Quiz

• What initiates cardiac muscle contraction?

  An action potential reaches the sarcolemma
• What do L-type calcium channels allow during cardiac contraction?

  Extracellular calcium (Ca²⁺) to enter
• What triggers calcium-induced calcium release (CICR)?

  A small influx of calcium from outside
• What binds to troponin C during muscle contraction?

  Elevated calcium
• What is the role of troponin and tropomyosin in muscle contraction?

  They expose actin binding sites
• What is the process called that links excitation to contraction in cardiac muscle?

  Excitation-contraction coupling
• How does heart failure affect excitation-contraction coupling?

  It impairs the process due to reduced SERCA2a activity
• What does reduced SERCA2a activity lead to in heart failure?

  Limits calcium reuptake into the SR
• What is the effect of increased Na⁺/Ca²⁺ exchanger (NCX) activity in heart failure?

  Extrudes more calcium from the cell
• How do changes in calcium handling affect cardiac function in heart failure?

  They weaken systolic function and reduce output
• What compensatory mechanism is activated in heart failure?

  The sympathetic nervous system (SNS)
• What does chronic SNS activation lead to in heart failure?

  Calcium mishandling and β-receptor desensitization
• What happens to diastolic calcium levels in heart failure?

  Calcium leakage from the SR reduces availability
• What system is upregulated in response to reduced renal perfusion in heart failure?

  The renin-angiotensin-aldosterone system (RAAS)
• What does renin convert angiotensinogen into?

  Angiotensin I
• What is the role of angiotensin II (Ang II) in heart failure?

  Promotes cardiac remodelling and fibrosis
• Which pathways does Ang II activate to promote fibrosis?

  Gq/PLC/IP3/DAG and MAPK pathways
• What does TGF-β/SMAD signalling drive in heart failure?

  Fibrosis
• What effect does antidiuretic hormone (ADH) have in heart failure?

  Promotes water retention and fluid overload
• What is the role of atrial natriuretic peptide (ANP) in heart failure?

  Induces natriuresis and vasodilation
• Why are ANP effects often insufficient in heart failure?

  Due to RAAS overactivation
• What is the mechanism of action of Entresto?

  • Angiotensin receptor-neprilysin inhibitor (ARNI)
  • Counteracts SNS and RAAS activation
  • Prevents cardiac remodelling
• What does valsartan do in the context of heart failure?

  Blocks the AT1 receptor
• What is the effect of AT1 receptor blockade?

  Reduces Ang II binding to AT1
• What does AT2 receptor activation promote?

  Nitric oxide (NO) release and vasodilation
• What does sacubitril inhibit?

  Neprilysin
• What is the effect of preventing neprilysin breakdown?

  Increases levels of natriuretic peptides
• What do natriuretic peptides activate?

  Natriuretic peptide receptors (NPR-A, NPR-B)
• What is the result of cGMP-PKG signalling activation?

  Opposes MAPK activation and improves relaxation
• What are the clinical benefits of Entresto shown in the PARADIGM-HF trial?

  Reduces cardiovascular mortality and hospitalizations
• How does Entresto improve left ventricular ejection fraction (LVEF)?

  By inhibiting maladaptive intracellular pathways
• What does Entresto do to ventricular wall stress?

  Reduces ventricular wall stress
• How does Entresto affect myocardial ATP production?

  Enhances myocardial ATP production
• What is the overall effect of Entresto on heart failure progression?

  Slows heart failure progression