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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    • "Limitations of the conventional research paradigm are clearly reflected by the limited number of areas of relative success in heart failure treatment, such as angiotensin converting enzyme inhibitors, β-blockers, aldosterone antagonists, coronary revascularization, heart transplantation, and mechanical devices. While it is true that description of remodelling after myocardial infarction, for example, was first deciphered from experimental work in rodents by Pfeffer and Braunwald [22] (showing that there was a dynamic process post-myocardial infarction that was amenable to being altered in rodents) and was subsequently confirmed in human patients [23] such studies are the exception, not the norm. In reality, the vast majority of basic science experiments have not provided valuable insight into the limited success in heart failure treatment seen to date. "
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    ABSTRACT: Heart failure remains a leading cause of death and it is a major cause of morbidity and mortality affecting tens of millions of people worldwide. Despite decades of extensive research conducted at enormous expense, only a handful of interventions have significantly impacted survival in heart failure. Even the most widely prescribed treatments act primarily to slow disease progression, do not provide sustained survival advantage, and have adverse side effects. Since mortality remains about 50% within five years of diagnosis, the need to increase our understanding of heart failure disease mechanisms and development of preventive and reparative therapies remains critical. Currently, the vast majority of basic science heart failure research is conducted using animal models ranging from fruit flies to primates; however, insights gleaned from decades of animal-based research efforts have not been proportional to research success in terms of deciphering human heart failure and developing effective therapeutics for human patients. Here we discuss the reasons for this translational discrepancy which can be equally attributed to the use of erroneous animal models and the lack of widespread use of human-based research methodologies and address why and how we must position our own species at center stage as the quintessential animal model for 21(st) century heart failure research. If the ultimate goal of the scientific community is to tackle the epidemic status of heart failure, the best way to achieve that goal is through prioritizing human-based, human-relevant research.
    American Journal of Translational Research 11/2015; 7(9):1636-47. · 3.40 Impact Factor
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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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