Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy

Abstract

Background-In idiopathic dilated cardiomyopathy, there are scarce data on the influence of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance on left ventricular (LV) remodeling. Methods and Results-Fifty-eight consecutive patients with idiopathic dilated cardiomyopathy underwent baseline clinical, biohumoral, and instrumental workup. Medical therapy was optimized after study enrollment. Cardiovascular magnetic resonance was used to assess ventricular volumes, function, and LGE extent at baseline and 24-month follow-up. LV reverse remodeling (RR) was defined as an increase in LV ejection fraction ≥10 U, combined with a decrease in LV end-diastolic volume ≥10% at follow-up. ΔLGE extent was the difference in LGE extent between follow-up and baseline. LV-RR was observed in 22 patients (38%). Multivariate regression analysis showed that the absence of LGE at baseline cardiovascular magnetic resonance was a strong predictor of LV-RR (odds ratio, 10.857 [95% confidence interval, 1.844-63.911]; P=0.008) after correction for age, heart rate, New York Heart Association class, LV volumes, and LV and right ventricular ejection fractions. All patients with baseline LGE (n=26; 45%) demonstrated LGE at follow-up, and no patient without baseline LGE developed LGE at follow-up. In LGE-positive patients, there was an increase in LGE extent over time (P=0.034), which was inversely related to LV ejection fraction variation (Spearman ρ, −0.440; P=0.041). Five patients showed an increase in LGE extent >75th percentile of ΔLGE extent, and among these none experienced LV-RR and 4 had a decrease in LV ejection fraction ≥10 U at follow-up. Conclusions-In patients with idiopathic dilated cardiomyopathy, the absence of LGE at baseline is a strong independent predictor of LV-RR at 2-year follow-up, irrespective of the initial clinical status and the severity of ventricular dilatation and dysfunction. The increase in LGE extent during follow-up was associated with progressive LV dysfunction. (Circ Cardiovasc Imaging. 2013;6:790-799.)

Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure

“…Fibrosis has been regarded as a marker of disease severity, reflecting the burden of initial myocardial damage and subsequent injury because of adverse LV remodeling. 23 However, there are cumulating evidences supporting the knowledge that fibrosis is not a fixed marker of disease severity 24 but rather a dynamic process that may play a causative role in the progression of LVSD and ensuing onset of CHF. 25 Currently, risk stratification in patients with preclinical LVSD is primarily based on the degree of LVSD in the view of the fact that the likelihood of CHF and death augments with increasing the degrees of LVSD.…”

“…1,28 Risk stratification based on LV ejection fraction is also limited by the fact that more than one third of patients with NICM experiences a consistent and sustained improvement of LV ejection fraction after optimization of medical therapy irrespective of the severity of initial LV dilatation and dysfunction. 24,29 Thus, effective risk stratification remains challenging in NICM particularly in subjects without history of CHF also because of the paucity of the data in this specific subgroup of patients. A remarkable finding of our study is that the addition of presence or extent of LGE to clinical data alone or in combination with parameters of LV remodeling and function significantly improved the outcome prediction.…”

Response to Letters Regarding Article, “Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy: A Contrast-Enhanced Cardiovascular Magnetic Study”

“…3,4 In 7 explanted idiopathic dilated cardiomyopathy hearts, Gulati et al 4 showed an excellent agreement between replacement fibrosis at histopathology and LGE as seen with in vivo cardiovascular magnetic resonance. In our study, 5 we disregarded spotty LGE confined to the interventricular septum insertion points because whether this pattern identifies areas of fibrosis remains a matter of debate. For these reasons, we think that LGE in our patient population likely reflected replacement fibrosis.…”

Letter by Alter Regarding Article, “Myocardial Fibrosis as a Key Determinant of Left Ventricular Remodeling in Idiopathic Dilated Cardiomyopathy: A Contrast-Enhanced Cardiovascular Magnetic Study”

“…1 We have recently shown in 502 patients with DCM that LV dilatation is correlated with increased wall stress, which precedes the development of LV hypertrophy. 4 Because the ensuing hypertrophy is still inappropriate, greater dilatation is associated with wall stress increase.…”

“…Applying these findings to the referenced study, it has to be inferred that at time of enrollment LV wall stress was markedly increased in patients responding to initiation or intensification of heart failure treatment with a favorable remodeling, which is also reflected by the fact of increased N-terminal pro-brain natriuretic peptide as reported. 1 Brain natriuretic peptide correlates with ventricular wall stress. 5 Based on the reported LV mass and volume and using the wall stress index, it has to be assumed that LV end-diastolic and end-systolic wall stress was increased to 4.9 kPa versus 4.6 kPa (end-diastolic LV pressure assumed at 16 mm Hg, normal end-diastolic wall stress <4 kPa) and to 28.0 kPa versus 21.0 kPa (peripheral systolic pressure inserted as reported, normal endsystolic wall stress <18 kPa), respectively.…”