Left Ventricular Remodeling in Heart Failure Current Concepts in Clinical Significance and Assessment

Tufts University, Бостон, Georgia, United States
JACC. Cardiovascular imaging (Impact Factor: 7.19). 01/2011; 4(1):98-108. DOI: 10.1016/j.jcmg.2010.10.008
Source: PubMed


Ventricular remodeling, first described in animal models of left ventricular (LV) stress and injury, occurs progressively in untreated patients after large myocardial infarction and in those with dilated forms of cardiomyopathy. The gross pathologic changes of increased LV volume and perturbation in the normal elliptical LV chamber configuration is driven, on a histologic level, by myocyte hypertrophy and apoptosis and by increased interstitial collagen. Each of the techniques used for tracking this process-echocardiography, radionuclide ventriculography, and cardiac magnetic resonance-carries advantages and disadvantages. Numerous investigations have demonstrated the value of LV volume measurement at a single time-point and over time in predicting clinical outcomes in patients with heart failure and in those after myocardial infarction. The structural pattern of LV remodeling and evidence of scarring on cardiac magnetic resonance have additional prognostic value. Beyond the impact of abnormal cardiac structure on cardiovascular events, the relationship between LV remodeling and clinical outcomes is likely linked through common local and systemic factors driving vascular as well as myocardial pathology. As demonstrated by a recent meta-analysis of heart failure trials, LV volume stands out among surrogate markers as strongly correlating with the impact of a particular drug or device therapy on patient survival. These findings substantiate the importance of ventricular remodeling as central in the pathophysiology of advancing heart failure and support the role of measures of LV remodeling in the clinical investigation of novel heart failure treatments.

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    • "Therefore, understanding how macrophage and fibroblast form and function within the MI region are affected following targeted CHAM injections remains a critical issue if these biomaterials are to continue advancement as a possible therapeutic for post-MI remodeling. Past studies have identified that critical time points of post-MI remodeling in terms of infarct expansion and structural changes within the MI region occur at 7 and 21 days post-MI (Ertl and Frantz, 2005; Spinale, 2007; Konstam et al., 2011; Frangogiannis, 2012). Accordingly, LV geometry and function, indices of ECM remodeling, as well as studies of isolated of macrophages and fibroblasts were performed at these post-MI time points to define specific phenotypic changes in these cell types with respect to CHAM injections. "
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    ABSTRACT: A treatment target for progressive LV remodeling prevention following myocardial infarction (MI) is to affect structural changes directly within the MI region. One approach is through targeted injection of biocomposite materials, such as calcium hydroxyapatite (CHAM), into the MI region. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage (MAC) and fibroblast (FIBRO), were examined. MI was induced in adult pigs before randomization to CHAM injections (20, 0.1mL, targeted injections within MI region) or saline. At 7 or 21 days post-MI (n=6/time point/group), cardiac MRI was performed, followed by MAC and FIBRO isolation. Isolated MAC profiles for monocyte chemotactic MAC inflammatory protein-1 (MCP-1) as measured by rtPCR increased at 7 days post-MI in the CHAM group compared to MI only (16.3+6.6 vs 1.7+0.6 Ct values, p<0.05) and were similar by 21 days post-MI. Temporal changes in FIBRO function and smooth muscle actin (SMA) expression relative to referent control (n=5) occurred with MI. CHAM induced increases in FIBRO proliferation, migration, and SMA expression - indicative of FIBRO transformation. By 21 days, CHAM reduced LV dilation (diastolic volume: 75+2 vs 97+4 mL) and increased function (ejection fraction: 48+2 vs 38+2 %) compared to MI only (both p<0.05). This study identified that effects on macrophage and fibroblast differentiation occurred with injection of biocomposite material within the MI, which translated into reduced adverse LV remodeling. These unique findings demonstrate biomaterial injections impart biological effects upon the MI remodeling process over any biophysical effects.
    Journal of Pharmacology and Experimental Therapeutics 07/2014; 350(3). DOI:10.1124/jpet.114.215798 · 3.97 Impact Factor
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    • "Non-invasive imaging techniques play a major role in the early identification of myocardial viability , in localization of muscle damage, and extent of LV remodeling. Using novel imaging methods in patients with MI and / or heart failure, one can have better understanding of the LV remodeling patterns and their underlying etiology and outcome[6]. Echocardiography is a fast and simple noninvasive imaging method, and thus represents the preferred imaging tool to quantify the LV remodeling [9]. "
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    ABSTRACT: Myocardial infarction (MI) or acute myocardial infarction (AMI) commonly known as heart attack is one of the major causes of cardiac death worldwide. It occurs when the blood supply to the portion of the heart muscle is blocked or stopped causing death of heart muscle cells. Early detection of MI will help to prevent the infarct expansion leading to left ventricle (LV) remodeling and further damage to the cardiac muscles. Timely identification of MI and the extent of LV remodeling are crucial to reduce the time taken for further tests, ...
    IEEE Reviews in Biomedical Engineering 06/2014;
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    • "It involves a continuum of changes in the structure and function of the myocardium that usually occur in cardiac hypertrophy (CH) and heart failure (HF) as a result of pathological processes [2]. Chronic hypertension, congenital heart disease with intracardiac shunting, and cardiac valvular disease may also lead to heart remodelling [3,4]. However, we identified a new agent in addition to common injury that could result in myocardial remodelling. "
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    ABSTRACT: The epigenetic plasticity hypothesis indicates that pregnancy exposure may result in adult-onset diseases, including hypertension, diabetes and cardiovascular disease, in offspring. In a previous study, we discovered that prenatal exposure to inflammatory stimulants, such as lipopolysaccharides (LPS), could lead to hypertension in adult rat offspring. In the present study, we further demonstrate that maternal inflammation induces cardiac hypertrophy and dysfunction via ectopic over-expression of nuclear transcription factor κB (NF- κB), and pyrrolidine dithiocarbamate (PDTC) can protect cardiac function by reducing maternal inflammation. Pregnant SD rats were randomly divided into three groups and intraperitoneally injected with a vehicle, LPS (0.79 mg/kg), or LPS (0.79 mg/kg) plus PDTC (100 mg/kg) at 8 to 12 days of gestation. The offspring were raised until 4 and 8 months old, at which point an echocardiographic study was performed. The left ventricular (LV) mass index and apoptosis were examined. At 4 months of age, the LPS offspring exhibited augmented posterior wall thickness. These rats displayed left ventricle (LV) hypertrophy and LV diastolic dysfunction as well as a higher apoptotic index, a higher level of Bax and a lower level of Bcl-2 at 8 months of age. The protein levels of NF-κB (p65) in the myocardium of the offspring were measured at this time. NF-κB protein levels were higher in the myocardium of LPS offspring. The offspring that were prenatally treated with PDTC displayed improved signs of blood pressure (BP) and LV hypertrophy. Maternal inflammation can induce cardiac hypertrophy in offspring during aging accompanied with hypertension emergence and can be rescued by the maternal administration of PDTC (the inhibitor of NF-κB).
    Journal of Inflammation 11/2013; 10(1):35. DOI:10.1186/1476-9255-10-35 · 2.02 Impact Factor
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