; Dobson, Laura E; Wiesemann, Stephanie; Ferreira, Vanessa M.; Captur, Gabriella; Lee, Sahmin; Schulz‐Menger, Jeanette; Schelbert, Erik B.; Clavel, Marie‐Annick; Park, Sung‐Ji; Rheude, Tobias; Hadamitzky, Martin; Gerber, Bernhard; Newby, David E.; Myerson, Saul G.; Cavalcante, João L.; McCann, Gerry P; Greenwood, John P; Moon, James; Dweck, Marc R; Lee, Seung–Pyo

doi:10.1016/j.jacc.2021.05.047

Cited by 45 publications

(19 citation statements)

References 28 publications

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“…Seventy-four percent of our patients had areas of focal fibrosis, 98% of which were the non-infarct type and which were independent of the presence of nonobstructive CAD. Although only 1 or 2 segments were affected by LGE in most patients, data from a recent large multicentre study show that > 2% of LGE in patients with severe AS who undergo AVR is associated with worse postoperative survival [32]. We found, that the myocardium of patients who have progressed to more advanced myocardial injury and have developed areas of irreversible replacement fibrosis on CMR also contains higher degree of diffuse fibrosis measured histologically.…”

Section: Discussionmentioning

confidence: 45%

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study

Balčiūnaitė

Besusparis

Palionis

et al. 2022

Int J Cardiovasc Imaging

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Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=−0.303, p=0.013) and non-invasively (native T1; r=−0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

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Section: Discussionmentioning

confidence: 45%

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study

Balčiūnaitė

Besusparis

Palionis

et al. 2022

Int J Cardiovasc Imaging

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“…Such parameters could include the presence of mid-wall late gadolinium enhancement of cardiovascular magnetic resonance, utilisation of left ventricular stroke volume in preference to LVEF or various biomarkers (eg, N-terminal pro b-type natriuretic peptide/BNP, high-sensitivity troponin), which are associated with a worse outcome 32–35. These clues could help refine the optimal timing of intervention for each patient 35–37. The results of currently ongoing randomised trials investigating these parameters are greatly anticipated to help clarify the role of these parameters in the risk assessment of patients with severe aortic stenosis and the impact of early intervention on the outcome and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

et al. 2022

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ObjectivesThe management of severe aortic stenosis mandates consideration of aortic valve intervention for symptomatic patients. However, for asymptomatic patients with severe aortic stenosis, recent randomised trials supported earlier intervention. We conducted a systematic review and meta-analysis to evaluate all the available data comparing the two management strategies.MethodsPubMed, Cochrane and Web of Science databases were systematically searched from inception until 10 January 2022. The search key terms were ‘asymptomatic’, ‘severe aortic stenosis’ and ‘intervention’.ResultsMeta-analysis of two published randomised trials, AVATAR and RECOVERY, included 302 patients and showed that early intervention resulted in 55% reduction in all-cause mortality (HR=0.45, 95% CI 0.24 to 0.86; I2 0%) and 79% reduction in risk of hospitalisation for heart failure (HR=0.21, 95% CI 0.05 to 0.96; I2 15%). There was no difference in risk of cardiovascular death between the two groups (HR=0.36, 95% CI 0.03 to 3.78; I2 78%). Additionally, meta-analysis of eight observational studies showed improved mortality in patients treated with early intervention (HR=0.38, 95% CI 0.26 to 0.56; I2 77%).ConclusionThis meta-analysis provides evidence that, in patients with severe asymptomatic aortic stenosis, early intervention reduces all-cause mortality and improves outcomes compared with conservative management. While this is very encouraging, further randomised controlled studies are needed to draw firm conclusions and identify the optimal timing of intervention.PROSPERO registration numberCRD42022301037.

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“…Thus, it is tempting to speculate that the uncommon simultaneous drop of cardiac T1 and T2 might be useful as a premature in vivo readout for mitochondrial disorders in the heart, which could be even more sensitive than conventional parameters of myocardial damage, such as ECV, LGE, etc. [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis

et al. 2022

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Aortic valve stenosis (AS) is the most frequent valve disease with relevant prognostic impact. Experimental model systems for AS are scarce and comprehensive imaging techniques to simultaneously quantify function and morphology in disease progression are lacking. Therefore, we refined an acute murine AS model to closely mimic human disease characteristics and developed a high-resolution magnetic resonance imaging (MRI) approach for simultaneous in-depth analysis of valvular, myocardial as well as aortic morphology/pathophysiology to identify early changes in tissue texture and critical transition points in the adaptive process to AS. AS was induced by wire injury of the aortic valve. Four weeks after surgery, cine loops, velocity, and relaxometry maps were acquired at 9.4 T to monitor structural/functional alterations in valve, aorta, and left ventricle (LV). In vivo MRI data were subsequently validated by histology and compared to echocardiography. AS mice exhibited impaired valve opening accompanied by significant valve thickening due to fibrotic remodelling. While control mice showed bell-shaped flow profiles, AS resulted not only in higher peak flow velocities, but also in fragmented turbulent flow patterns associated with enhanced circumferential strain and an increase in wall thickness of the aortic root. AS mice presented with a mild hypertrophy but unaffected global LV function. Cardiac MR relaxometry revealed reduced values for both T1 and T2 in AS reflecting subtle myocardial tissue remodelling with early alterations in mitochondrial function in response to the enhanced afterload. Concomitantly, incipient impairments of coronary flow reserve and myocardial tissue integrity get apparent accompanied by early troponin release. With this, we identified a premature transition point with still compensated cardiac function but beginning textural changes. This will allow interventional studies to explore early disease pathophysiology and novel therapeutic targets.

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Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis

Cited by 45 publications

References 28 publications

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis

Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis

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