Advanced Pathophysiology Unit 5 CV Page 1 of 24. Learning Objectives:

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1 Advanced Pathophysiology Unit 5 CV Page 1 of 24 Learning Objectives: 1) What is the definition of HF? How can we get it? Is it just the failing heart? 2) AHA/ACC stages of HF compared to older NYHA classes of functional HF 3) Recognize that LV failure can be SYSTOLIC (low output) or DIASTOLIC (high output) and know the etiologies of these types of LV failure 4) Understand the compensatory mechanisms that are initiated due to LV Systolic HF and how this results in progressive worsening of cardiac function over time 5) Recognize the contribution of longstanding HTN to HF 6) Recognize the rational approach to management of HF with current understanding of pathophysiologic mechanisms 7) Understand the etiology and compensatory changes that occur in RV HF.

2 Advanced Pathophysiology Unit 5 CV Page 2 of 24 METs AS AN ESTIMATE OF FUNCTIONAL CAPACITY/PROGNOSIS: Part of preop evaluation and prognostic determination Don t mix this up with MetSyn (Metabolic Syndrome a cardiometabolic disorder) Exercise Capacity and METs: We are measuring exercise capacity reported in metabolic equivalents of task (METs) These are units based on the metabolic resting oxygen uptake while sitting. o 1 MET = oxygen consumed at rest = 3.5 ml of oxygen/kg/min. Examples of METs: o I am always surprised to see that a METs of 6 is bedmaking! It always seems like hard work to me! o Carrying a suitcase is a METs of 7. METs testing results and prognosis: o Exercise capacity of 5 METs or less expect poor prognosis in patients <65 yo o Exercise capacity of 10 METs expect prognosis with medical therapy same as CABG o Exercise capacity of 13 METs is a good prognosis even if the exercise testing reveals abnormal EKG or BP responses Predictive value of METs: Expected values for age have been established and deviations are predictive of coronary survival rates Gulati M, et al. The prognostic vlaue of a nomogram for exercise capacity in women. N Eng J Med 4 Aug 2005; 353(5):

3 Advanced Pathophysiology Unit 5 CV Page 3 of 24 WHAT IS THE DEFINITION OF HEART FAILURE (HF)?? inability of the heart to supply enough blood carrying oxygen & nutrients for the needs of the body's tissues. also called congestive heart failure (CHF) when there is fluid accumulation that is clinically significant however, this is really an OLDER term, and the current abbreviation is really just HF You do not have to have congestion in order to have HF your goal is to diagnose HF long before congestive symptoms (by the time the patient is symptomatic, we have missed the diagnosis by years and years) Many ways to get HF may NOT be the fault of the HEART!!! body needs more O2 (hypermetabolic state) heart is actually fine insufficient RBC to carry O2 (anemias) heart is actually fine failure of myocardium (pump) to provide sufficient SV per heartbeat (insufficient CO) due to poor preload return (e.g. dehydration) heart is actually fine Thus, metabolic needs, hematologic and volume factors play a role, not just cardiac issues.

4 Advanced Pathophysiology Unit 5 CV Page 4 of 24 HF ETIOLOGY: (see also pictures next pages) Cardiac: clinicians usually refer to Left Ventricular dysfunction when they talk about HR disease states that reduce ventricular contractility OR reduce compliance ( stiff ventricle ) Examples: o valvular heart disease (increases myocardial work load) o coronary artery disease (reduces oxygen supply to the heart) o intrinsic myocardial diseases (cardiomyopathies hypertension, alcoholism, etc.) Howeve, it is now recognized that right ventricular dysfunction is also found in MANY HF patients Non-cardiac causes of HF: systemic diseases (anemia with reduced viscosity) high CO states such as in thyrotoxicosis, pregnancy, AV fistula LOW-output heart failure (from Left Ventricular Systolic Dysfunction): the heart is pumping LESS blood/minute, due to systolic HF, reduced CO LOW output HF is usually what is referred to when we use the term HF clinically Due to underperfusion of the kidney, the RAS is activated and eventually volume overload occurs HIGH-output heart failure from Left Ventricular Diastolic Dysfunction: the LV is functioning well and the heart may be pumping LOTS of blood BUT the tissues are still not receiving sufficient supply. Causes: o when the heart receives too much venous return (decreased TPR) o greatly increased blood volume overloading the heart and causing increased atrial pressures with fluid backup (like in thyrotoxicosis, pregnancy). Diastolic dysfunction is a form of high output failure o can lead to pulmonary venous congestion, even with normal systolic ventricular function. o Found in disease of ventricular filling Anything making the ventricle STIFF (reduced LV compliance) Includes ventricular scarring, hypertrophy, ischemic cardiomyopathy, hypertensive cardiomyopathy, amyloidosis, sarcoidosis Hypertrophic Normal Dilated Different cardiac remodeling changes (cardiomyopathy) the LV may be hypertrophic (increased muscle mass) or dilated; either change interferes with normal filling (diastole) and contraction (systole).

5 Advanced Pathophysiology Unit 5 CV Page 5 of 24 Typically we are referring to cardiac problems (not systemic) when we talk about HF: Usually there is dysfuncton of the left ventricle This can be systolic or diastolic Usually secondary to longstanding Hypertension, RAS activation Comorbidities include cardiac ischemia Complications include ischemic cardiomyopathy & dysrhythmias (arrhythmias)

6 Advanced Pathophysiology Unit 5 CV Page 6 of 24 TALKING ABOUT LEFT VENTRICULAR HF:

7 Advanced Pathophysiology Unit 5 CV Page 7 of 24 Left ventricular disease causing HF may be Systolic or Diastolic: Systolic is LV pump failure associated with volume overload and eventual edema, pulmonary congestion (the typical picture of HF as envisioned by most clinicians) o Also referred to as low output Diastolic is LV stiffness poor compliance, poor filling actually has normal ejection fraction and there isn t any volume overload o Also referred to as high output Patients can have either type, or a combination of both Typically, when people talk about HF due to LV dysfunction, they are thinking about LV pump failure and systolid dysfunction However, it is becoming increasingly obvious that diastolic dysfunction of the LV is important in the etiology of HF as well THIS CHART ILLUSTRATES FINDINGS IN LEFT VENTRICULAR HF: May be SYSTOLIC OR DIASTOLIC OR A COMBINATION OF BOTH

8 Advanced Pathophysiology Unit 5 CV Page 8 of 24 AHA/ACC HF STAGES COMPARED TO OLDER NYHA FUNCTIONAL CLASSES : NO LONGER WAIT FOR SYMPTOMS OR FUNCTIONAL DISABIILTY TO MAKE THE DIAGNOSIS The diagnosis is made on risk factors and evidence of structural heart disease (e.g. on CXR, EKG, echocardiogram, other diagnostic studies) Symptomatic disease is the result of failure to diagnose early and treat early Early intervention is now the practice guideline Recommendations are for guideline-directed medical therapy (GDMT) AHA/ACC 2013 CPG for Heart Failure Executive Summary: Full CPG: Determination of Ejection Fraction: Is it preserved? Is it reduced? Current terminology: o HF with preserved EF is termed: HFpEF (EF 50% or more)( diastolic HF) o HF with reduced EF is termed: HFrEF (EF 40% or less)( systolic HF)

9 Advanced Pathophysiology Unit 5 CV Page 9 of 24 Stages of HF:

10 Advanced Pathophysiology Unit 5 CV Page 10 of 24 FIRST LET S TALK ABOUT LEFT VENTRICULAR SYSTOLIC HF: low output HF LV Systolic HF: Defects in the SYSTOLIC contractile state cause a reduced ejection fraction This decreased circulation of blood will result in reduced venous return to the heart. OVERALL there is reduced CO This creates compensatory changes in the RAS that result in fluid overload. (see more next pages) FROM: McMurray JJV. Systolic Heart Failure. NEJM 21 January 2010;362(3): (with permission)

11 Advanced Pathophysiology Unit 5 CV Page 11 of 24 LV Systolic HF: Pump Failure (LV failure) Backward Effects Forward Effects Cardiac Poor ejection fraction LV reduced compliance Reduced cardiac output Increased LVEDP Increased LA pressure Increased Pulmonary artery pressure Pulmonary Symptoms cough, dyspnea, DOE PND, orthopnea, Pulmonary Signs cyanosis auscultatory crackles & rales Reduced GFR & poor renal perfusion Activate RAS fluid retention LVH accelerated atherosclerosis worsened pump function (preload & afterload) Reduce CO & BP Adaptive changes Increased HR increased MVO2 cardiac ischemia Peripheral edema (pitting from extravasated protein due to high pressures) see below for discussion

12 Advanced Pathophysiology Unit 5 CV Page 12 of 24 Symptoms & signs: cyanosis fatigue dyspnea (sense of oxygen debt & breathlessness) due to both poor tissue circulation as well as poor oxygenation at the lung from pulmonary congestion. What worsens HF decompensation: o Anything placing a greater workload on the heart (exercise, stress, illness, surgery) o Anything lessening pump effectiveness (atrial fibrillation and loss of atrial kick) will worsen the HF. Cardiac changes: due to compensatory mechanisms designed to increase the venous return (preload, or LVEDP). This increases the SV according to the Frank-Starling curve o increased filling leads to increased ventricular stretch o increased LVEDP in turn causes increased contractility. However, this improved contractility only lasts up to a point o once the LVEDP becomes too high, cardiac function declines o now you are left with a large, STIFF ventricle that is POORLY COMPLIANT. Even diastolic filling becomes difficult! Can t relax enough to fill. Plus, disease causes increased energy requirements even for diastolic relaxation (remember relaxation is an active process). Pulmonary edema: HP > COP in pulmonary capillaries Back pressure into the lungs develops (since the left atrium and left ventricle are not accepting and ejecting blood properly), with pulmonary vascular congestion. This means that there is an increase in the pulmonary capillary pressures (PCP), exceeding the COP net fluid filtration from vascular space to pulmonary interstitium. Once fluid enters the interstitium, this is pulmonary edema, a medical emergency. Hypercapnia & hypoxia will be seen when this stage is reached. The kidney talks to the heart, the heart talks to the kidney to worsen left systolic HF: Increasing blood volume (renin-angiotensin-aldosterone): o Due to poor renal perfusion in HF, the RAS system is activated, increasing blood volume. o This is initially helpful but leads to overshoot and worsened pump action with development of pulmonary edema. Thus, systolic heart failure is usually associated with INCREASED BLOOD VOLUMES

13 Advanced Pathophysiology Unit 5 CV Page 13 of 24 Compensatory ( adaptive ) physiologic measures of the failing left heart: Compensatory hypertrophy (LVH) & dilatation: o allows a greater filling and increased LVEDP o with greater force of contractility (increased SV & EF). o But, eventually, dilatation & hypertrophy become disease in itself, with a stiff noncompliant ventricle that exceeds the benefits of the Frank-Starling curve and we now have diastolic heart failure (see below) Exacerbation of myocardial ischemia: o the LVH may exacerbate coronary ischemia o since coronary artery blood flow may not be sufficient to supply the thickened myocardium with the necessary coronary muscle blood supply o Plus, the stiff ventricle has a high MVO2 requirement and worsens angina Remodeling as a long term complication of infarct: o when infarct & loss of muscle tissue is the cause of the failing heart o the term VENTRICULAR REMODELING indicates that compensatory ventricular dilatation & hypertrophy has taken place in response to the infarct o Improved cardiac output (temporarily) but at the expense of a stiff (noncompliant) LV that develops diastolic heart failure (see below) Reduced Renal Perfusion Activates the RAS to raise the CO: o angiotensin-ii, ADH, Aldosterone o fluid and salt loading, blood volume expansion preload o increased sympathetic nervous system activity afterload & increased inotropy And remember the additional changes in the body include compensatory increase in the TPR: Sympathetic stimulation: o sympathetic stimulation causes peripheral vasoconstriction to enhance preload. o But, this also raises the MVO2 and worsens the condition. o Eventual long term result is worsened heart failure RAS activation: o Increasing blood volume (renin-angiotensin-aldosterone): Due to poor renal perfusion in HF, the RAS system is activated, increasing blood volume. This is initially helpful but leads to overshoot and worsened pump action with development of pulmonary edema. o Thus, systolic heart failure is usually associated with INCREASED BLOOD VOLUMES

14 Advanced Pathophysiology Unit 5 CV Page 14 of 24 A continuum of worsened pathology: Anatomical changes in the heart over time based on comorbid factors: You may hear of eccentric vs. concentric changes in the anatomy of the heart The actual remodeling of the left ventricle may differ, based on the factors leading to HF

15 Advanced Pathophysiology Unit 5 CV Page 15 of 24 Eventually what happens? Loss of Ejection Fraction and cardiac decompensation : Is it preserved? Is it reduced? Current terminology: o HF with preserved EF is termed: HFpEF (EF 50% or more)( diastolic HF) o HF with reduced EF is termed: HFrEF (EF 40% or less)( systolic HF) Classification of acutely decompensated HF LOSS of ejection fraction:

16 Advanced Pathophysiology Unit 5 CV Page 16 of 24 Clinical result: Ventricular Remodeling compensatory hypertrophy (LVH) & dilatation striving to maintain ejection fraction after infarct: o when infarct & loss of muscle tissue is the cause of the failing heart o the term VENTRICULAR REMODELING indicates that compensatory ventricular dilatation & hypertrophy has taken place in response to the infarct o Improved cardiac output (temporarily) o allows a greater filling and increased LVEDP with greater force of contractility (increased SV & EF) to improve the CO for the body o But, eventually, dilatation & hypertrophy become disease in itself, with a stiff noncompliant ventricle that exceeds the benefits of the Frank-Starling curve. Exacerbation of myocardial ischemia: LVH may exacerbate coronary ischemia since coronary artery blood flow may NOT be sufficient to supply the thickened myocardium with the necessary coronary muscle blood supply Plus, the stiff ventricle will have a higher MVO2 requirement and also worsens angina Reduced Renal Perfusion Activates the RAS to raise the CO: o angiotensin-ii, ADH, Aldosterone are released o fluid and salt loading occurs with blood volume expansion preload o increased sympathetic nervous system activity increased afterload & increased inotropy Final result: o inotropic stress & chronotropic stress, with increased MVO2 requirement o poor perfusion and renal activation of the RAS with increased volume/salt loading o worsened angina (chest pain), cardiac decompensation (pulmonary & peripheral edema) o reduced ejection fraction (EF < 50%) Pharmacologic correlate rationale for drug therapy: ACE-inhibitors (ACEI) and ARBs (angiotensin receptor blockers) are now utilized in the management of HF; the long-term use of these agents can actually REVERSE remodeling & compensatory LVH. diuretics are also used to relieve congestion from fluid overload caused by activation of the RAS Beta-blockers are used to blockade the Beta-1 receptor on the heart and reduce inotropy & chronotropy, both reducing the MVO2 required for cardiac function. Aldosterone antagonists prevent the Na/H20 retention from this hormone. Severe decompensated HF is treated with IV Natrecor, which is actually exactly the same atrial natriuretic peptide (ANP) hormone the atria make in fluid overload.

17 Advanced Pathophysiology Unit 5 CV Page 17 of 24 SUMMARY of LV SYSTOLIC HF: In HF, the compensatory mechanisms are designed to increase the CO to meet the demands of the tissues Mechanisms: o Sympathetic discharge increased heart rate, increased inotropy, RAS activation o RAS activation (from hypoperfusion) volume loading, vasoconstriction, cardiac remodeling Overall effects of compensatory mechanisms: o Increased EF (ejection fraction) initially due to the compensation o Increased afterload via peripheral vasoconstriction (sympathetic, RAS) o Increased vascular compartment volume from systemic activation and reserve volume (stored in legs and spleen) restored to blood vessels o This also improves preload return to the heart o Increased preload stretches heart and results in better force of contraction (inotropy) o At the same time, local tissue factors may promote vasodilatation to meet the tissue s need for oxygen better perfusion of the tissues also results in increased preload return to the heart o Increased heart rate (HR) How these compensatory changes help the body INITIALLY: o INITIALLY improved preload, improved vascular volume, positive inotropy, positive chronotropy all raise the CO at first How this all EVENTUALLY hurts the heart and makes everything WORSE: o Overall, longstanding compensatory changes of increased inotropy, increased chronotropy, increased preload (volume loading), increased LV muscle mass (LVH) create myocardial ischemia, myocardial cell damage (cardiomyopathy) and worsening LV function. o Increased chronotropy (HR) diastolic phase is shortened (more than the systolic phase) this is when the coronary vessels receive their blood; the coronary circulation is reduced & less blood is delivered to the myocardium o Increased inotropy & chronotropy more cardiac muscle demand for oxygen, at just the time when the coronary vessels are delivering less blood!! o LVH makes the muscle thicker and it is harder to deliver blood to this thick muscle mass; LVH also makes the ventricle stiff and it can t fill during diastole o Acute decompensation will occur with symptomatic HF (edema, pulmonary congestion) ejection fraction is NO LONGER PRESERVED o All of these compensatory changes from the sympathetic NS & the RAS raise the MVO2 just at a time when the blood delivery is being reduced! So, in heart failure the tissues need more oxygen it is tempting to increase the CO to meet the demands of the tissues but you need to worry about the MvO2!! Read the above paragraph a few times so you ve got it this is the current view of HF pathophysiology. This is why the current treatment is to BLOCK the RAS (ACEI & ARB drugs), BLOCK the sympathetic NS (beta-blockers); and NOT to use cardiotonics like digoxin. Diuretics are still used to treat edema/congestion on a PRN basis for patient relief if congestion symptoms occur in later stages of HF, but these drugs do not alter the actual pathology of HF.

18 Advanced Pathophysiology Unit 5 CV Page 18 of 24 NOW LET S TALK ABOUT ANOTHER LV PATHOLOGY: WHAT IS DIASTOLIC LEFT VENTRICULAR FAILURE? high output HF This is still left ventricular pathology: Results from any condition that causes REDUCED COMPLIANCE of the LV Thus, the LV is stiffer Think: o post-mi scarring o left ventricular hypertrophy (thickened myocardium) o other cardiomyopathies and other conditions (e.g., amyloidosis, sarcoidosis) Typically: o The myocytes are not efficient in extracting and using oxygen o There is often evidence of myocyte disease or dysfunction ( sick myocytes ) Differences in pathophysiology: Does NOT activate the renin-angiotensin system Blood volumes are NOT elevated EF (ejection fraction) is maintained (>50%) Difference in clinical presentation: May be very difficult to recognize that there is diastolic heart failure in early stages May only be recognized towards the end of the natural history of the development of the condition

19 Advanced Pathophysiology Unit 5 CV Page 19 of 24 Graphic of the differences between LV systolic & LV diastolic dysfunction:

20 Advanced Pathophysiology Unit 5 CV Page 20 of 24 LASTLY WHAT IS COMBINED DIASTOLIC & SYSTOLIC LEFT VENTRICULAR HF? When both systolic AND diastolic failure is present, the clinical presentation may be very complex and not as physiologically simple More common than previously thought

21 Advanced Pathophysiology Unit 5 CV Page 21 of 24 MOVING ON LEAVING THE LEFT VENTRICLE WHAT ABOUT RIGHT VENTRICULAR SYSTOLIC HEART FAILURE? There can be a failure of the myocardium in the right ventricle as well Findings are different clinically than in left ventricular systolic failure Note that the systolic phase we are referring to here is for the RIGHT ventricle Usually due to pulmonary disease and called cor pulmnale (see more below) May also be due to longstanding LV systolic failure (see more next page) Right Ventricular Failure Backward Effects Forward Effects Decreased Ejection Fraction Decreased output to left ventricle Increased right ventricle preload Decreased left ventricular cardiac output Increased right atrial pressure Systemic Congestion hepatosplenomegaly anorexia peripheral edema jugular vein distension Findings reduced GFR oliguria fatigue decreased mentation narrow pulse pressure faint pulses increased HR See discussion below

22 Advanced Pathophysiology Unit 5 CV Page 22 of 24 Primary RV failure: acute, usually RV infarct if the RV fails, as much as 50% of pulmonary blood is shifted into the systemic circulation (5% of total body blood volume) results in a lack of venous return to the heart. Treatment of acute RV failure: Sounds strange it is rapid continuous fluid infusion to maintain return of blood to the left heart and presersve systemic CO Etiology: RV infarct. RV failure due to pulmonary conditions Cor pulmonale: enlarged RV due to any cause OTHER than LV failure. This might be due to primary lung disease & chronic pulmonary artery afterload pressures. A clue that this is the case: o hypercapnia & hypoxemia are severe early in the disease (pulmonary component) o unlike in LV failure, ABG abnormalities only occur during the last stages with terminal pulmonary edema Etiologies: usually lung pathologies such as primary/idiopathic pulmonary hypertension, pulmonary emboli, & COPD. RV failure due to LV failure (HF): LV failure increases PCP in the pulmonary vascular compartment (see LV heart failure, above). If this congestion becomes very high, pulmonary artery hypertension (pulmonary hypertension) occurs, giving an afterload increase to the RV & overloading the RV. Cardiac etiologies: o NOT called cor pulmonale o is a high output cardiac failure, with usually large volumes of blood o such as in tricuspid regurgitation, Atrial Septal Defect (ASD) where blood to travels from the left right heart with RV overload).

23 Advanced Pathophysiology Unit 5 CV Page 23 of 24 EKG FINDINGS OF CARDIAC HYPERTROPHY: ATRIAL HYPERTROPHY right and left: Right atrial hypertrophy (enlargement) (RAE): Same as above, except there is a tall initial component Left Atrial hypertrophy (enlargement)(lae): Large P wave Diphasic P wave with wide terminal component (look in lead II) Usually indicates pulmonary disease (e.g. COPD) VENTRICULAR HYPERTROPHY right and left: Right ventricular hypertrophy (RVH): R > S in V1 (tall R in V1 & V2), R gets smaller from V1 V6 S wave persists in V5 & V6 RAD with widened QRS May also RAE Confirm diagnosis with echocardiogram o Color Flow Doppler gives more information blood flow, valves, wall motion, ejection fraction, etc. (but is more expensive) This tracing has RVH & RAE

24 Advanced Pathophysiology Unit 5 CV Page 24 of 24 Left ventricular hypertrophy (LVH): S wave V1 + R wave V5 > 35 mm COUNT THE BOXES FOR MM ELEVATION o This is called voltage criteria for LVH o There are other ways (probably more accurate) to diagnose LVH on EKG LAD with widened QRS Inverted T wave with gradual downward slant and then rapid upstroke o LVH with strain o When the strain pattern is seen, the diagnosis of LVH is more accurate o Usually the result of longstanding HTN or valvular obstruction o Note that LVH with strain identifies hypertensive patients at risk of developing HF and also dying of HF (even with aggressive BP management) (the LIFE study) How to confirm LVH diagnosis: o If EKG signs of LVH, always order an echocardiogram to confirm o The Color Flow Doppler Echo will give more information about the blood flow, ejection fraction, and wall motion but it is more expensive Sometimes, a limited Echo is done to simply look for o Ventricular hypertrophy or Septal hypertrophy o These are the gold standard of LVH diagnosis o If confirmed, a Color Flow Doppler can be ordered How to decide which ECHO to order?? o The Athlete: The normal athlete may have EKG signs of LVH But, the physical exam is normal and no evidence of cardiovascular disease so this would be a good candidate for the limited Echo o The hypertensive patient: Any signs of LVH here are probably due to cardiac changes from HTN Go ahead with the Color Flow Doppler