Diastolic HF Flashcards
Heart Failure with Preserved Ejection Fraction (HFpEF) definitions
(diastolic HF) Clinical definition: o Clinical syndrome of HF o Normal LV ejection fraction (> 50%) o No other etiology of the symptoms Pathophysiological definition: o Filling of the LV to a normal end diastolic volume only occurs at higher than normal pressures Diagnosis: o Meet clinical definition of HF o Ejection fraction normal or nearly normal (>50%) o Assess diastolic function (Echo)
Explain the four phases of diastole, with emphasis on when valves open and close and when filling is occurring.
Iosvolumetric relaxation
o Valves closed
o Myocardial relaxation → LV pressure falls
o When LV < LA pressure → mitral valve opens
Rapid ventricular filing
o Active relaxation of LV
o ATP required for Ca2+ sequestration in SR and myosin dissociation from actin
Diastasis
o LV filling rate determined by diastolic passive ventricular stiffness (rate of pressure rise with increasing ventricular volume)
Atrial systole
Describe how abnormalities of both relaxation and ventricular compliance lead to diastolic dysfunction.
Impaired ventricle relaxation
o Slow relaxation → slowed decrease in pressure during early diastole = early diastolic filling only under higher pressure
o More dependent on atrial kick (bigger problem if go into atrial fibrillation)
Increased ventricle stiffness
o Diastolic pressure rises at abnormally fast rate → elevated end diastolic pressure
o Rapid phase filling that ends quickly (tolerates Atrial fibrillation better)
Importance of HR
o Increase HR → shortened diastolic length = incomplete LA emptying → increased LA and pulmonary pressures; decreased SV
Impaired exercise response
o Failure of Frank-Starling relationship
o Normally: heart able to increase LV end diastolic volume with increased pulmonary capillary wedge pressure
o In HFpEF: can increase volume with exercise → exercise intolerance
Identify the major chronic illnesses and other conditions prevalent in the United States that predispose to diastolic dysfunction.
- Diabetes mellitus
- Hypertension
- Hypertrophic cardiomyopathy
- Aging
- Obesity
- Female gender
Requirements for normal relaxation and filing
o Ca2+ removal from cytosol
o Myosin dissociation from actin
o Ventricular compliance is high
o Ventricular afterload is normal
Pathophysiologic mechanisms of diastolic dysfunction: Altered Ca2+ handling
- Hypertrophic hearts in patients with HT have prolonged Ca2+ transients
- May lead to diastolic tension
- Post MI: abnormal Ca2+ handling
- SERCA downregulation → increased diastolic Ca2+
Pathophysiologic mechanisms of diastolic dysfunction: Increased myofilament Ca2+ sensitivity
- In animal models for systolic HF
- Lead to diastolic abnormalities
- Leads to persistent diastolic tension development
- Problem: lack of animal models for HFpEF
Pathophysiologic mechanisms of diastolic dysfunction: Altered myocardial metabolism
- Diastole depends on supply of ATP
- Energy depletion → diastolic tension development
- May be important in diabetes = energy usage is deranged
Pathophysiologic mechanisms of diastolic dysfunction: Changes in ECM
- Increased ventricular stiffness from increased collagen deposition, interstitial fibrosis
- Result: decreased ventricular compliance
- Left shift in diastolic pressure-volume relationship
- Late diastolic pressure elevation
Pathophysiologic mechanisms of diastolic dysfunction: RAAS activation
- Hypertrophied hearts = have increased ACE in myocardium
- Leads to locally increased levels of Angiotensin II
- Angiotensin II and aldosterone are pro-fibrotic in heart and blood vessels → increase stiffness
- BUT trials of angiotensin receptor blockers have not had significant effects
Pathophysiologic mechanisms of diastolic dysfunction: Increase systolic ventricular stiffness
- Diastolic function influenced by preceding systole
- Abnormal compliance in systole → decreases amount of recruitable contractility available (contractile reserve)
- Result: changes response to increases in preload, afterload and physiological stress
Pathophysiologic mechanisms of diastolic dysfunction: Increased arterial stiffness
- Alters pressure wave travel in aorta
- Reflected wave back to aorta from iliac bifurcation
- Normal/ young: reflected wave returns in early diastole
- Augments diastolic pressure
- Improves coronary blood flow
- Stiff arteries (aged): reflected wave returns earlier
- Late systolic loading of the heart → increased preload
- Ventricular hypertrophy
- Prone to ischemia due to high demand and low supply
Arterial stiffening in: • Increased age • Contributes to isolated systolic HR seen in elderly • Hypertension • Diabetes • Cigarette smoking • Hypercholesterolemia • Sedentary lifestyle • Abdominal obesity
Identify common precipitants of clinical diastolic heart failure.
Exercise
Hypertension
o High afterload → impaired ejection → end systolic volume rises slightly
o Result: abnormally large diastolic volume → increased pressure
Atrial arrhythmias (ex. Atrial fibrillation)
o With abnormal diastolic fuction, increased dependence on atrial kick
o Without atrial contraction → worsened symptoms
o With tachycardias: shortens diastole
Myocardial ischemia
o Impaired ventricular relaxation since needs lots ATP
Tachycardia
o Ex. Acute illnesses like pneumonia; or pain
o From shortening of diastolic filling period
Discuss treatment strategies of diastolic heart failure.
Treat underlying chronic diseases
o HT, diabetes
o Maintain sinus rhythm to decrease symptoms (allow benefits from atrial kick)
o Treat ischemia to decrease symptoms
• Ischemia induces increased ventricular stiffness and abnormal relaxation
o Prolong diastole → more diastolic filling time
o Exercise program to improve diastolic function
• Increases vagal tone → slower HR
Understand filling = use therapy appropriately
o Echo = pattern and rate of flow from LA to LV
Few proven drug therapies:
o Angiotensin receptor blocking drugs
o Aldosterone antagonist (ongoing trial)
Describe the changes in aortic pressure contour seen with arterial stiffening and the mechanisms by which this may impair diastolic function.
Flow from LA to LV during diastole is imaged by Doppler ultrasound:
Normal:
o E wave: early filling as mitral valve opens
o Period of diastasis
o A wave: late filling from atrial systole
Slowed ventricular relaxation rate:
o E wave shape changes
o Blood can’t enter ventricle as quickly
o Atrial contraction becomes more important
o Result: atrial arrhythmias poorly tolerated
Stiffened ventricle
o E wave tall and peaked
o Ventricular pressure rises quickly in diastole → Nearly all filling in early diastole
