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Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated Cardiomyopathy Results of the IMAC

The IMAC-2 study 1 sought to elucidate the prognosis and natural history of recent onset cardiomyopathy (ROCM) under contemporary heart failure (HF) treatment. 373 ROCM patients (38% females; 21% blacks; mean age: 45±14 years; duration of symptoms: 2.2±1.7 months) were enrolled at 16 centers from May 2002 through December 2008. LVEF was assessed by transthoracic echocardiography at study entry and at 6 months, and patients were followed up for up to 48 months. The primary outcome was change in LVEF from baseline to 6 months. The secondary outcomes included transplant-free and hospitalization-free survival. The majority of the patients received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (91%) and beta-blockers (82%) at study entry, which increased to 92% and 94% at 6 months, respectively. Moreover, 67% of the patients received loop diuretics, and 27% aldosterone receptor antagonists at study entry.

LVEF rose from 0.24±0.08% at entry and 0.40±0.12% at 6 months (mean LVEF increase: 17±13%). At 6 months, 70% of the patients demonstrated an increase of >10 EF units, and 39% demonstrated an increase of > 20 EF units. 40% had an LVEF of 0.45 or more at 6 months, and the LVEF had normalized (> 0.50) in 25% of the patients. Transplant-free survival at 1, 2, and 4 years was 94%, 92%, and 88%, respectively. Furthermore, survival free of heart failure hospitalization was 88%, 82%, and 78%, respectively.

NYHA functional class IV was associated with a significantly higher risk of death/transplantation over 4 years of follow-up. In contrast, female sex was associated with a significantly lower risk of death/transplantation. In analyses adjusted for sex, baseline LVEF, and blood pressure, LVEF at 6 months was significantly lower in African-Americans (p=0.02). A smaller left ventricular end-diastolic diameter (LVEDD; determined by transthoracic echocardiography) at first presentation was the strongest predictor of LVEF at 6 months (p<0.0001).

Myocardial Disease

The initially depressed left ventricular ejection fraction (LVEF) and HF symptoms improve in the majority of the ROCM patients under conventional HF treatment 2. However, chronic dilated cardiomyopathy (DCM) with persistently depressed LVEF and chronic HF can evolve 3. The mechanisms and factors responsible for the highly diverse evolution of ROCM, including myocarditis, are incompletely understood 4,5. The authors conclude that ROCM outcomes are generally favorable under contemporary HF medication, with rather lower than expected transplant free survival rates. Noticeably, the IMAC-2 trial reported a higher proportion of substantial LVEF improvement 10 EF units at 6 months (ca. 70%) compared to former studies (ca. 30-50%) 2, 6, 7, which indicates the efficacy of contemporary HF regimens, as well as the possibly higher adherence to treatment guidelines. Further major findings of the study are the adverse prognostic impact of higher LVEDD and of NYHA functional class IV at first presentation, and of African-American descent. In contrast, female gender was associated with improved outcome. These insights are consistent with the known better prognosis of women in heart failure 8, as well as with the known worse prognosis of African-Americans in HF 9, and the prognostic significance of LVEDD for myocardial recovery under assist device support 10. Thus, these demographic and echocardiographic data confirm that general CHF mechanisms equally apply to ROCM, and were undoubtedly important to be confirmed in this specific subgroup.

Acute myocarditis and DCM are etiopathogenically linked, mainly by persistence of cardiotropic viral infection and aberrant immune responses 3, 5. Comprehensive diagnostics of endomyocardial biopsies (EMB) have identified that the immunohistologically detected intramyocardial inflammation (as opposed to the histologically detected “active” or “borderline myocarditis”) 11-13 has adverse prognostic impact in AMC patients presenting with depressed LVEF 14. In selected patients, detection and persistence of viral genomes may be also relevant 15-17. These insights have been largely missed in the presented IMAC-2 trial, since EMB investigations were carried out in only 44 (12%) of the enrolled patients, and were subjected merely to histological evaluation, which revealed myocarditis in 10 (2.6%) subjects.

Furthermore, EMB investigations can be important for decision and timing of cardioverter-defibrillator (ICD) implantation 18. Of note, whilst the authors provide the information that n=28 (7.5%) patients had an ICD at study entry, no follow up data are presented for the ICDs implanted during follow up, which may be a surrogate or persistently depressed LVEF<35%. On the other hand, ICDs improve survival in HF patients substantially 19, and thus may have had substantial impact on prognosis in the IMAC-2 study, as well.

Late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) has been associated to adverse outcome in DCM 20, 21. It would have been highly interesting to access the prognostic value of LGE and possibly also further CMR data for the specific subgroup of ROCM patients in the IMAC-2 study.


  1. McNamara DM, Starling RC, Cooper LT, Boehmer JP, Mather PJ, Janosko KM, Gorcsan J, 3rd, Kip KE, Dec GW. Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated Cardiomyopathy Results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 Study. J Am Coll Cardiol 2011;58(11):1112-8.
  2. McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, Gass A, Janosko K, Tokarczyk T, Kessler P, Mann DL, Feldman AM. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001;103(18):2254-9.
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  7. Steimle AE, Stevenson LW, Fonarow GC, Hamilton MA, Moriguchi JD. Prediction of improvement in recent onset cardiomyopathy after referral for heart transplantation. J Am Coll Cardiol 1994;23(3):553-9.
  8. Hsich EM, Pina IL. Heart failure in women: a need for prospective data. J Am Coll Cardiol 2009;54(6):491-8.
  9. Yancy CW, Strong M. The natural history, epidemiology, and prognosis of heart failure in African Americans. Congest Heart Fail 2004;10(1):15-8; quiz 21-2.
  10. Simon MA, Primack BA, Teuteberg J, Kormos RL, Bermudez C, Toyoda Y, Shah H, Gorcsan J, 3rd, McNamara DM. Left ventricular remodeling and myocardial recovery on mechanical circulatory support. J Card Fail 2010;16(2):99-105.
  11. Noutsias M, Seeberg B, Schultheiss HP, Kühl U. Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 1999;99(16):2124-31.
  12. Grogan M, Redfield MM, Bailey KR, Reeder GS, Gersh BJ, Edwards WD, Rodeheffer RJ. Long-term outcome of patients with biopsy-proved myocarditis: comparison with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1995;26(1):80-4.

Notes to editor

Presented by:
Priv.-Doz. Dr. med. Michel Noutsias, Department of Cardiology, University Hospital of Marburg and Giessen / UKGM GmbH, Faculty of Medicine, Philipps-Universität Marburg, Baldinger Strasse 1, D-35043 Marburg, Germany.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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