Once patients have developed structural heart disease their therapy depends on the NYHA functional classification.
NHYA Functional Classification
Etiology:
Depressed EF (<60%)
CAD
Myocardial infarction and ischemia (etio for both HF with depressed EF and heart failure with preserved EF), responsible for 60-75% of cases of HF.
Chronic pressure overload
HTN
Obstructive VHD
Both CAD + HTN interact to augment risk of HF, so does DM.
Chronic volume overload
Regurgitant VHD
Inntracardiac L > R shunt
Extracardiac shunting
Non-ischemic, dilated or idiopathic CM - 20-30% etiology not known
Familial/genetic d/o inherited as autosomal dominant. Mutations of genes encoding cytoskeletal proteins (desmin, cardiac myosin, vinculin) and nuclear membrane proteins (lamin) have been identified.
Infiltrative d/o (both systolic and diastolic HF)
amyloidosis
sarcoidosis
Toxins: alcohol, cocaine, chemotherapy
Metabolic disorders
Viral
Chagas' disease
Disorders of rate and rhythm
Chronic bradyarrhythmias
Chronic tachyarrhythmias
Preserved EF (>40 - 50%)
HCM
HTN
Aging
Restrictive CM
Infiltrative d/o (both systolic and diastolic HF)
amyloidosis
sarcoidosis
Storage diseases
hemochromatosis
Fibrosis
Endomyocardial d/o
Pulmonary Heart Disease
Cor pulmonale
Pulmonary vascular d/o
High Output States
Metabolic d/o
Thyrotoxicosis
Nutritional d/o (beriberi)
Excessive blood flow requirements
Systemic AV shunting
Chronic anemia
Precipitating factors: dietary and medication non-compliance, MI, HTN, AF, Infections, anemia, volume overload, alcohol/toxins, thyroid disease, PE, drugs: (NSAIDs, CCB like diltiazem and verapamil, Class I antiarrhythmic agents, doxorubicin), PE, aortic valvular insufficiency, pregnancy.
History
Dyspnea on exertion and/or rest
Fatigue
Exercise intolerance
Orthopnea, PND, nocturnal cough.
PND usually occurs 1-3 hrs after the patient sleeps. Manifests as coughing, wheezing, gasping for breath. May continue even when patient has assumed an upright posture.
Systemic or pulmonary vascular congestion (LE edema or cough/wheezing)
Cheyne-Stokes respiration. a.k.a periodic respirations or cyclic respirations. Common in advanced HF, usually associated with low CO. Caused by diminished sensitivity of the respiratory center to arterial PCO2. Characterized by apneic phase, during which arterial PO2 falls and PaCO2 rises, which in turn stimulates the respiratory center to kick in, resulting in hyperventilation and hypocapnia, followed by recurrence of apnea.
Presyncope, palpitations, and angina may also be present.
Nocturia
Extreme decompensation presents as hypoperfusion of vital organs with renal failure (decreased UO), mental status changes (confusion and lethargy), and cardiogenic shock.
JVD, +ve HJR. Sustained and prolonged left parasternal heave extending throughout systole - right ventricular hyptertrophy.
Diminished carotid upstrokes
Pulmonary crackles
Cardiomegaly
Acute pulm. edema
S3 (protodiastolic gallop), holosystolic murmur of TR or MR
S4 is not specific indicator of HF but is usually present in patients with diastolic dysfunction.
increased venous pressure (>6 cm H20)
Anorexia, nausea, early satiety, abdominal pain and fullness, RUQ due to congestive hepatomegaly and ascites.
Pleural or pericardial effusion
Vital capacity reduced by 1/3 from normal
Tachycardia equal or more than 120 bmp.
Cerebral hypoperfusion: confusion, disorientation, sleep and mood disturbances
Labs:
CBC, electrolytes, BUN, Cr, Ca, Mg, Phos, FPG, LFTs, Fasting lipids, UA, and TSH.
BNP (>400 is consistent w/ hf), however specificity is reduced in pts with renal failure. Sr. BNP <100 r/o hf.
New-onset HF need additional labs: HIV, hepatitis, hemochromatosis. If rheumatological diseases is suspected (ANA, ANCA, etc.), amyloidosis (SPEP/UPEP), or pheochromocytoma should be considered.
ECG to check for evidence of ischemia (ST-T wave abnormalities), previous MI (Q waves), conductions delays, and arrhythmia ((SVT and VT)
CXR, TTE, Exercise ECG, C.cath with ventriculography, MRI, Right heart cath with PA cath +/- vasodilator challenge for pulmonary HTN, endomyocardial bx.
Coronary angiography should be done in pts with angina or evidence of ischemia on ECG or stress testing unless the patient is not a candidate for revascularization.
Pt. going for heart transplantation should have exercise testing with measurement of peak oxygen consumption to determine the functional capacity.
Tx:
Vasodilators, beta-adrenergic blockers, and diuretics for volume overload.
BB ( Carvedilol, metoprolol, bisoprolol)
Carvedilol, 3.125 mg PO q12h (target: 25 - 50 mg PO q12h)
Metoprolol, 12.5 - 25 mg PO daily (200 mg PO daily)
Bisoprolol, 1.25 mg PO daily (10 mg PO daily)
Typicall 2-3 months of therapy required to observe significant beneficial effects on LV function, but reduction in cardiac arrhythmia and SCD occur much earlier.
Vasodilator therapy is the mainstay of treatment in patients with HF. The RAAS and sympathetic nervous system, as well as increased secretion of arginine vasopressin increase arterial vasoconstriction (afterload) and venous vasoconstriction (preload) in patients with HF. In the absence of LVOT obstruction, arterial vasodilators reduce afterload by decreasing SVR, resulting in increased CO, decreased ventricular filling pressure, and decreased myocardial wall stress. Should be used with caution in patients with a fixed cardiac output (AS or HCM or with predominantly diastolic dysfuncion)
ACEI:
Attenuate vasoconstriction, vital organ hypoperfusion, hyponatremia, hypokalemia, and fluid retention attributable to compensatory activation of RAAS. They antagonize the RAAS by blockade of angiotensin converting enzyme that facilitates conversion of angiotensin I> angiotensin II.
They improve sx and survival in Pts with LV systolic dysfx.
ACEI prevent development of HF in Pts with ASx LVS dysfx and in those at high risk of developing structural heart disease or HF sx (i.e., Pts. with CAD, DM, HTN).
Most ACEI are excreted by kidneys, so careful dosing in Pts with renal insufficiency. Hyperkalemia and acute renal insufficiency may occur in Pts with bilateral renal artery stenosis.
Adverse effects include rash, angioedema, dysgeusia, increased in Sr. Cr, proteinuria, hyperkalemia, leukopenia, and cough.
Caution use of oral potassium supplements, potassium salt substitutes, and potassium sparing diuretics when using ACEI.
Agranulocytosis and angioedema are more common with captopril than with other ACEI, particularly in patients with associated collagen vascular disease or serum creatinine >1.5 mg/dL.
ACEI and ARBs are C/I in pregnancy.
A2RB:
Antagonise RAAS by specific blockade of angiotensin II receptor.
Valsartan and Candesartan are the only U.S.F.D.A approved A2RB in Tx HF.
Used when ACEI are not tolerated.
ARBs are C/I in pregnancy.
Less cough, as they do not increase bradykinin levels as much as ACEI.
Hyperkalemia and acute renal failure can occur if used in renal insufficiency may occur in Pts with bilateral renal artery stenosis.
Renal function and potassium levels should be periodically monitored.
Hydralazine:
Vasodilation by acting directly on arterial smooth muscle to produce vasodilation and to reduce afterload.
Improves survival when used in combination with nitrates in patients with HF.
Causes headaches due to vasodilatory effect in most patients.
Reflex tachycardia and increased myocardial oxygen demand can occur, so caution is used in IHD.
Hydralazine + isosorbide dinitrate (Bidil) 37.5/20 mg PO tid when added to standard therapy with BB, and ACEI has been shown to lower mortality in African Americans.
Nitrates are venodilators, reduce sx of venous and pulmonary congestion. They reduce myocardial ischemia by decreasing ventricular filling pressures and by directly dilating coronary arteries. Nitrate therapy may precipitate hypotension in patients with reduced preload.
Nitroglycerin is the preferred vasodilator for treatment of HF in the setting of acute MI or unstable angina. Potent venodilatory than arterial dilator. Relieves pulmonary and systemic venous congestion and is an effective coronary vasodilator.
Sodium nitroprusside is a direct arterial vasodilator, not so much venodilator. Reduces afterload, effective in HF with HTN or AI or MR. Caution in IHD, potential for coronary steal syndrome (diminution in regional myocardial blood flow)
0.25 mcg/kg/min titrated upto a maximum of 10 mcg/kg/min, to the desired effect or until hypotension develops.
Half life is 1 - 3 minutes, releases cyanide that is metabolized by liver into thiocyanate and then excreted via the kidney. Toxic level of thiocyanate >10 mg/dL, may develop in patient with renal insufficiency. Usually manifests as nausea, paresthesiae, mental status changes, abdominal pain, and seizures. Methemoglobinemia is a rare complication of treatment with nitroprusside.
Recombinant BNP (niseritide) is both arterial and venous vasodilator.
Reduces right atrial, LVEDP, SVR, and results in increase in cardiac output.
2 mcg/kg IV bolus, followed by infusion starting at 0.01 mcg/kg/min. Used in acute HF exacerbations and relieves HF symptoms.
Should not be used to improve renal function or to enhance diuresis.
Not recommended for intermittent outpatient use.
Hypotension is the most common side effect of niseritide. Avoid if SBP <90 or evidence of cardiogenic shock.
Episodes of hypotension managed by D/C niseritide and fluid boluses for volume expansion or pressor support.
Enalaprilat 1.25 mg IV q6h (max 5 mg IV q6h). Patients on diuretics or serum Cr >3 mg/dL, CrCl <30 mL/min, should initially receive 0.625 mg IV q6h. To convert IV to PO, enalaprilat 0.625 mg IV q6h = enlapril, 2.5 mg PO daily.
Alpha-Adrenergic receptor antagonist have not been shown to improve survival in HF, and HTN Pts treated with doxazosin as first-line therapy had an increased risk of developing HF.
Digoxin decreases the number of HF hospitalizations without improving overall mortality. Do not D/c digoxin in patients who are stable on a regimen of digoxin, diuretics, and an ACEI. Clinical deterioration may occur.
0.125 - 0.25 mg and should be decreased in patients with renal insufficiency. Serum digoxin levels of 0.8 - 2 ng/mL are considered "therapeutic" but toxicity can still occur in this range.
Toxic/therapeutic ratio is narrow, serum levels must be followed closely, particularly in Pts with unstable renal function. Pts with higher serum digoxin levels (1.2 - 2 ng/mL) have an increased mortality risk.
Drug interactions with digoxin are common. Erythromycin, tetracycline, quinidine, verapamil, flecainide, and amiodarone increase digoxin levels significantly. Hypokalemia increases digoxin toxicity. Hypoxemia, hypothyroidism, renal insufficiency, and volume depletion increaed digoxin toxicity.
Diuretic therapy
Thiazides (HCTZ, chlorthalidone)
Metolazone
Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid)
Potassium-sparing diuretics
Spironolactone
Eplerenone
Inotropic agents
Sympathomimetic agents
Dopamine
Dobutamine
Phosphodiesterase inhibitors
Digoxin is recommended for patients with symptomatic LV systolic dysfunction who have AF, and it should be considered for Pts who have signs or symptoms of HF while receiving standard therapy, including ACEI and BB. Therapy with digoxin is commonly initiated and maintained at a dose of 0.125 - 0.25 mg PO daily. Serum digoxin should be <1 ng/mL, especially in elderly patients, those with impaired renal function, and a low lean body mass. Loading dose of digoxin not needed.
Diastolic dysfunction:
Known as HF with preserved EF.
Abnormality in mechanical function of heart during diastole or relaxation phase of cardiac cycle.
As ventricular compliance begins to dencrease, as in early stages of ventricular hypertrophy, the EDP rises, but the EDV remains unchanged. The increase in the EDP reduces the pressure gradient for venous inflow into the heart, and this eventually leads to a decrease in EDV and a resultant decrease in the cardiac output.
Elevated filling pressures and impairment of ventricular filling
Diastolic heart failure is a syndrome of HF in the presence of preserved systolic function.
1/2 of HF admissions to hospital
More seen in elderly females, HTN, DM, CAD, AF, HCM, RCM, constrictive pericarditis, infiltrative CM
Dxtic: TTE
Tx: Diuretic with caution. Treat precipitating causes
Treatment of chronic heart failure with depressed EF <40%
Treat fluid retention before starting ACEI or ARB and BB
If Pt. remains symptomatic an ARB, aldosterone antagonist, or digoxin can be added.
Hydralazine + isosorbide dinitrate should be added to ACEI and BB in AA pts with NYHA class II - IV HF. Acts by increasing NO in the peripheral circulation.
Pts intolerant to ACEI and ARB may be given hydralazine and isosorbide dinitrate.
Aldosterone antagonists are not recommended when serum creatinine is >2.5 mg/dL or CrCl <30 mL/min or when the serum potassium is >5 mmol/L. Spironolactone if causes painful gynecomastia may be substituted for eplerenone.
ICD in addition to pharmacological therapy, in NYHA class II-III
CRT in addition to pharmacological therapy, in NYHA class III-IV and QRS >120 ms
Peak oxygen uptake VO2 <14 mL/kg/min is associated with poor prognosis. Pt. with VO2 <14 mL/kg/min have better survival when transplanted than when treated medically.
Fluid restriction is not necessary unless Pt develops hyponatremia with Sr. Na: <130 mEq/L. Recommend <2 L/day.
Titration of ACEI can be done rapidly, whereas titration of BB done gradually in 2 week intervals.
Optimize dose of diuretics prior to starting therapy with BB.