Cardiovascular Magnetic Resonance Identifies High-Risk Systemic Sclerosis Patients with Normal Echocardiograms and Provides Incremental Prognostic Value
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
- Recent-onset supraventricular arrhythmia;
- Recent-onset angina pectoris (AP);
- Sustained or non-sustained ventricular tachycardia (sVT/nsVT);
- Other ventricular rhythm disturbances (VRDs) or;
- Recent onset shortness of breath (SOB).
2.2. Follow-Up, Adverse Outcomes and Clinical Endpoints
2.3. Exclusion Criteria and Ethical Considerations
2.4. Methods
2.5. CMR Data Analysis
2.6. Validation of T1 and T2 Measurements
2.7. Statistical Analysis
3. Results
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Dumoitier, N.; Lofek, S.; Mouthon, L. Pathophysiology of systemic sclerosis: State of the art in 2014. Presse Med. 2014, 43, e267–e278. [Google Scholar] [CrossRef] [PubMed]
- Papagoras, C.; Achenbach, K.; Tsifetaki, N.; Tsiouris, S.; Fotopoulos, A.; Drosos, A.A. Heart involvement in systemic sclerosis: A combined echocardiographic and scintigraphic study. Clin. Rheumatol. 2014, 33, 1105–1111. [Google Scholar] [CrossRef] [PubMed]
- Barnes, J.; Mayes, M.D. Epidemiology of systemic sclerosis: Incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr. Opin. Rheumatol. 2012, 24, 165–170. [Google Scholar] [CrossRef] [PubMed]
- Steen, V.D.; Medsger, T.A. Changes in causes of death in systemic sclerosis, 1972-2002. Ann. Rheum. Dis. 2007, 66, 940–944. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Al-Dhaher, F.F.; Pope, J.E.; Ouimet, J.M. Determinants of Morbidity and Mortality of Systemic Sclerosis in Canada. Semin. Arthritis Rheum. 2010, 39, 269–277. [Google Scholar] [CrossRef] [PubMed]
- Elhai, M.; Meune, C.; Avouac, J.; Kahan, A.; Allanore, Y. Trends in mortality in patients with systemic sclerosis over 40 years: A systematic review and meta-analysis of cohort studies. Rheumatology 2012, 51, 1017–1026. [Google Scholar] [CrossRef] [Green Version]
- Arias-Nuñez, M.C.; Llorca, J.; Vazquez-Rodriguez, T.R.; Gomez-Acebo, I.; Miranda-Filloy, J.A.; Martin, J.; Gonzalez-Juanatey, C.; Gonzalez-Gay, M.A. Systemic Sclerosis in Northwestern Spain. Medicine 2008, 87, 272–280. [Google Scholar] [CrossRef]
- Mok, M.Y.; Lau, C.S. The burden and measurement of cardiovascular disease in SSc. Nat. Rev. Rheumatol. 2010, 6, 430–434. [Google Scholar] [CrossRef]
- Allanore, Y.; Meune, C. Primary myocardial involvement in systemic sclerosis: Evidence for a microvascular origin. Clin. Exp. Rheumatol. 2010, 28, S48–S53. [Google Scholar]
- Ramalho, A.R.; Costa, S.; Silva, F.; Donato, P.; Franco, F.; Pêgo, G.M. Autoimmune myocarditis in systemic sclerosis: An unusual form of scleroderma heart disease presentation. ESC Hear. Fail. 2017, 4, 365–370. [Google Scholar] [CrossRef] [Green Version]
- Mavrogeni, S.; Markousis-Mavrogenis, G. Diffuse, Subendocardial Vasculitis Identified by Cardiovascular Magnetic Resonance. Use of Images to Learn Pathophysiology. J. Vasc. 2016, 2, 1–3. [Google Scholar] [CrossRef]
- Bissell, L.A.; Anderson, M.; Burgess, M.; Chakravarty, K.; Coghlan, G.; Dumitru, R.B.; Graham, L.; Ong, V.; Pauling, J.D.; Plein, S.; et al. Consensus best practice pathway of the UK Systemic Sclerosis Study group: Management of cardiac disease in systemic sclerosis. Rheumatology 2017, 56, 912–921. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mavrogeni, S.; Sfikakis, P.P.; Gialafos, E.; Bratis, K.; Karabela, G.; Stavropoulos, E.; Spiliotis, G.; Sfendouraki, E.; Panopoulos, S.; Bournia, V.; et al. Cardiac tissue characterization and the diagnostic value of cardiovascular magnetic resonance in systemic connective tissue diseases. Arthritis Care Res. 2014, 66, 104–112. [Google Scholar] [CrossRef] [PubMed]
- Mavrogeni, S.I.; Sfikakis, P.P.; Dimitroulas, T.; Koutsogeorgopoulou, L.; Katsifis, G.; Markousis-Mavrogenis, G.; Kolovou, G.; Kitas, G.D. Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives. Rheumatol. Int. 2018, 38, 949–958. [Google Scholar] [CrossRef] [PubMed]
- Mavrogeni, S.; Markousis-Mavrogenis, G.; Koutsogeorgopoulou, L.; Dimitroulas, T.; Bratis, K.; Kitas, G.D.; Sfikakis, P.; Tektonidou, M.; Karabela, G.; Stavropoulos, E.; et al. Cardiovascular magnetic resonance imaging pattern at the time of diagnosis of treatment naïve patients with connective tissue diseases. Int. J. Cardiol. 2017, 236, 151–156. [Google Scholar] [CrossRef] [PubMed]
- Van Den Hoogen, F.; Khanna, D.; Fransen, J.; Johnson, S.R.; Baron, M.; Tyndall, A.; Matucci-Cerinic, M.; Naden, R.P.; Medsger, T.A.; Carreira, P.E.; et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Ann. Rheum. Dis. 2013, 72, 1747–1755. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Friedrich, M.G.; Sechtem, U.; Schulz-Menger, J.; Holmvang, G.; Alakija, P.; Cooper, L.T.; White, J.A.; Abdel-Aty, H.; Gutberlet, M.; Prasad, S.; et al. Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper. J. Am. Coll. Cardiol. 2009, 53, 1475–1487. [Google Scholar] [CrossRef] [Green Version]
- Mavrogeni, S.I.; Sfikakis, P.P.; Markousis-Mavrogenis, G.; Bournia, V.K.; Poulos, G.; Koutsogeorgopoulou, L.; Karabela, G.; Stavropoulos, E.; Katsifis, G.; Boki, K.; et al. Cardiovascular magnetic resonance imaging pattern in patients with autoimmune rheumatic diseases and ventricular tachycardia with preserved ejection fraction. Int. J. Cardiol. 2019, 284, 105–109. [Google Scholar] [CrossRef]
- Rodríguez-Reyna, T.S.; Rosales-Uvera, S.G.; Kimura-Hayama, E.; Hernández-Reyes, P.; Mercado-Velázquez, P.; Benavides-Suárez, S.A.; Esquinca-González, A.; Núñez-Álvarez, C.A. Myocardial fibrosis detected by magnetic resonance imaging, elevated U-CRP and higher mRSS are predictors of cardiovascular complications in systemic sclerosis (SSc) patients. Semin. Arthritis Rheum. 2019. [Google Scholar] [CrossRef]
- Meduri, A.; Di Molfetta, D.V.; Natale, L.; Manfredi, R. Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 4797–4803. [Google Scholar]
- Bosello, S.L.; De Luca, G.; Laria, A.; Berardi, G.; Ferraccioli, G. Poor Outcome in Patients with Systemic Sclerosis and Myocardial Involvement: A Combined Approach Based On Clinical and Laboratory Findings, EKG-Holter and Cardiac Magnetic Resonance. In Proceedings of the 2012 ACR/ARHP Annual Meeting, Washington, DC, USA, 9–14 November 2012; Volume 64. [Google Scholar]
- Pieroni, M.; De Santis, M.; Zizzo, G.; Bosello, S.; Smaldone, C.; Campioni, M.; De Luca, G.; Laria, A.; Meduri, A.; Bellocci, F.; et al. Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: Potential utility of immunosuppressive therapy in cardiac damage progression. Semin. Arthritis Rheum. 2014, 43, 526–535. [Google Scholar] [CrossRef] [PubMed]
- Mavrogeni, S.; Koutsogeorgopoulou, L.; Karabela, G.; Stavropoulos, E.; Katsifis, G.; Raftakis, J.; Plastiras, S.; Noutsias, M.; Markousis-Mavrogenis, G.; Kolovou, G. Silent myocarditis in systemic sclerosis detected by cardiovascular magnetic resonance using Lake Louise criteria. BMC Cardiovasc. Disord. 2017, 17, 187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wells, S.M.; Sleeper, M. Cardiac troponins. J. Vet. Emerg. Crit. Care 2008, 18, 235–245. [Google Scholar] [CrossRef]
- Ferreira, V.M.; Schulz-Menger, J.; Holmvang, G.; Kramer, C.M.; Carbone, I.; Sechtem, U.; Kindermann, I.; Gutberlet, M.; Cooper, L.T.; Liu, P.; et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J. Am. Coll. Cardiol. 2018, 72, 3158–3176. [Google Scholar] [CrossRef]
- Pepe, A.; Meloni, A.; Bruni, C.; De Marchi, D.; Todiere, G.; Fulgenzi, F.; Ghebru, Y.; Guiducci, S.; De Caterina, R.; Matucci Cerinic, M.; et al. P137Prognostic value of cardiac magnetic resonance in systemic sclerosis. Eur. Heart J. Cardiovasc. Imaging 2019, 20. [Google Scholar] [CrossRef] [Green Version]
Variables | No-Event Group | Event Group | p-Value |
---|---|---|---|
Number of Patients | 19 | 31 | N/A |
Demographics: | |||
Sex (female) | 19 (100%) | 27 (87%) | 0.1 |
Age (years) | 56.0 (47.0, 64.0) | 55.0 (40.0, 61.0) | 0.51 |
Years since diagnosis | 3.0 (1.0, 5.0) | 4.0 (2.0, 8.0) | 0.44 |
LV and RV Function: | |||
LVEDV (mL) | 124.0 (93.0, 135.0) | 129.0 (112.0, 152.0) | 0.16 |
LVESV (mL) | 44.0 (30.0, 51.0) | 47.0 (35.0, 76.0) | 0.2 |
LVEF (%) | 65.0 (60.0, 71.0) | 63.0 (51.0, 66.0) | 0.075 |
LV Mass (g) | 61.0 (46.0, 76.0) | 69.0 (58.0, 84.0) | 0.13 |
RVEDV (mL) | 110.0 (94.0, 136.0) | 133.0 (100.0, 156.0) | 0.16 |
RVESV (mL) | 38.0 (31.0, 51.0) | 51.0 (34.0, 69.0) | 0.077 |
RVEF (%) | 65.0 (59.0, 68.0) | 60.0 (50.0, 65.0) | 0.065 |
Elevated high-sensitivity cTnT | 0 (0%) | 9 (29%) | 0.009 * |
Tissue Characterization Indices: | |||
T2 Signal Ratio | 2.2 (1.8, 2.3) | 2.4 (2.0, 2.7) | 0.016 * |
EGE (%) | 1.9 (1.4, 3.4) | 3.8 (2.0, 6.0) | 0.010 * |
LGE (%) | 3.0 (0.0, 5.0) | 6.0 (5.0, 12.0) | <0.001 * |
T2-Mapping (ms) | 55.0 (49.0, 58.0) | 63.0 (55.0, 65.0) | <0.001 * |
Native T1-Mapping (ms) | 1065.0 (1018.0, 1126.0) | 1135.0 (1117.0, 1202.0) | <0.001 * |
Post-contrast T1-Mapping (ms) | 392.5 (360.0, 436.0) | 340.0 (320.0, 391.0) | 0.019 * |
ECV (%) | 30.5 (28.0, 32.0) | 32.0 (31.0, 34.0) | 0.009 * |
Variables | Univariable | Multivariable | ||
---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
T2 Signal Ratio (per 0.2-unit change) | 1.41 (1.06–1.89) | 0.020 * | 1.35 (0.99–1.83) | 0.053 |
EGE (%) | 1.51 (1.07–2.15) | 0.020 * | 1.55 (1.06–2.26) | 0.024 * |
LGE (%) | 1.73 (1.20–2.48) | 0.003 * | 1.81 (1.23–2.67) | 0.003 * |
T2-Mapping (ms) | 1.21 (1.07–1.37) | 0.002 * | 1.20 (1.06–1.36) | 0.004 * |
Native T1-Mapping (per 10 ms change) | 1.19 (1.07–1.33) | 0.002 * | 1.17 (1.04–1.32) | 0.007 * |
Post-contrast T1-Mapping (per 10 ms change) | 0.88 (0.79–0.98) | 0.024 * | 0.86 (0.75–0.98) | 0.025 * |
ECV (%) | 1.25 (0.99–1.64) | 0.051 | 1.22 (0.98–1.52) | 0.066 |
Variables | Univariable | Multivariable | ||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
LVEDV (per 5 mL change) | 1.05 (0.95–1.16) | 0.365 | 1.05 (0.95–1.17) | 0.322 |
LVESV (per 5 mL change) | 1.24 (1.08–1.42) | 0.002 * | 1.25 (1.08–1.45) | 0.003 * |
LVEF (per 5% change) | 0.62 (0.49–0.79) | <0.001 * | 0.63 (0.49–0.81) | <0.001 * |
LV Mass (per 5 g change) | 1.11 (1.01–1.24) | 0.039 * | 1.11 (1.01–1.23) | 0.036 * |
RVEDV (per 5 mL change) | 1.05 (1.01–1.09) | 0.037 * | 1.05 (1.01–1.09) | 0.029 * |
RVESV (per 5 mL change) | 1.08 (1.02–1.14) | 0.005 * | 1.09 (1.03–1.15) | 0.003 * |
RVEF (per 5% change) | 0.70 (0.55–0.90) | 0.006 * | 0.68 (0.53–0.88) | 0.003 * |
T2 Signal Ratio (per 0.2-unit change) | 1.05 (0.85–1.30) | 0.651 | 1.12 (0.89–1.42) | 0.341 |
EGE (%) | 1.09 (0.95–1.24) | 0.226 | 1.11 (0.97–1.27) | 0.140 |
LGE (%) | 1.16 (1.09–1.24) | <0.001 * | 1.20 (1.11–1.30) | <0.001 * |
T2-Mapping (ms) | 1.05 (0.99–1.11) | 0.071 | 1.07 (1.01–1.14) | 0.025 * |
Native T1-Mapping (per 10 ms change) | 1.06 (0.99–1.12) | 0.082 | 1.08 (1.01–1.15) | 0.017 * |
Post-contrast T1-Mapping (per 10 ms change) | 0.96 (0.89–1.04) | 0.366 | 0.93 (0.84–1.03) | 0.182 |
ECV (%) | 1.19 (1.05–1.35) | 0.006 * | 1.18 (1.04–1.34) | 0.011 * |
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Markousis-Mavrogenis, G.; Bournia, V.-K.; Panopoulos, S.; Koutsogeorgopoulou, L.; Kanoupakis, G.; Apostolou, D.; Katsifis, G.; Polychroniadis, M.; Dimitroulas, T.; Kolovou, G.; et al. Cardiovascular Magnetic Resonance Identifies High-Risk Systemic Sclerosis Patients with Normal Echocardiograms and Provides Incremental Prognostic Value. Diagnostics 2019, 9, 220. https://doi.org/10.3390/diagnostics9040220
Markousis-Mavrogenis G, Bournia V-K, Panopoulos S, Koutsogeorgopoulou L, Kanoupakis G, Apostolou D, Katsifis G, Polychroniadis M, Dimitroulas T, Kolovou G, et al. Cardiovascular Magnetic Resonance Identifies High-Risk Systemic Sclerosis Patients with Normal Echocardiograms and Provides Incremental Prognostic Value. Diagnostics. 2019; 9(4):220. https://doi.org/10.3390/diagnostics9040220
Chicago/Turabian StyleMarkousis-Mavrogenis, George, Vasiliki-Kalliopi Bournia, Stylianos Panopoulos, Loukia Koutsogeorgopoulou, George Kanoupakis, Dimitrios Apostolou, Gikas Katsifis, Michail Polychroniadis, Theodoros Dimitroulas, Genovefa Kolovou, and et al. 2019. "Cardiovascular Magnetic Resonance Identifies High-Risk Systemic Sclerosis Patients with Normal Echocardiograms and Provides Incremental Prognostic Value" Diagnostics 9, no. 4: 220. https://doi.org/10.3390/diagnostics9040220