Ventricular Remodelling in CHF

• Drivers of structural remodelling:

  • depends on the underlying cause of heart failure (majority of chronic heart failures are due to acute myocardial infarction
  • drivers:
  • changed mechanical forces or pressure placed on the heart walls
  • ongoing neuroendocrine release
  • inflammatory mediators
• Structural changes (starts of good, but ends up bad):

  • ventricular dilation - becomes elongated
  • dysregulated ventricular hypertrophy - enlarged heart
  • capillary fibre mismatch -> fibrosis - scar tissue, not as strong as myocardial tissue and cannot conduct electrical activity
  • insufficient Ca2+ processes
  • myocyte apoptosis
  • fibroblastic activity -> fibrosis
• Remodelling Consequences:

  • systole:
  • loss of myocytes -> decrease in force generation & emptying difficulties
  • fibrosis -> interferes with force generation myocytes -> decrease in force generation & emptying difficulties
  • interference of Ca2+ processes -> force generating difficulties
  • ventricular dilation -> negative impact on force generation
• Remodelling Consequences:

  • diastole:
  • reduced compliance -> filling difficulties
  • significant hypertrophy -> decrease in fill volume
• Remodelling Consequences:

  • electrical:
  • fibrosis -> interferes with myocardial depolarisation -> predisposed to arrhythmias
  • erratic hypertrophy -> interferes with myocardial depolarisation -> predisposed to arrhythmias
• Degree of remodelling/maladaptive remodelling is variable, depending on:

  • cause of heart failure - e,g, mechanical or ischaemic
  • where due to acute myocardial infarction size
  • size of inflammatory response
  • presence of inflammation from cardiac/non-cardiac source ie presence of co-morbidities of an inflammatory nature
• Pathological Ventricular Remodelling in Heart Failure:

  • vicious cycle of events - culminating in degree of fibrosis, dysregulated hypertrophy, dilation, cell death, disrupted electrical excitation and contractile processes affecting force generation
  • in long term, the structurally failing heart is subject to ongoing negative neuroendocrine response -> perpetuate & escalation of some of the structural maladaptation -> negative neuroendocrine response
  • long term ongoing and remodelling of ventricle, ie passed the point of being beneficial compounds cardiac embarrassment, exacerbates heart failure and escalates disability
  • switching off/dampening some endocrine responses that are drives of structural maladaptation is a drug therapy goal