Andrea Barison

Progression of Myocardial Fibrosis Assessed With Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy

OBJECTIVES This study sought to assess the rate of progression of fibrosis by 2 consecutive cardiac magnetic resonance (CMR) examinations and its relation with clinical variables. BACKGROUND In hypertrophic cardiomyopathy (HCM) myocardial fibrosis, detected by late gadolinium enhancement (LGE), is associated to a progressive ventricular dysfunction and worse prognosis. METHODS A total of 55 HCM patients (37 males; mean age 43 ± 18 years) underwent 2 CMR examinations (CMR-1 and CMR-2) separated by an interval of 719 ± 410 days. Extent of LGE was measured, and the rate of progression of LGE (LGE-rate) was calculated as the ratio between the increment of LGE (in grams) and the time (months) between the CMR examinations. RESULTS At CMR-1, LGE was detected in 45 subjects, with an extent of 13.3 ± 15.2 g. At CMR-2, 53 (96.4%) patients had LGE, with an extent of 24.6 ± 27.5 g. In 44 patients, LGE extent increased significantly (≥1 g). Patients with apical HCM had higher increments of LGE (p = 0.004) and LGE-rate (p < 0.001) than those with other patterns of hypertrophy. The extent of LGE at CMR-1 and the apical pattern of hypertrophy were independent predictors of the increment of LGE. Patients with worsened New York Heart Association functional class presented higher increase of LGE (p = 0.031) and LGE-rate (p < 0.05) than those with preserved functional status. CONCLUSIONS Myocardial fibrosis in HCM is a progressive and fast phenomenon. LGE increment, related to a worse clinical status, is more extensive in apical hypertrophy than in other patterns.

Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling

AIMS To assess the intricate relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodelling. METHODS AND RESULTS A cohort of 260 reperfused ST-segment elevation MI patients was prospectively studied with cardiovascular magnetic resonance at 1 week (baseline) and 4 months (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late-gadolinium enhancement imaging, respectively. Adverse LV remodelling was defined as an increase in LV end-systolic volume ≥15% at follow-up. One hundred and twenty-seven (49%) patients had anterior MI and 133 (51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (P = 0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodelling (P = 0.017) and lower LV ejection fraction (EF) at follow-up (P = 0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis, baseline MI size but not its location was an independent predictor of adverse LV remodelling (odds ratio = 1.061, P < 0.001) and EF at follow-up (β-coefficient = -0.255, P < 0.001). CONCLUSION Anterior MI patients experience more pronounced post-infarction LV remodelling and dysfunction than non-anterior MI patients due to a greater magnitude of irreversible ischaemic LV damage without any independent contribution of MI location.

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

Background—We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non–ischemic cardiomyopathy without history of congestive heart failure (CHF). Methods and Results—At 3 tertiary referral centers, 228 patients with non–ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78–9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61–10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66–41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08–7.76]; P<0.001). Improvement &khgr;2 analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). Conclusions—In patients with non–ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.

Myocardial delayed enhancement in paucisymptomatic nonischemic dilated cardiomyopathy.

OBJECTIVES We investigated the prognostic role of myocardial fibrosis by delayed enhancement (DE) cardiovascular magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (NICM) patients with no or mild symptoms of heart failure (HF). METHODS A prospective cohort of 125 NICM patients (82 males, age 59±14years, mean±SD) with echocardiographic evidence of left ventricular (LV) systolic dysfunction (mean ejection-fraction 33±10%), without (stage B) or with history of mild HF symptoms (stage C, NYHA classes I-II) was enrolled. The end-point was a composite of cardiac death and HF hospitalization. RESULTS Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass. During a median follow-up of 14.2months, 16 (32%) patients with DE experienced a composite event versus only 6 (8%) patients without DE (Kaplan-Meier survival curve, p=0.001). After correction for age, CMR-derived LV and right ventricular volumes, echocardiographic measurements of LV diastolic function and Doppler-estimated systolic pulmonary artery pressure, the presence of DE remained a strong and independent predictor of cardiac death or HF hospitalization (hazard ratio: 5.32, 95% confidence intervals 1.60 to 17.63, p=0.006). CONCLUSIONS In NICM patients with no or mild HF symptoms, the presence of myocardial DE is a strong predictor of worse clinical outcome even after correction for other established prognostic determinants. Contrast-enhanced CMR may be useful in prognostic stratification from the early stages of NICM.

Markers of fibrosis, inflammation, and remodeling pathways in heart failure

Ventricular remodeling occurs progressively in untreated patients after large myocardial infarction and in those with cardiomyopathy. The pathologic changes of increased left ventricular (LV) volume and perturbation in the LV chamber geometry involve not only the myocytes, but also the non-myocyte cells and the extracellular matrix. Inflammation, fibrosis, neuro-hormonal activation, and ongoing myocardial damage are the mechanisms underlying remodeling. The detection of an ongoing remodeling process by means of biomarkers such as cytokines, troponins, neurohormones, metalloproteinases, galectin-3, ST-2 and others, may hold a clinical value and could, to some extent, drive the therapeutical strategy in patients after a myocardial infarction or with heart failure. For this reason, there is an increasing interest in the development of new biomarkers and a great number of laboratory tests have been recently proposed, whose clinical usefulness, however, is not fully established yet.

Prognostic significance of myocardial extracellular volume fraction in nonischaemic dilated cardiomyopathy

Aims In nonischaemic dilated cardiomyopathy (NICM), replacement myocardial fibrosis as detected by late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) is associated with poor prognosis. We investigated the as-yet unexplored prognostic significance of interstitial fibrosis in NICM, using T1-mapping CMR. Methods Eighty-nine NICM patients (63 men, age 59 ± 14 years) with left ventricular systolic dysfunction (ejection fraction 41 ± 13%) underwent comprehensive clinical and CMR evaluation, with extracellular volume fraction (ECV) estimation from pre and postcontrast T1 mapping. Fifteen healthy individuals (11 men, mean age 52 ± 11 years) were used as controls. The end-point was a composite of cardiovascular death, hospitalization for heart failure and appropriate defibrillator intervention. Results Myocardial ECV was higher in NICM patients (0.31 ± 0.05) than controls (0.25 ± 0.04, P < 0.01). In NICM patients, myocardial ECV correlated with left ventricular ejection fraction (R2 = 0.13), LGE extent (R2 = 0.17), Doppler E/E′ (R2 = 0.17) and ventricular tachycardias (R2 = 0.21) at 24-h ECG monitoring (P < 0.05 for all). During a median follow-up of 24 months (interquartile range 12–42 months), 12 events occurred and higher myocardium ECV was independently associated with the occurrence of the composite end-point (P < 0.01). Conclusion In NICM patients, myocardial ECV was increased compared with normal individuals, likely reflecting extracellular matrix remodelling and collagen deposition, and resulted an independent prognostic predictor beyond all other conventional clinical, electrocardiographic and echocardiographic parameters.

Galectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy☆

BACKGROUND Left ventricular (LV) fibrosis, assessed by late gadolinium enhancement (LGE) at cardiac magnetic resonance imaging (MRI), is a marker of LV remodeling, and holds prognostic value in nonischemic dilated cardiomyopathy (NICM). Galectin-3 has been shown to participate in tissue fibrogenesis and to be a prognosticator in heart failure. Our aim was to investigate the relationships between galectin-3 circulating level and myocardial fibrosis at MRI in patients with NICM. METHODS AND RESULTS One-hundred-fifty patients were enrolled (males 73%; age 58, SD 14 years), with a NICM diagnosis according to the World Health Organization criteria. All patients underwent a comprehensive clinical assessment and biohumoral characterization, including galectin-3 assay, and cardiac MRI, with LGE assessment of fibrosis. Median galectin-3 value was 14.4 ng/mL (IQR 11.7-19.0 ng/mL), and LGE was detected in 106 (71%) patients. Patients with LGE had higher galectin-3 than those without (15.4, 11.8-21.0, vs 13.1, 11.7-16.4 ng/mL, p=0.006). Among univariate predictors of LGE presence (galectin-3, male sex, disease duration, arterial hypertension, left and right ventricular ejection fraction, left ventricular stroke volume), galectin-3 maintained its predictive value at multivariate analysis, together with sex, hypertension, disease duration and right ventricular ejection fraction. At receiver operating characteristic analysis the optimal galectin-3 cut-off for LGE prediction was 14.6 ng/mL (AUC 0.651, sensitivity 57%, specificity 73%). CONCLUSIONS Galectin-3 is associated with LGE-assessed myocardial replacement fibrosis in patients with NICM. These results support the hypothesis that galectin-3 is involved in cardiac fibrosis and remodeling in NICM, and that its assay may help to select subgroups at higher risk.

CMR-verified interstitial myocardial fibrosis as a marker of subclinical cardiac involvement in LMNA mutation carriers.

Lamin A/C ( LMNA ) gene mutation, identified in 10% of familial dilated cardiomyopathy (DCM) patients, is associated with an increased risk of sudden cardiac death (SCD), which may be the first clinical manifestation ([1][1]). Myocardial fibrosis (MF) has been identified in the hearts of LMNA

Reference values of cardiac volumes, dimensions, and new functional parameters by MR: A multicenter, multivendor study.

To define reference values of cardiac volumes, dimensions, and new morpho‐functional parameters normalized for age, gender, and body surface area by cine‐bSSFP (balanced steady‐state free‐precession) magnetic resonance (MR).

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging

Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity.