Hypertension and Heart Failure-Extra Reading

Question 1

Mann, Circulation, 2005

Answer 1

-A number of experimental models have shown that high concentrations of Neurohormonal systems are sufficient to mimic some aspects of the heart failure phenotype even if heart failure isn’t present
^this indicates the neurohormonal systems AREN’T HELPING
-Clinical studies have shown that antagonising neurohormones leads to clinical improvement in heart failure patients

• Progressive activation of neurohormonal mechanisms may explain why heart failure may develop many years after an acute MI, despite the absence of ongoing ischaemia
• The most powerful compensatory mechanism activated to support the failing heart is the increase in Cardiac Adrenergic Drive i.e increases in the Sympathetic Nervous System that stimulates adrenergic receptors to increase cAMP production

The adrenergic receptor increases:

• contractile function
• heart rate
• causes myocyte hypertrophy
• volume expansion
• But long term this is maladaptive

Is the Neurohormonal Model Adequate to explain the progression of heart failure?NO
-Even though Neurohormonal therapies such as ACEi’s/ARBs and B-blockers slow heart failure, they do not stop progression all together
-This may mean that Neurohormonal mechanisms don’t cause all progression
OR
-It may be because it is not possible to inhibit all neurohormonal mechanisms because of the dose-limiting side effects of the therapeutics
-There may be alternative metabolic signalling for neurohormonal mechanisms that are not antagonised by conventional therapies
-The current portfolio of treatments may not antagonise all of the alterations in biologically active systems that become activated in the setting of heart failure
-Some neurohormonal signalling pathways that produce harmful effects in cardiac myocytes may have favourable effects elsewhere
-At some point, heart failure may progress independently of the neurohormonal status of the patient

• Natural history studies have shown that progressive LV remodelling is directly related to future deterioration in LV performance and less favourable clinical course in heart failure
• Some clinicians think that LV remodelling occurs as an end-organ response to Neurohormonal Signalling, but others think that remodelling contributes to heart failure progression independently

Question 2

Izzo, Med Clin N Am, 2004

Answer 2

• Hypertensive heart disease is SPECTRUM - represents an accumulation of functional and structural adaptations to increased BP
• Prominent features of hypertensive HF= LVH, vascular and ventricular stiffness, diastolic dysfunction

LV HYPERTROPHY

• Increased left ventricular wall thickness and mass are associated continuously with BP and age; but without increased BP, LVH doesn’t occur chronically with age
• The presence of ECG-confirmed LVH DOUBLES the risk of CV events or mortality

In the FRAMINGHAM heart study, hypertension accounted for 39% of male heart failure and 59% of female heart failure; ALOT!!

Hypertensive heart disease involves a stepwise progression from: Hypertension to LVH, then distolic dysfunction and the Ventricular dilation and HF

-The concentric hypertrophy observed in hypertensive heart disease maintains ejection fraction and cardiac output because the muscle mass is bigger and can maintain a good inotropic level. However the hypertrophy restricts diastolic filling

• The thickened ventricular wall is LESS EFFICIENT and the force of contraction per gram of muscle is reduced progressively
• As diastolic pressures rise, the contractile force cannot be maintained and the ventricular muscle begins to DILATE

-Hypertension causes higher afterload because the reflected pressure wave returns quicker which increases pressures in the ventricles

• There is CONSIDERABLE INTERINDIVIDUAL VARIATION in the response of the heart to hypertension
• Not all individuals with similar BP elevations develop LVH-TWIN AND COHORT STUDIES HAVE SHOWN THIS
• the LVH associated with hypertensive heart disease also causes:
  1. restricted coronary blood flow.
  2. increased coronary vascular resistance
  3. perivascular fibrosis
  4. arterial stiffness
  5. endothelial dysfunction and coronary atherosclerosis
• all of these make heart failure even worse!