Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography

Eur Heart J. 2012 Mar;33(5):640-8. doi: 10.1093/eurheartj/ehr391. Epub 2011 Nov 1.

Abstract

Aims: To determine whether the extent of myocardial fibrosis by late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), and echocardiographic ventricular dyssynchrony are independently associated with response to medical therapy in patients with newly diagnosed idiopathic dilated cardiomyopathy (DCM). Myocardial fibrosis and ventricular dyssynchrony are frequent findings in DCM. Previous studies focused on patients with established cardiomyopathy; however, the degree of myocardial fibrosis and ventricular dyssynchrony at presentation and their role in perpetuating left ventricular (LV) dysfunction in DCM remains unclear. Those studies of individuals with long-standing DCM did not characterize patients early in the disease course, and may not have included those with significant improvement in LV function. Thus factors contributing to LV recovery are uncertain.

Methods and results: Consecutive patients with a new diagnosis of DCM [LV ejection fraction (EF) ≤45%] made within the preceding 2 weeks were recruited. Patients underwent LGE-CMR, echocardiography, 6-minute walk testing, cardiopulmonary exercise testing, and blood sampling for measurement of serum amino-terminal pro-brain natiuretic peptide (NT-pro-BNP) concentration at baseline. Baseline patient characteristics were compared with a cohort of healthy volunteers. Myocardial fibrosis by LGE-CMR was quantified, identified by experienced observers blinded to patient outcome. Left ventricular systolic function was reassessed after 5 months of optimal medical therapy. Sixty-eight patients with DCM and 19 healthy volunteers were studied. DCM patients were studied a median 12.5 days following diagnosis. Compared with healthy controls, DCM patients exhibited greater inter- and intra-ventricular dyssynchrony. Twenty-four per cent of DCM patients exhibited LGE at diagnosis. Among DCM patients with LGE, the mean fibrosis mass was 2.2 ± 1.3 g. On multivariate analysis, strain dyssynchrony index, and fibrosis mass were independently associated with change in the LVEF over time (P≤ 0.001). Late-gadolinium enhancement cardiovascular magnetic resonance conferred additive value for modelling change in the LVEF beyond clinical and echocardiographic dyssynchrony parameters.

Conclusion: The extent of myocardial fibrosis is independently associated with lack of response to medical therapy in new-presentation DCM, and LGE-CMR may thus be an important risk-stratifying investigation in these patients. Accurate risk stratification may permit more targeted pharmacological and device therapies for patients with newly diagnosed DCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology
  • Case-Control Studies
  • Contrast Media
  • Echocardiography, Doppler, Color
  • Exercise Test
  • Female
  • Fibrosis / pathology
  • Fibrosis / physiopathology
  • Gadolinium DTPA
  • Heart Failure / drug therapy
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Humans
  • Magnetic Resonance Angiography
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Myocardium / pathology*
  • Observer Variation
  • Stroke Volume / physiology
  • Treatment Outcome
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Contrast Media
  • Mineralocorticoid Receptor Antagonists
  • Gadolinium DTPA