Article

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

Tufts University, Бостон, Georgia, United States
JACC. Cardiovascular imaging (Impact Factor: 6.99). 01/2011; 4(1):98-108. DOI: 10.1016/j.jcmg.2010.10.008
Source: PubMed

ABSTRACT 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 · 3.86 Impact Factor
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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; 10:35. DOI:10.1186/1476-9255-10-35 · 2.22 Impact Factor
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    • "The major new finding of the present study is that myocardial remodeling, as well as bioelectric changes in tachycardia-induced HF, support an important role of remodeling in HF progression (17). Several possible explanations can account for the observed results in myocardial electrical and mechanical remodeling (4-9). The dogs subjected to rapid pacing developed persistent tachycardia, which resulted in low-output HF characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility (4-9). "
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    ABSTRACT: In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 09/2013; DOI:10.1590/1414-431X20132694 · 1.08 Impact Factor
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