Heart Failure Part 1 Flashcards
Epidemiology of Heart Failure
- ~2-2.5 % of Americans with HF or ~ 6.7 million people: Age related increase: 5% (60-69); 7% (70-79); 10% (80+)
- Lifetime risk is ~24%
- ~ 1 million new cases are diagnosed and approximately
284,000 people die from HF each year - Increase in the number of hospital admissions for HF, ~1 million patients annually.
- HF is the most common hospital discharge for patients >65 years of age.
- Management in 2012 cost an estimated $ 39 billion, with ~1/10 associated with drug costs!
- Prognosis: Survival rates: 5 years: ~50 %
Definitions of Heart Failure
- Although heart failure can be readily described as a clinical syndrome……..an abnormality of myocardial function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues
- Not a single disease state but the final common pathway for CV diseases: CAD, HTN, valvular Dz, cardiomyopathies (intrinsic diseases of the heart)
Pathogenesis of Heart Failure
CAD, HTN, cardiomyopathy, valvular disease –> left ventricular dysfunction –> remodeling –> decrease EF –> death (from arrhythmia + pump failure)
non-cardiac factors: endothelial dysfunction, neurohormonal activation, vasoconstriction, Na retention –> symptoms –> chronic heart failure
Types of HF
HFreEF - HF with reduced ejection fraction, HF sx with EF < 40% (w/o sxs… asymptomatic reduced EF)
HFpEF - HF with preserved ejection fraction, HF sx with EF > 50%
Impairment in cardiac function
HFrEF: Systolic Dysfunction - Decreased contractility; HFpEF: Diastolic dysfunction - Impairment in ventricular relaxation/filling
Causes of HF
HFrEF: Dilated Ventricle -
* Ischemic Dilated CM (~70% of cases)
* Non-Ischemic Dilated CM
* (HTN, Thyroid Dz, Obesity, Stress, Cardiotoxins, Myocarditis, Idiopathic, Tachycardic, Peripartum)
HFePF: Recognized as the 1o disturbance in many patients with HF. Many patients have a combination of systolic and diastolic dysfunction.
HTN is most common cause (>60%)
Determinants of Left-Ventricular Performance (meaure using Stroke Volume)
- Preload: Venous return; LV end-diastolic volume
- Myocardial contractility: Force generated at any given LVEDV
- Afterload: Aortic impedance and wall stress
Cardiac and Heart Failure Hemodynamics
heart failure: can’t fill it anymore w/o it causing pulmonary congestion; preload increase –> stroke volume increase
Heart Failure Pathophysiology
cardiac output decreases –> decrease in BP and organ perfusion –> activates and causes increase in SNS, RAAS, vasopressin, ANP/BNP –> CM hypertrophy, cell death, fibrosis, arrhythmias
Compensatory Response
increased preload due to Na/water retention
vasoconstriction
tachycardia and increased contractility (SNS activation)
ventricular hypertrophy and remodeling
beneficial and detrimental effects of compensation - increased preload due to Na/water retention
beneficial: Optimize stroke volume via Frank-Starling mechanism
detrimental:
* Pulmonary/systemic congestion and edema
* Increased MVO2
Beneficial and detrimental effects of compensation - vasoconstriction
beneficial:
* Maintain BP in face of reduced CO
* Shunt blood from nonessential tissues to the heart
detrimental:
* Increased MVO2
* Increased afterload
decreases SV and further activates the compensatory responses
Beneficial and detrimental effects of compensation - tachycardia and increased contractility (SNS activation)
beneficial: maintain CO
detrimental:
* Increased MVO2
* Shortened diastolic filling time
* b-receptor downregulation and decreased responsiveness
* Ventricular arrhythmias
* Increased risk of myocardial cell death
Beneficial and detrimental effects of compensation - ventricular hypertrophy and remodeling
beneficial:
* Maintain CO
* Reduce myocardial wall stress
Decreases MVO2
detrimental:
* Diastolic and systolic dysfunction
* Risk of myocardial cell death and ischemia
* Risk of arrhythmias
* Fibrosis
Drug-Induced Heart Failure
Antiarrhythmics: (disopyramide, flecainide)
β-blockers: (atenolol, propranolol, metoprolol)
Calcium channel blockers: (verapamil, diltiazem)
Itraconazole
NSAIDs and COX-2 inhibitors
Clinical Presentation of HF
SOB, swelling of feet and legs, chronic lack of energy, difficulty sleeping at night due to breathing problems, swollen or tender abdomen with loss of appetite, cough with frothy sputum, increased urination at night, confusion and or impaired memory
Major Signs/Symptoms of Pulmonary Congestion
- Exertional dyspnea (DOE)
- Orthopnea
- Paroxysmal nocturnal dyspnea (PND)
- Rales
- Pulmonary edema
- Bendopnea
Major Signs/Symptoms of Systemic Venous Congestion
- Peripheral edema
- Jugular venous distension (JVD)
- Hepatojugular reflux (HJR)
- Hepatomegaly, ascites
Other Major Non-specific Findings
- Fatigue, weakness and exercise intolerance
- Nocturia
- Cardiomegaly
Laboratory/Clinical Assessment of HF
- Clinical assessment: H/P, medication history, S/S’s above, Cardiac risk factors
- Initial laboratory assessment: CBC, serum electrolytes, BUN, Cr, TFTs; Electrocardiogram; Chest X-ray
- Natriuretic peptides: BNP (>35 pg/mL); NT-proBNP (>125 pg/mL) - can rule out other non-cardiac causes of dyspnea if come in with elevated levels
Evaluation of LV function and measurement of EF
Echocardiogram; Nuclear testing (Single- photon emission computed tomography, MUGA - gold standard); Cardiac catheterization; MRI and CT
Classification of Patients with HF NYHA FC
I: Patients with cardiac disease but without resulting limitations of physical activity.
II: Patients with cardiac disease resulting in slight limitations of physical activity.
III: Patients with cardiac disease resulting in limitations of physical activity.
IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.
Classification of Patients with Chronic HF AHA Staging
A: High risk of developing HF. No identified structural or functional abnormalities of the pericardium, myocardium, or cardiac valves and have never shown signs or symptoms of HF.
B: Structural heart disease that is strongly associated with HF but NO signs or symptoms of HF
C: Current or prior symptoms of HF associated with underlying structural heart disease.
D: Advanced structural heart disease and marked symptoms of HF at rest despite maximal medical therapy and who require specialized interventions.
Classification Summary
NYHA 1: no sx
NYHA 2: sx with moderate exertion
NYHA 3: sx with minimal exertion
NYHA 4: sx at rest
A: no structural heart disease, no sx of HF
B: structural heart disease, no HF sx
C: structural heart disease with prior or current sx
D: refractory HF sx requiring specialied interventions (marked sx at rest)
Asymptomatic rEF
AKA: Asymptomatic LV systolic dysfunction; No Heart Failure symptoms with EF < 40%
HFrEF
Heart Failure symptoms with EF < 40%
HFimpEF
Previous Sxs/rEF now improved
HFmrEF
Heart Failure symptoms with EF 41-49%
Therapy of Asymptomatic rEF and HFrEF
- Goals of Therapy: The relative importance of each is dependent on the patient’s stage/class
1. Slow disease progression
2. Reduce Sxs and improve QOL and prevent/reduce hospitalizations and need for emergency care.
3. Reduce mortality
Therapy Based on Stage
- High Risk for HF: Stage A
- Asymptomatic rEF: Stage B; NYHA FC I; Reduced LV Ejection Fraction with No Symptoms
- HFrEF: Stage C, D; NYHA FC II-IV; Reduced LV Ejection Fraction with Symptoms
General Measures
- Treat underlying cause(s) [e.g. HTN, CAD, DM]
- Remove precipitating causes (e.g. excessive fluid,
inappropriate drug Tx) - Exercise: Caution during acute Sxs; Regular exercise (walking and cycling) should be encouraged in all patients with stable HF. The need for cardiac rehabilitation should be assessed in each patient; Dynamic exercise (walking, biking, etc.) to increase HR to 60-80 % of maximum for 20-60 minutes 3-5 times/week.
Dietary Measures
- Sodium: Intake should be restricted to 2- 3 grams/day as possible (3 gram maybe more
palatable); Avoid salty foods and salt at the table; Patients with severe HF may require diets with < 2 grams/day. - Alcohol: Patients with EtOH induced HF; abstain totally from EtOH; In others, no more than 2 drinks/day (♂) and 1 drink per day (♀)
- Fluid intake: Restriction to < 2 L/day in patients with hyponatremia (< 130 mEq/L) or if Tx with diuretics is difficult in maintaining fluid volume
General Measures cont.
- Weight monitoring (and reduction as necessary)
- General education of patients and families: Non-drug and drug therapies; Sxs of worsening HF (weight and Sx changes) and prognosis; THIS SHOULD BE A MAJOR ROLE FOR PHARMACISTS IN ALL SETTINGS.
- Smoking cessation
- Immunizations (Influenza, Pneumococcal, COVID-19)
- Mx and replace electrolytes (esp. K and Mg)
- Appropriate thyroid disease management
- Herbal products and Nutritional Supplements? Hawthorne, Coenzyme Q, etc.
Drug Therapy: Potential Pharmacologic Strategies
- Reduce intravascular volume (diuretics - don’t improve survival, SGLT2i - decrease mortality)
- Increase myocardial contractility (positive inotropes)
- Decrease ventricular afterload (ACEIs, vasodilators, SGLT2i)
- Neurohormonal blockade: ARNIs, β-blockers, ACEIs, ARBs, MRAs, SGLT2i
GDMT for Stage A
Drug therapies for routine use if atherosclerotic vascular disease is present: ACEI/ARB
GDMT for Stage B
Drug therapies for routine use if previous MI or asymptomatic rEF: ACEI/ARB (Class I Evidence A); Beta-blocker (Class I Evidence A)
GDMT Stage C/D
HFrEF LVEF </= 40%: ARNI in NYHA II-III; ACEi or ARB in NYHA II-IV; beta blocker, MRA, SGLT2i, diuretics as needed
ISDN/hydralazine (Class I Evidence A if black and persistently symptomatic on GDMT); ISDN/hydralazine (Class IIa Evidence B if ARNI/ACEI/ARB intolerant); Ivabradine (Class II Evidence B-R); Digoxin (Class IIa Evidence B if persistently symptomatic on GDMT)
Diuretics: General Treatment Concepts
- Diuretics are a cornerstone of HF treatment
- All HF patients with signs/symptoms of fluid retention (SYMPTOMATIC) should be managed with diuretics: Diuretics reduce hospitalizations but do not have an impact on mortality or natural progression of HF; Reduce symptoms associated with fluid overload, improve exercise tolerance and improve QOL; Lowest dose that maintains euvolemia
- Patients who do not have symptoms of volume overload should not receive diuretics (electrolyte imbalance; blood volume dcreases, sympathetic nervous system is activated –> futher perpetuates HF)
Diuretics
- Short term benefits: Reduce fluid retention via…decreased edema, pulmonary congestion and JVD by reducing preload and cardiac filling pressure.
- Longer term benefits: Reduced daily symptoms and improve ability to exercise
- MOA: Increase sodium and water excretion by reducing sodium reabsorption at a variety of sites in the nephron.
- Must get to their site of action to elicit a pharmacologic response.
Diuretics inhibit Cl- binding on site on protein, too big to be absorbed, so block absorption of NaCl
Loop Diuretics
- Potent diuretics block Na and Cl reabsorption in the ascending limb of the LOH (20-25 % of filtered Na is reabsorbed)
- Loop diuretics additional benefits: Enhancing renal release of prostaglandins (increases renal
blood flow and enhancing venous capacitance); Blocked by NSAIDS - Patients with impaired renal function may require higher doses
- Furosemide has erratic bioavailability, torsemide may have an advantage in some patients: Must be considered when switching agents
Loop diuretics in HF
furosemide, bumetanide, torsemide, ethacrynic acid
IV equivalent doses for loop diuretics
F 40 mg = B 1 mg = T 20 mg = E 50 mg
Thiazides and Thiazide-Like Diuretics
- Relatively weak agents, block Na and Cl reabsorption in the DCT
- THZs may be used in patients with mild HF and small amounts of fluid retention.
- THZs (like all diuretics) lose effectiveness as renal function decreases: Higher doses are generally necessary when GFR is decreased (< 30 mL/min)
- MTZ is erratically absorbed and has a long half-life
- HCTZ and MTZ are frequently used in combination with loop diuretics in patients who become resistant to single-drug therapy.
Thiazides and thiazide-like diuretics in HF
HCTZ, metolazone, chlorthalidone, CTZ, indapamide
Potassium Sparing Diuretics
- Weak diuretics: Generally only used in patients who require potassium “sparing”
- Spironolactone and eplerenone are traditionally
thought of as potassium sparing diuretics.
SE: hyperkalemia
Adverse Effects of thiazides and loops
- ↓Mg+2
- ↓K+
- Volume depletion, ↓ renal fx, pre- renal azotemia
- ↓Na+
- Postural hypotension
- ↑Uric Acid
- ↑Ca+2 (thiazides) or ↓Ca+2 (loops)
Loop Diuretics Initiation
- Initiate at low-doses, then double and titrate: Renal function/previous use important in initial selection
- Dosage adjustments based on weights and symptoms
- If fluid overload, reduce weight 1-2 pounds/day (1L of fluid)
- Patients should report if there is weight gain (e.g. 3-5 pounds/week)
- Hypotension and increased SeCr or BUN/Cr ratio may be indicative of volume depletion (15:1 = normal, <20:1 = dehydrated)
- Dose adjustments may be required during ACEI/ARB/ARNI and/or Beta-blocker titration
Diuretics Use and Monitoring Parameters
- Combine with GDMT
- Start with low dose and double based on weight and diuresis: 1-2 pounds/day if patient has fluid overload
- Monitoring: 1-2 weeks after initiation and increase: Fluid intake and urinary output; Body weight; S/S of congestion, JVD; Blood pressure; Serum electrolytes (especially K and Mg); Replace K (>4.0 mEq/L) and Mg (>2.0 mEq/L) as necessary; Renal function
Consensus Panel Recommendations for diuretics
stage B: asymptomatic reduced ejection fraction don’t get diuretics (if have HTN + rEF and already on HCTZ, then could use)
stage C: everyone with sx at lowest possible dose to maintian euvolemia; use forever
