Ventricular remodeling
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Ventricular Remodeling |
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Differentiating Ventricular Remodeling From Other Conditions |
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Diagnosis |
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Treatment |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor-in-Chief: Mohammad I. Barouqa, M.D.
Synonyms and keywords: Left ventricular remodeling, LV remodeling
Overview
The Left Ventricle has an enormous ability to respond to any type of stress or pathological process. Such a response includes a complex a wide range of transcriptional, signaling, structural, electrophysiological and functional events of cardiac myocytes as well as other cells within the ventricle.
Ventricular remodeling is classified as Pathological or Physiological.
Historical Perspective
Classification
Ventricular remodeling can be either physiological or pathological. Physiological changes occur in cases of pregnancy, exercise and post-natal growth and considered to be normal, whereas pathological remodeling occur due to cardiac injury and can end up with cardiac arrhythmia and heart failure.
Remodeling has three patterns. Concentric remodeling where there is an increase in relative wall thickness (Ventricular wall thickness compared to cavity size) and with or without increase cardiac mass.This change is noticed in cases of pressure overload.Eccentric Hypertrophy where there is an increase in cardiac mass and chamber volume with relative wall thickness varying between being decreased, the same or increased. This change is noticed in cases of volume overload, after infarction and isotonic exercise. Mixed Concentric and Eccentric changes as in Myocardial Infarction (MI), Where there is a combined volume and pressure overload on noninfarcted areas.
Remodeling can be classified as adaptive or maladaptive.
Pathophysiology
Causes
Differentiating Ventricular remodeling from other Diseases
Epidemiology and Demographics
Maladaptive remodeling is age dependent and the mortality rate resulting from Myocardial Infarction increases with age.
Coronary artery disease which is the leading cause of heart failure with reduced systolic function occurs more in males than females.However, heart failure with preserved systolic function affects females more than males with a ratio of 2:1.
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Future or Investigational Therapies
ACE inhibitors and ARBs used to treat hypertension have the ability to target cardiac remodeling and reduce heart failure morbidity and mortality. Recent studies targeted Renin, the rate limiting step of Angiotensin II production, using Aliskiren and showed an ability to blunt cardiac remodeling in infarcted mice hearts. The addition of Mineralocorticoid Receptors Antagonists (MRA) in low doses revealed that there is an improvement in the symptoms of patients with moderately severe or severe heart failure,especially those of recent decompensation or left ventricular dysfunction early after infarction.Spironolactone and Eplerenone are among the MRA drugs used. However, Spironolactone has adverse metabolic and endocrine side effects making eplerenone use to become more convenient.MRA therapy can lead to an increased level of aldosterone,which in its turn can lead to deleterious effects on the heart through non-mineralocorticoid receptors.
β-adrenergic receptor blockers are also among drugs used treat hypertension, cardiac arrhythmias and cardiac remodeling. Cardiac myocytes express β1 receptors and respond to β1-selective inhibitors.Nevertheless, fibroblasts express β2-receptors making the mechanism to which β-blockers act to become indefinable.
Positive inotropic agents used to control symptoms in decompensated heart failure showed to have an increase in mortality over the long term, and the use of Digoxin did not affect the mortality rate in the long run. However, two new nonglycoside inotropic agents are studied more thoroughly now.One is to deliver cDNA of the sacroplasmic reticulum Ca2+ pump via an Adeno-associated virus in order to refill the downregulated sacroplasmic reticulum Ca2+ levels and showed safety and benefits in advanced heart failure. The second is a Luso-inotropic compound, Istaroxime, which inhibits Na/K ATPase that can lead to accumulation of Na+ intracellulary and decrease the activity of Na-Ca ions exchanger to remove cystolic Ca2+, and hence activates the sacromeric contraction. This process showed a decrease in capillary wedge pressure and heart rate during phase II clinical trial.
HMG-CoA reductase inhibitors originally used to lower cholesterol level can provide protection to patients with ischemic heart disease. And anti-remodeling effects can occur when they are added to ACE inhibitors and β-blockers.
Vasopressin receptor antagonists such as conivaptan, Lixivaptan, Mozavaptan and Tolvaptan showed no effect on Heart failure long-term mortality and morbidity when used for acute treatment of hospitalized Heart failure patients. However, the addition of Tolvaptan in its oral form to standard therapy improved the symptoms of some Heart failure patients without series cardiac events.
Stem cells being considered for myocardial regeneration can be derived from bone marrow , circulating pools of progenitor cells and tissue-resident stem cells derived from adipose tissue, skeletal muscle ,myocardium and epicardium.The majority of clinical trials using stem cells derived from bone marrow showed safety and benefits in the treatment of ischemic heart disease beyond the standard therapy.However,some studies did not show any efficacy as patients receiving autologous adult stem cells are in advanced age and with different comorbidities such as hypertension and diabetes mellitus.Such comorbidities have effects on the viability of stem cells.