Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction

Sutton, Martin St. John; Lee, Douglas S.; Rouleau, Jean L.; Goldman, Steven; Plappert, Ted; Braunwald, Eugene; Pfeffer, Marc A.

doi:10.1161/01.cir.0000070420.51787.a8

Cited by 212 publications

(119 citation statements)

References 37 publications

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“…[2][3][4][5][6] At the infarcted region, alterations in myocardial composition and structure occur after MI 6,7 and can lead to infarct thinning and expansion. 1,4 -7 Because the MMPs are enzymes that influence myocardial remodeling, 8 -16 the goal of the present study was to examine the relation between MMP activation and infarct expansion.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] The summation of cellular and extracellular events that occur in the post-MI period results in changes in LV geometry and has been called "infarct expansion." [3][4][5][6] Past studies have demonstrated that a structural determinant of infarct expansion is extracellular remodeling. 1,5,6 A family of proteolytic enzymes that have been implicated in tissue remodeling are the matrix metalloproteinases (MMPs).…”

mentioning

confidence: 99%

“…[3][4][5][6] Past studies have demonstrated that a structural determinant of infarct expansion is extracellular remodeling. 1,5,6 A family of proteolytic enzymes that have been implicated in tissue remodeling are the matrix metalloproteinases (MMPs). 7 Increased MMP expression has been reported in patients with end-stage heart failure and in several animal models of developing LV dysfunction.…”

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confidence: 99%

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Myocardial Infarct Expansion and Matrix Metalloproteinase Inhibition

et al. 2003

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Background-A potential mechanism for left ventricular (LV) remodeling after myocardial infarction (MI) is activation of the matrix metalloproteinases (MMPs). This study examined the effects of MMP inhibition (MMPi) on regional LV geometry and MMP levels after MI. Methods and Results-In pigs instrumented with radiopaque markers to measure regional myocardial geometry, MI was created by ligating the obtuse marginals of the circumflex artery. In the first study, pigs were randomized to MMPi (nϭ7; PD166793, 20 mg · kg Ϫ1 · d Ϫ1 ) or MI only (nϭ7) at 5 days after MI, and measurements were performed at 2 weeks. Regional MI areas were equivalent at randomization and were increased in the MI-only group at 2 weeks after MI compared with the MMPi group. In the second study, pigs randomized to MMPi (nϭ9) or MI only (nϭ8) were serially followed up for 8 weeks. At 8 weeks after MI, LV end-diastolic dimension was lower with MMPi than in the MI-only group (4.7Ϯ0.1 versus 5.1Ϯ0.1 cm, PϽ0.05). Regional MI area was reduced with MMPi at 8 weeks after MI (1.3Ϯ0.1 versus 1.7Ϯ0.1 cm 2 , PϽ0.05). MMPi reduced ex vivo MMP proteolytic activity. In the MI region, membrane-type MMP levels were normalized and levels of the endogenous tissue inhibitor of MMPs (TIMP-1) were increased compared with normal levels with MMPi. These effects were not observed in the MI-only group. Conclusions-MMPi

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confidence: 99%

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Myocardial Infarct Expansion and Matrix Metalloproteinase Inhibition

et al. 2003

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“…Remodeling is linked to heart failure progression and is associated with poor prognosis following myocardial infarction. Ventricular dilation following myocardial infarction is an important predictor of mortality [6] and adverse cardiac events [7], including the development of heart failure and ventricular arrhythmias [8], [9]. The extent of adverse remodeling depends on the size of the infarct but is also directly affected by the pathologic and structural changes associated with infarct healing.…”

Section: Introductionmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

568

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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“…LV diameter has been shown to be independently predictive of SCA and to have an additive effect with LVEF on predicting SCA risk 34, 35. Two studies, 1 in patients post–myocardial infarction36 and the other in patients with severe LV dysfunction,37 found that increased LV size was predictive of ventricular arrhythmias and frequent premature ventricular contractions (PVC). This association was further supported in a study that found reduction of LV end‐systolic size in patients undergoing cardiac resynchronization therapy reduced occurrence of PVCs and VT/VF events 38.…”

Section: Discussionmentioning

confidence: 99%

Left Ventricular Geometry and Risk of Sudden Cardiac Arrest in Patients With Severely Reduced Ejection Fraction

Phan

Aro

Reinier

et al. 2016

JAHA

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BackgroundRecent reports indicate that specific left ventricular (LV) geometric patterns predict recurrent ventricular arrhythmias in patients with implantable cardioverter‐defibrillators and reduced left ventricular ejection fraction (LVEF). However, this relationship has not been evaluated among patients at risk of sudden cardiac arrest (SCA) in the general population.Methods and ResultsAdult SCA cases from the Oregon Sudden Unexpected Death Study were compared with geographic controls with no prior history of SCA. Archived echocardiograms performed closest and prior to the SCA event were reviewed. LV geometry was defined as normal (normal LV mass index [LVMI] and relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT), or eccentric hypertrophy (increased LVMI and normal RWT). Analysis was restricted to those with LVEF ≤40%. A total of 246 subjects were included in the analysis. SCA cases (n=172, 68.6±13.3 years, 78% male), compared to controls (n=74, 66.8±12.1 years, 73% male), had lower LVEF (29.4±7.9% vs 30.8±6.3%, P=0.021). Fewer cases presented with normal LV geometry (30.2% vs 43.2%, P=0.048) and more with eccentric hypertrophy (40.7% vs 25.7%, P=0.025). In a multivariate model, eccentric hypertrophy was independently predictive of SCA (OR 2.15, 95% CI 1.08–4.29, P=0.03).ConclusionsEccentric LV hypertrophy was independently associated with increased risk of SCA in subjects with EF ≤40%. These findings, now consistent between device‐implanted and non‐implanted populations, indicate the potential of improving SCA risk stratification from the same noninvasive echocardiogram at no additional cost.

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Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction

Cited by 212 publications

References 37 publications

Myocardial Infarct Expansion and Matrix Metalloproteinase Inhibition

Myocardial Infarct Expansion and Matrix Metalloproteinase Inhibition

The immune system and cardiac repair

Left Ventricular Geometry and Risk of Sudden Cardiac Arrest in Patients With Severely Reduced Ejection Fraction

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