Clinical Role of CA125 in Worsening Heart Failure A BIOSTAT-CHF Study Subanalysis

OBJECTIVES The aim of this study was to evaluate the association between antigen carbohydrate 125 (CA125) and the risk of 1-year clinical outcomes in patients with worsening heart failure (HF).BACKGROUND CA125 is a widely available biomarker that is up-regulated in patients with acute HF and has been postulated as a useful marker of congestion and risk stratification.METHODS hi a large multicenter cohort of patients with worsening HF, either in-hospital or in the outpatient setting, the independent associations between CA125 and 1-year death and the composite of death/HF readmission (adjusted for outcome-specific prognostic risk score [BIOSTAT risk score]) were determined by using the Royston-Parmar method (N = 2356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a composite congestion score (CCS). Data were validated in the B1OSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure validation) cohort (N = 1,630).RESULTS Surrogates of congestion, such as N-terminal pro-B-type natriuretic peptide and CCS, emerged as independent predictors of CA125. In muttivariabte survival analyses, higher CA125 was associated with an increased risk of mortality and the composite of death/HF readmission (p &lt;0.001 for both comparisons), even after adjustment for the CCS (p &lt;0.010 for both comparisons). The addition of CA125 to the B1OSTAT score led to a significant risk reclassification for both outcomes (category-free net reclassification improvement 0.137 [p &lt;0.001] and 0.104 [p 0.003] respectively). AR outcomes were confirmed in an independent validation cohort.CONCLUSIONS In patients with worsening HF, higher levels of CA125 were positively associated with parameters of congestion. Furthermore, CA125 remained independently associated with a higher risk of clinical outcomes, even beyond a predefined risk model and clinical surrogates of congestion. (C) 2020 by the American College of Cardiology Foundation.</p

Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients

[EN] Background older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce. Methods the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI). Results during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02-1.04], P 155, LVEF = 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P < 0.001). Conclusions CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI-CMR score should be externally validated.This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI20/00637, PI15/00531, and CIBERCV16/11/00486,CIBERCV16/11/00420, CIBERCV16/11/00479), apostgraduate contract FI18/00320 to C.R.-N., CM21/00175 to V.M.-G. and JR21/00041 to C.B., Fundacio La MaratoTV3 (grant 20153030-31-32), La Caixa Banking Foundation (HR17-00527), by Conselleria de Educacion-Generalitat Valenciana (PROMETEO/2021/008) and by Sociedad Espanola de Cardiologia (grant SEC/FEC-INV-CLI 21/024). J.G. acknowledges financial support from the Agencia Estatal de Investigacion (grant FJC2020-043981-I/AEI/10.13039/501100011033). D.M. acknowledges financial support from the Conselleria d'Educacio,Investigacio, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037, AEST/2020/029).Gabaldón-Pérez A; Marcos-Garcés, V.; Gavara-Doñate, J.; López-Lereu, MP.; Monmeneu, JV.; Pérez, N.; Ríos-Navarro, C.... (2022). Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients. Age and Ageing. 51(11):1-11. https://doi.org/10.1093/ageing/afac248111511

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

Background: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. Methods: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. Results: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). Conclusion: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction

Clinical Predictors and Prognosis of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) without ST-Segment Elevation in Older Adults

A non-neglectable percentage of patients with non-ST elevation myocardial infarction (NSTEMI) show non-obstructive coronary arteries (MINOCA). Specific data in older patients are scarce. We aimed to identify the clinical predictors of MINOCA in older patients admitted for NSTEMI and to explore the long-term prognosis of MINOCA. This was a single-center, observational, consecutive cohort study of older (&ge;70 years) patients admitted for NSTEMI between 2010 and 2014 who underwent coronary angiography. Univariate and multivariate Cox regression were performed to analyze the association of variables with MINOCA and all-cause mortality and with major adverse cardiac events (MACE), defined as a combined endpoint of all-cause mortality and nonfatal myocardial infarction and a combined endpoint of cardiovascular mortality, nonfatal myocardial infarction, and unplanned revascularization. The registry included 324 patients (mean age 78.8 &plusmn; 5.4 years), of which 71 (21.9%) were diagnosed with MINOCA. Predictors of MINOCA were female sex, left bundle branch block, pacemaker rhythm, chest pain at rest, peak troponin level, previous MI, Killip &ge;2, and ST segment depression. Regarding prognosis, patients with obstructive coronary arteries (stenosis &ge;50%) and the subgroup of MINOCA patients with plaques &lt;50% had a similar prognosis; while MINOCA patients with angiographically smooth coronary arteries had a reduced risk of MACE. We conclude that the following: (1) in elderly patients admitted for NSTEMI, certain universally available clinical, electrocardiographic, and analytical variables are associated with the diagnosis of MINOCA; (2) elderly patients with MINOCA have a better prognosis than those with obstructive coronary arteries; however, only those with angiographically smooth coronary arteries have a reduced risk of all-cause mortality and MACE

Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size in Post-PCI Patients

ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI). In the animal model, a sharp drop in circulating T lymphocytes occurred within the first hours after reperfusion. Notably, increased apoptosis of circulating lymphocytes and infiltration of proinflammatory Th1 lymphocytes in the heart were observed 48 h after reperfusion. Similarly, in STEMI patients, a sharp drop in circulating T lymphocyte subsets occurred within the first 24 h post-PCI. A cardiac magnetic resonance (CMR) evaluation of these patients revealed an inverse association between 24 h circulating T lymphocyte numbers and infarction size at 1-week and 6-month post-PCI. Our translational approach revealed striking changes in the circulating and tissue-infiltrating T lymphocyte repertoire in response to ischemia-reperfusion. These findings may help in developing new diagnostic and therapeutic approaches for coronary diseases

Ejection Fraction by Echocardiography for a Selective Use of Magnetic Resonance After Infarction

[EN] Background Cardiac magnetic resonance (CMR) permits robust risk stratification of discharged ST-segment-elevation myocardial infarction patients, but its indiscriminate use in all cases is not feasible. We evaluated the utility of left ventricular ejection fraction (LVEF) by echocardiography for a selective use of CMR after ST-segment-elevation myocardial infarction. Methods Echocardiography and CMR were performed in 1119 patients discharged for ST-segment-elevation myocardial infarction included in a multicenter registry. The prognostic power of CMR beyond echocardiography-LVEF was assessed using adjusted C statistic, net reclassification improvement index, and integrated discrimination improvement index. Results During a 4.8-year median follow-up, 136 (12%) first major adverse cardiac events (MACE) occurred (47 cardiovascular deaths and 89 readmissions for acute heart failure). In the entire group, CMR-LVEF (but not echocardiography-LVEF) independently predicted MACE occurrence. The MACE rate significantly increased only in patients with CMR-LVEF= 50%: 7%, 40%-49%: 9%, = 50% (629, 56%), and they had a low MACE rate (57/629, 9%). In patients with echocardiography-LVEF= 40% (24/278, 9%) but significantly increased in patients with CMR-LVEF= 50% (C statistic 0.66 versus 0.66; net reclassification improvement index, 0.17; integrated discrimination improvement index, 0.01). Conclusions A straightforward strategy based on a selective use of CMR for risk prediction in ST-segment-elevation myocardial infarction patients with echocardiography-LVEF<50% can provide insights into patient care. The cost-effectiveness of this approach, as well as the direct implications in clinical management, should be further explored.This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI15/00531, PI17/01836, PI20/00637 and, CIBERCV16/11/00486), Marato TV3 (grant number 20153030-31-32), a grant from the Catalonian Society of Cardiology 2015, and Generalitat Valenciana (grant number GV/2018/116). The study was partially funded by Siemens Healthcare, which provided financial support to conduct CMR studies in 94 subjects of this series. D.M. acknowledges financial support from the Agencia Valenciana de la Innovacion, Generalitat Valenciana (grant number INNCAD00/19/085), and from the Conselleria d'Educacio, Investigacio, Cultura i Esport, Generalitat Valenciana (grant number AEST/2019/037).Marcos-Garces, V.; Gavara, J.; Lopez-Lereu, MP.; Monmeneu, JV.; Rios-Navarro, C.; De Dios, E.; Pérez, N.... (2020). Ejection Fraction by Echocardiography for a Selective Use of Magnetic Resonance After Infarction. Circulation Cardiovascular Imaging. 13(12):1-11. https://doi.org/10.1161/CIRCIMAGING.120.011491S1111312Nabel, E. G., & Braunwald, E. (2012). A Tale of Coronary Artery Disease and Myocardial Infarction. New England Journal of Medicine, 366(1), 54-63. doi:10.1056/nejmra1112570Pedersen, F., Butrymovich, V., Kelbæk, H., Wachtell, K., Helqvist, S., Kastrup, J., … Jørgensen, E. (2014). Short- and Long-Term Cause of Death in Patients Treated With Primary PCI for STEMI. Journal of the American College of Cardiology, 64(20), 2101-2108. doi:10.1016/j.jacc.2014.08.037Bahit, M. C., Kochar, A., & Granger, C. B. (2018). Post-Myocardial Infarction Heart Failure. JACC: Heart Failure, 6(3), 179-186. doi:10.1016/j.jchf.2017.09.015Gho, J. M. I. H., Postema, P. G., Conijn, M., Bruinsma, N., de Jong, J. S. S. G., Bezzina, C. R., … Asselbergs, F. W. (2017). Heart failure following STEMI: a contemporary cohort study of incidence and prognostic factors. Open Heart, 4(2), e000551. doi:10.1136/openhrt-2016-000551Ibanez, B., James, S., Agewall, S., Antunes, M. J., Bucciarelli-Ducci, C., Bueno, H., … Halvorsen, S. (2017). 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal, 39(2), 119-177. doi:10.1093/eurheartj/ehx393Bulluck, H., Dharmakumar, R., Arai, A. E., Berry, C., & Hausenloy, D. J. (2018). Cardiovascular Magnetic Resonance in Acute ST-Segment–Elevation Myocardial Infarction. Circulation, 137(18), 1949-1964. doi:10.1161/circulationaha.117.030693Gavara, J., Rodriguez-Palomares, J. F., Valente, F., Monmeneu, J. V., Lopez-Lereu, M. P., Bonanad, C., … Bodi, V. (2018). Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction. JACC: Cardiovascular Imaging, 11(10), 1448-1457. doi:10.1016/j.jcmg.2017.09.017Cambronero-Cortinas, E., Bonanad, C., Monmeneu, J. V., Lopez-Lereu, M. P., Gavara, J., de Dios, E., … Bodi, V. (2017). Incidence, Outcomes, and Predictors of Ventricular Thrombus after Reperfused ST-Segment–Elevation Myocardial Infarction by Using Sequential Cardiac MR Imaging. Radiology, 284(2), 372-380. doi:10.1148/radiol.2017161898Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., … van der Meer, P. (2016). 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal, 37(27), 2129-2200. doi:10.1093/eurheartj/ehw128Piepoli, M. F., Hoes, A. W., Agewall, S., Albus, C., Brotons, C., Catapano, A. L., … Verschuren, W. M. M. (2016). 2016 European Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 37(29), 2315-2381. doi:10.1093/eurheartj/ehw106Bodi, V., Sanchis, J., Nunez, J., Mainar, L., Lopez-Lereu, M. P., Monmeneu, J. V., … Llacer, A. (2009). Prognostic Value of a Comprehensive Cardiac Magnetic Resonance Assessment Soon After a First ST-Segment Elevation Myocardial Infarction. JACC: Cardiovascular Imaging, 2(7), 835-842. doi:10.1016/j.jcmg.2009.03.011Bodi, V. (2019). Strain by Feature Tracking. JACC: Cardiovascular Imaging, 12(7), 1199-1201. doi:10.1016/j.jcmg.2018.08.009Mukherjee, J. T., Beshansky, J. R., Ruthazer, R., Alkofide, H., Ray, M., Kent, D., … Selker;, H. P. (2015). In-hospital measurement of left ventricular ejection fraction and one-year outcomes in acute coronary syndromes: results from the IMMEDIATE Trial. Cardiovascular Ultrasound, 14(1). doi:10.1186/s12947-016-0068-1Perelshtein Brezinov, O., Klempfner, R., Zekry, S. B., Goldenberg, I., & Kuperstein, R. (2017). Prognostic value of ejection fraction in patients admitted with acute coronary syndrome. Medicine, 96(9), e6226. doi:10.1097/md.0000000000006226Bodi, V., Monmeneu, J. V., Ortiz-Perez, J. T., Lopez-Lereu, M. P., Bonanad, C., Husser, O., … Chorro, F. J. (2016). Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment–Elevation Myocardial Infarction: Results of a Large Prospective Registry. Radiology, 278(1), 54-63. doi:10.1148/radiol.2015142674Rodriguez-Palomares, J. F., Gavara, J., Ferreira-González, I., Valente, F., Rios, C., Rodríguez-García, J., … García-Dorado, D. (2019). Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI. JACC: Cardiovascular Imaging, 12(12), 2445-2456. doi:10.1016/j.jcmg.2019.02.025Bodí, V., Sanchis, J., López-Lereu, M. P., Losada, A., Núñez, J., Pellicer, M., … Llácer, À. (2005). Usefulness of a Comprehensive Cardiovascular Magnetic Resonance Imaging Assessment for Predicting Recovery of Left Ventricular Wall Motion in the Setting of Myocardial Stunning. Journal of the American College of Cardiology, 46(9), 1747-1752. doi:10.1016/j.jacc.2005.07.039Van Kranenburg, M., Magro, M., Thiele, H., de Waha, S., Eitel, I., Cochet, A., … van Geuns, R.-J. (2014). Prognostic Value of Microvascular Obstruction and Infarct Size, as Measured by CMR in STEMI Patients. JACC: Cardiovascular Imaging, 7(9), 930-939. doi:10.1016/j.jcmg.2014.05.010Grothues, F., Smith, G. C., Moon, J. C. ., Bellenger, N. G., Collins, P., Klein, H. U., & Pennell, D. J. (2002). Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. The American Journal of Cardiology, 90(1), 29-34. doi:10.1016/s0002-9149(02)02381-

Head-to-head comparison of 1 week versus 6 months CMR-derived infarct size for prediction of late events after STEMI

Infarct size (IS) at 1 week after ST-elevation myocardial infarction (MI) diminishes during the first months. The incremental prognostic value of IS regression and of scar size (SS) at 6 months is unknown. We compared cardiovascular magnetic resonance (CMR)-derived IS at 1 week and SS at 6 months after MI for predicting late major adverse cardiac events (MACE). 250 patients underwent CMR at 1 week and 6 months after MI. IS and SS were determined as the extent of transmural late enhancement (in > 50 % of wall thickness, ETLE). During 163 weeks, 23 late MACE (cardiac death, MI or readmission for heart failure after the 6 months CMR) occurred. Patients with MACE had a larger IS at 1 week (6 [4-9] vs. 3 [1-5], p median were higher at 1 week (14 vs. 4 %, p = .007) and in SS > median at 6 months (12 vs. 5 %, p = .053). The C-statistic for predicting late MACE of CMR at 1 week and 6 months was comparable (.720 vs. .746, p = .1). Only ETLE at 1 week (HR 1.31 95 % CI [1.14-1.52], p < .0001, per segment) independently predicted late MACE. CMR-derived SS at 6 months does not offer prognostic value beyond IS at 1 week after MI. The strongest predictor of late MACE is ETLE at 1 week.y This work was supported by the "Instituto de Salud Carlos III" (PI1102323 grant). O. Husser was supported by the "Regensburger Forschungsforderung in der Medizin (ReForM)".Husser, O.; Monmeneu Menadas, JV.; Bonanad, C.; Gomez, C.; Chaustre, F.; Nuñez, J.; López Lereu, MP.... (2013). Head-to-head comparison of 1 week versus 6 months CMR-derived infarct size for prediction of late events after STEMI. International Journal of Cardiovascular Imaging. 29(7):1499-1509. https://doi.org/10.1007/s10554-013-0239-1S14991509297Perazzolo Marra M, Lima JA, Iliceto S (2011) MRI in acute myocardial infarction. Eur Heart J 32:284–293. doi: 10.1093/eurheartj/ehq409Hombach V, Merkle N, Kestler HA, Torzewski J, Kochs M et al (2008) Characterization of patients with acute chest pain using cardiac magnetic resonance imaging. Clin Res Cardiol 97:760–767Kim RJ, Wu E, Rafael A, Chen EL, Parker MA et al (2000) The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 343:1445–1453. doi: 10.1056/NEJM200011163432003Bodí V, Husser O, Sanchis J, Núñez J, López-Lereu MP et al (2010) Contractile reserve and extent of transmural necrosis in the setting of myocardial stunning: comparison at cardiac MR imaging. Radiology 255:755–763. doi: 10.1148/radiol.10091191Bodi V, Sanchis J, Nunez J, Mainar L, Lopez-Lereu MP et al (2009) Prognostic value of a comprehensive cardiac magnetic resonance assessment soon after a first ST-segment elevation myocardial infarction. JACC Cardiovasc Imaging 2:835–842. doi: 10.1016/j.jcmg.2009.03.011Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA et al (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97:765–772Hombach V, Grebe O, Merkle N, Waldenmaier S, Hoher M et al (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26:549–557de Waha S, Desch S, Eitel I, Fuernau G, Lurz P et al (2012) Relationship and prognostic value of microvascular obstruction and infarct size in ST-elevation myocardial infarction as visualized by magnetic resonance imaging. Clin Res Cardiol 101:487–495. doi: 10.1007/s00392-012-0419-3Yan AT, Gibson CM, Larose E, Anavekar NS, Tsang S et al (2006) Characterization of microvascular dysfunction after acute myocardial infarction by cardiovascular magnetic resonance first-pass perfusion and late gadolinium enhancement imaging. J Cardiovasc Magn Reson 8:831–837. doi: 10.1080/10976640600778049Ørn S, Manhenke C, Greve OJ, Larsen AI, Bonarjee VV et al (2009) Microvascular obstruction is a major determinant of infarct healing and subsequent left ventricular remodelling following primary percutaneous coronary intervention. Eur Heart J 30:1978–1985. doi: 10.1093/eurheartj/ehp219Ingkanisorn WP, Rhoads KL, Aletras AH, Kellman P, Arai AE (2004) Gadolinium delayed enhancement cardiovascular magnetic resonance correlates with clinical measures of myocardial infarction. J Am Coll Cardiol 43:2253–2259. doi: 10.1016/j.jacc.2004.02.046Fieno DS, Hillenbrand HB, Rehwald WG, Harris KR, Decker RS et al (2004) Infarct resorption, compensatory hypertrophy, and differing patterns of ventricular remodeling following myocardial infarctions of varying size. J Am Coll Cardiol 43:2124–2131. doi: 10.1016/j.jacc.2004.01.043Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57:891–903. doi: 10.1016/j.jacc.2010.11.013van den Borne SW, Diez J, Blankesteijn WM, Verjans J, Hofstra L, Narula J (2010) Myocardial remodeling after infarction: the role of myofibroblasts. Nat Rev Cardiol 7:30–37. doi: 10.1038/nrcardio.2009.199Henriques JP, Zijlstra F, van‘t Hof AW, de Boer MJ, Dambrink JH et al (2003) Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 107:2115–2119. doi: 10.1161/01.CIR.0000065221.06430.EDBodi V, Sanchis J, Lopez-Lereu MP, Nunez J, Mainar L et al (2009) Prognostic and therapeutic implications of dipyridamole stress cardiovascular magnetic resonance on the basis of the ischaemic cascade. Heart 95:49–55. doi: 10.1136/hrt.2007.139683Stehling MK, Holzknecht NG, Laub G, Böhm D, von Smekal A, Reiser M (1996) Single-shot T1- and T2-weighted magnetic resonance imaging of the heart with black blood: preliminary experience. MAGMA 4:231–240Simonetti OP, Finn JP, White RD, Laub G, Henry DA (1996) “Black blood” T2-weighted inversion-recovery MR imaging of the heart. Radiology 199:49–57Abdel-Aty H, Boyé P, Zagrosek A, Wassmuth R, Kumar A et al (2005) Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol 45:1815–1822. doi: 10.1016/j.jacc.2004.11.069Bodi V, Sanchis J, Lopez-Lereu MP, Nunez J, Mainar L et al (2007) Prognostic value of dipyridamole stress cardiovascular magnetic resonance imaging in patients with known or suspected coronary artery disease. J Am Coll Cardiol 50:1174–1179. doi: 10.1016/j.jacc.2007.06.016Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S et al (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105:539–542Husser O, Bodi V, Sanchis J, Nunez J, Lopez-Lereu MP et al (2011) Predictors of cardiovascular magnetic resonance-derived microvascular obstruction on patient admission in STEMI. Int J Cardiol. doi: 10.1016/j.ijcard.2011.09.083Monmeneu JV, Bodi V, Sanchis J, Lopez-Lereu MP, Mainar L et al (2009) Cardiac magnetic resonance evaluation of edema after ST-elevation acute myocardial infarction. Rev Esp Cardiol 62:858–866Thygesen K, Alpert JS, White HD (2007) Universal definition of myocardial infarction. J Am Coll Cardiol 50:2173–2195Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P et al (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442Saeed M, Lund G, Wendland MF, Bremerich J, Weinmann H, Higgins CB (2001) Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation 103:871–876Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92:139–150Bodi V, Sanchis J, Lopez-Lereu MP, Losada A, Nunez J et al (2005) Usefulness of a comprehensive cardiovascular magnetic resonance imaging assessment for predicting recovery of left ventricular wall motion in the setting of myocardial stunning. J Am Coll Cardiol 46:1747–1752Wu E, Ortiz JT, Tejedor P, Lee DC, Bucciarelli-Ducci C et al (2008) Infarct size by contrast enhanced cardiac magnetic resonance is a stronger predictor of outcomes than left ventricular ejection fraction or end-systolic volume index: prospective cohort study. Heart 94:730–736Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C et al (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33:2569–2619. doi: 10.1093/eurheartj/ehs215Wu KC, Kim RJ, Bluemke DA, Rochitte CE, Zerhouni EA et al (1998) Quantification and time course of microvascular obstruction by contrast-enhanced echocardiography and magnetic resonance imaging following acute myocardial infarction and reperfusion. J Am Coll Cardiol 32:1756–1764Eitel I, Kubusch K, Strohm O, Desch S, Mikami Y et al (2011) Prognostic value and determinants of a hypointense infarct core in T2-weighted cardiac magnetic resonance in acute reperfused ST-elevation-myocardial infarction. Circ Cardiovasc Imaging 4:354–362Ganame J, Messalli G, Dymarkowski S, Rademakers FE, Desmet W et al (2009) Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction. Eur Heart J 30:1440–1449Carlsson M, Ubachs JF, Hedström E, Heiberg E, Jovinge S, Arheden H (2009) Myocardium at risk after acute infarction in humans on cardiac magnetic resonance: quantitative assessment during follow-up and validation with single-photon emission computed tomography. JACC Cardiovasc Imaging 2:569–576. doi: 10.1016/j.jcmg.2008.11.01

Longitudinal strain in remote non-infarcted myocardium by tissue tracking CMR: characterization, dynamics, structural and prognostic implications

[EN] Purpose In ST-segment elevation myocardial infarction (STEMI) patients, longitudinal strain (LS) in remote non-infarcted myocardium (RNM) has not yet been characterized by tissue tracking (TT) cardiovascular magnetic resonance (CMR). In STEMI patients, we aimed to characterize RNM-LS by TT-CMR and to assess both its dynamics and its structural and prognostic implications. Methods We recruited 271 patients with a first STEMI studied with TT-CMR 1 week after infarction. Of these patients, 145 underwent 1-week and 6-month TT-CMR and were used to characterize both the dynamics and the short-term and long-term structural implications of RNM-LS. Based on previously validated data, RNM areas were defined depending on the culprit coronary artery. Results Reduced RNM-LS at 1 week (n = 70, 48%) was associated with larger infarct size and more depressed left ventricular ejection fraction (LVEF) at both the 1-week and 6-month TT-CMR (p value < 0.001). Late normalization of RNM-LS was frequent (28/70, 40%) and independently related to late recovery of LVEF (p value = 0.002). Patients with reduced RNM-LS at 1-week TT-CMR had more major adverse cardiac events (death, heart failure or re-infarction) in both the 271 patients included in the study group (26% vs. 11%, p value = 0.002) and in an external validation cohort made up of 177 STEMI patients (57% vs. 13%, p value < 0.001). Conclusion After STEMI, reduced RNM-LS by TT-CMR is common and is associated with more severe short- and long-term structural damage. There is a beneficial tendency towards recovery of RNM-LS that parallels late recovery of LVEF. More events occur in patients with reduced RNM-LS.This work was supported by the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) [Grant Numbers PI17/01836, PIE15/00013, CIBERCV16/11/00486, CIBERCV16/11/00479 and a postgraduate contract FI18/00320 to C. R.-N.] and by the Generalitat Valenciana [Grant Number GV/2018/116]. JG and DM acknowledge financial support from the Agencia Valenciana de la Innovacio, Generalitat Valenciana (Grant INNCAD00/18/026).Gavara-Doñate, J.; Rodríguez-Palomares, JF.; Rios-Navarro, C.; Valente, F.; Monmeneu, JV.; Lopez-Lereu, MP.; Ferreira-González, I.... (2021). Longitudinal strain in remote non-infarcted myocardium by tissue tracking CMR: characterization, dynamics, structural and prognostic implications. International Journal of Cardiovascular Imaging. 37(1):241-253. https://doi.org/10.1007/s10554-020-01890-wS24125337

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine

Background: Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model. Methods: A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angio-plasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an angioplasty balloon-induced anterior STEMI model, MVO was defined as the % of area at risk without thioflavin-S staining. Results: In patients, PCON (n = 49) in comparison with non-PCON (n = 52) did not significantly reduce MVO (0 [0-1.02]% vs. 0 [0-2.1]% p = 0.2) or IS (18 +/- 13% vs. 21 +/- 14%, p = 0.2). MVO (>1 segment in the 17-segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients, p = 0.3. No significant differences were observed between PCON and non-PCON patients in left ventricular volumes, ejection fraction or the extent of hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%) non-PCON pigs, p = 0.9. The extent of MVO (10 +/- 7% vs. 10 +/- 8%, p = 0.9) and infarct size (23 +/- 14% vs. 24 +/- 10%, p = 0.8) was not reduced in PCON compared with non-PCON pigs. Conclusions: Ischemic postconditioning does not significantly reduce microvascular obstruction in ST-segment elevation myocardial infarction.The present study was supported by the "Instituto de Salud Carlos III" (PI1102323 grant), FEDER, the "Conselleria de Educacio, Cultura i Esport de la Generalitat Valenciana" (PROMETEO/2013/007 grant) and by the Regensburger Forschungsforderung in der Medizin (ReForM).Bodí, V.; Ruiz Nodar, JM.; Feliu, E.; Minana, G.; Nuñez, J.; Husser, O.; Martinez Elvira, J.... (2014). Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine. International Journal of Cardiology. 175(1):138-146. https://doi.org/10.1016/j.ijcard.2014.05.003S138146175

Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum A Translational Study Based on Transient Coronary Occlusion Models

Objectives The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. Background Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. Methods High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). Results Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). Conclusions This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients. (J Am Coll Cardiol 2012;59:1629-41) (c) 2012 by the American College of Cardiology FoundationFrom the *Cardiology Department, Hospital Clinico Universitario-INCLIVA, Universidad de Valencia, Valencia, Spain; dagger Unidad Central de Investigacion en Medicina, Universidad de Valencia, Valencia, Spain; double dagger Centro de Biomateriales e Ingenier a Tisular, Universidad Politecnica de Valencia, Valencia, Spain; Department of Clinical Analyses, Hospital Clinico Universitario-INCLIVA, Valencia, Spain; parallel to Cardiology Department, Hospital Clinic, IDIBAPS, Universidad de Barcelona, Barcelona, Spain; Department of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; and the #Fundacion Investigacion, Hospital Clinico Universitario-INCLIVA, Valencia, Spain. The present study was supported by Instituto de Salud Carlos III (PI 11/02323 and Heracles grants to Dr. Bodi), Fundacion Gent per Gent (to Drs. Bodi and Monleon), the Ministry of Science and Innovation of Spain (grant SAF2008- 00270 to Dr. Monleon), and Generalitat Valenciana (grant GVASAN AP014/2009 to Dr. Monleon and grant PROMETEO2010-075 to Dr. Vina). Dr. Monleon gratefully acknowledges a 2006 Ramon y Cajal contract from the Ministry of Education of Spain. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Bodi, V.; Sanchis, J.; Morales, JM.; Marrachelli, VG.; Nunez, J.; Forteza, MJ.; Chaustre Mendoza, LF.... (2012). Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum A Translational Study Based on Transient Coronary Occlusion Models. Journal of the American College of Cardiology. 59(18):1629-1641. https://doi.org/10.1016/j.jacc.2011.09.083S16291641591