Lecture 6 LV Dysfunction and Heart Failure II Flashcards
What is significant about the target for therapeutics in heart failure
Therapeutics don’t target the heart itself but the compensatory response that the body triggers
The compensatory mechanism triggered by a drop in cardiac out during heart failure can be divided into the two regions it effects. What are these
Cardiac – effects on the heart itself, system – effects on the vasculature and other organs
Why is the compensatory mechanism triggered in heart failure often derogatory
Heart attacks are a relatively recent occurrence, only seen in the last 200 years. As such the body hasn’t evolved to deal with it appropriately. However a number of the changes that occur during heart failure are similar to what is seen during blood loss, something which the body has adapted to. As such the body notices the decrease in cardiac output and other changes occurring during heart failure and wrongly assumes this is due to blood loss. This is why the neurohumoral response is a key target in heart failure treatment
There are two compensatory mechanisms triggered in heart failure, the sympathetic nervous system and the RAAS system. Which occurs first
The sympathetic nervous system stimulation is rapid and occurs immediately whereas the RAAS system is much slower and involves protein synthesis and multiple steps
Describe how the RAAS acts to compensate for the effects of heart failure
The juxtaglomerular apparatus in the kidney releases renin in response to the decreased cardiac output. Renin acts on angiotensinogen released by the liver, converting it to angiotensin I. Then the ACE enzymes in the lungs convert angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor acting via AT-1 receptors to increase peripheral resistance. Angiotensin II also acts to release aldosterone which promotes Na+ retention and with-it water. This acts to increases blood fluid volume
Describe how the SNS acts to compensate for the effects of heart failure
The sympathetic nervous system releases noradrenaline in an attempt to maintain arterial blood pressure and central circulation. This in order to look after the major organs such as the brain, kidney and liver. As blood pressure is controlled by peripheral resistance and cardiac output, noradrenaline acts on both peripheral resistance and cardiac output to increase blood pressure. Firstly is a powerful vasoconstrictor via the α1 adrenergic receptors in vascular smooth muscle, but it also has a positive inotropic effect by stimulation of the β adrenoceptors in the heart.
Outline the interplay that exists between the sympathetic nervous system and RAAS systems
Noradrenaline stimulates renin release in the kidney meanwhile, angiotensin II encourages the release of noradrenaline from sympathetic nerve endings. This sort of positive feedback loop acts to amplify the response
How are the effects of RAAS and sympathetic nervous system beneficial in blood loss
The sympathetic nervous system stimulation results in a tachycardia which increase cardiac output. It also has a positive inotropic effect increasing the force of contraction which also increases cardiac output. Meanwhile noradrenaline also causes vasoconstriction to increase blood pressure. Finally as a result of RAAS there is a stimulation of Na+ and water retention which acts to increase blood volume and hence blood pressure
How are the effects of the RAAS and sympathetic nervous system derogatory in heart failure
The tachycardia caused by the sympathetic nervous system also increases the workload and oxygen demand of the heart, as does the positive inotropic action also. In addition, vasoconstriction increases the afterload which therefore also increases work and oxygen demand of the heart. Meanwhile Na+ and water retention as a result of aldosterone increases preload which due to the shallow Frank-Starling relationship actually does very little to increase cardiac output. Finally, chronic adrenergic stimulation has a toxic effect on the myocytes and causes arrhythmia
What are the six different pharmacology’s that can target aspects of the sympathetic nervous system and RAAS system
Diuretics, aldosterone antagonists, ACE inhibitors, angiotensin receptor blockers, β adrenoceptor antagonists or renin inhibitors
Below is some data from the RALE trial of aldosterone antagonists in heart failure. Describe what these results show
![](https://s3.amazonaws.com/brainscape-prod/system/cm/233/547/470/q_image_thumb.png?1520077789)
Placebo – 25% 1-year mortality, Spironolactone – 17.5% 1-year mortality. Hence Aldosterone antagonists correlate with a decreased mortality in patients in heart failure. The curves are continuing to diverge indicating there is an ongoing benefit of aldosterone antagonists
Below is some data from the CONSENSUS trial of ACE inhibitors in heart failure. Describe what these results show
![](https://s3.amazonaws.com/brainscape-prod/system/cm/233/547/471/q_image_thumb.png?1520077804)
Placebo group had a 60% mortality rate over 1 year. This was an extremely severe heart failure patient cohort with NYHA type IV heart failure. However, the patient group treated with the ACE inhibitor enalapril had a 40% mortality rate. Hence the ACE inhibitor reduced the mortality rate in the patients by 1/3.
Below is some data from the AIRE trial of ACE inhibitors in heart failure. Describe what these results show
![](https://s3.amazonaws.com/brainscape-prod/system/cm/233/547/472/q_image_thumb.png?1520077815)
12-month mortality in placebo patients – just under 20%. There as a significant improvement in patients treated with Ramipril with around a 15% mortality
Below is some data from the SOLVD trial of ACE inhibitors in heart failure. Describe what these results show
![](https://s3.amazonaws.com/brainscape-prod/system/cm/233/547/473/q_image_thumb.png?1520077825)
10% rate of death or hospitalisation after 1 year in placebo patients. Improved with enalapril. Greater the annual mortality, the greater the benefit with enalapril
What are the clinical indications of ACE inhibitors
Heart failure, hypertension, diabetic nephropathy
Give some examples of ACE inhibitors
Captopril, Ramipril, enalapril
Which ACE inhibitor is most commonly used
Ramipril
ACE inhibitors are used once daily in hypertension, why are they used twice daily in heart failure
Because whereas patients with hypertension really only need the effects on blood pressure during the day, heart failure patients need its effects throughout the night when often it gets worse