cardiology2 Flashcards
Quinidine
class 1a Na channel blocker, also blocks K particularly well, thereby prolonging action potential duration and it is a vagal inhibitor (anti-cholinergic) as it is a alpha-adrenergic receptor.
Procainamide
class 1a Na channel blocker
Disopryamide
class 1a Na channel blocker
Lidocaine
most important class 1b Na channel blocker in treating arrhythmias, shortens phase 2, increases refractory period.
Mexiletine
class 1b Na channel blocker, shortens phase 2, increases refractory period.
Phenytoin
class 1b Na channel blocker, shortens phase 2, increases refractory period.
Propafenone
class Ic Na channel blockers
Flecainide
class Ic Na channel blockers
Encainide
class Ic Na channel blockers, no longer marketed
Propranolol
beta blocker (class II), reduces L-type Ca current and K current.
Metoprolol
beta blocker (class II), reduces L-type Ca current and K current.
Esmolol
beta blocker (class II), reduces L-type Ca current and K current.
Ibutilide
K channel blockers (class III)
Dofetillide
K channel blockers (class III)
Amiodarone
K channel blockers (class III), also markedly reduces conduction velocity and increases refractory period by blocking Na channels. Also decreases the rate of diastolic depolarization (phase 4) in automatic cells, thus reducing firing rate
Sotalol
K channel blockers (class III), is also a beta blocker
Bretylium
K channel blockers (class III)
Verapamil
use dependent blockers of L-type Ca channels.
Ditiazem
use dependent blockers of L-type Ca channels.
Lisinopril
ACEI
Enalapril
ACEI
Benazepril
ACEI
Valsartan
ARB
Candesartan
ARB
Losartan
ARB
Spironolactone
aldosterone receptor blocker
Eplerenone
aldosterone receptor blocker
Carcedilol
beta blocker (class II), reduces L-type Ca current and K current.
Bisoprolol
beta blocker (class II), reduces L-type Ca current and K current.
Spironolactone
mineralocorticoid receptor
Eplerenone
mineralocorticoid receptor
Digoxin
Digoxin’s primary mechanism of action involves inhibition of the Na+/K+ ATPase, mainly in the myocardium. This inhibition causes an increase in intracellular sodium levels, resulting in a reversal of the action of the sodium-calcium exchanger, which normally imports three extracellular sodium ions into the cell and transports one intracellular calcium ion out of the cell. The reversal of this exchange causes an increase in the intracellular calcium concentration that is available to the contractile proteins. Increased intracellular calcium lengthens phase 4 and phase 0 of the cardiac action potential, which leads to a decrease in heart rate. Increased amounts of Ca2+ also leads to increased storage of calcium in the sarcoplasmic reticulum, causing a corresponding increase in the release of calcium during each action potential. This leads to increased contractility (the force of contraction) of the heart without increasing heart energy expenditure.
Furosemide
diuretic
Bumetanide
diuretic
Torsemide
diuretic
Nesirtide
vasodilator
Diuretics
Furosemide. Often used first to reverse sodium and fluid retention and relieve signs or symptoms of volume overload (dyspnea and peripheral edema). Loop diuretics preferred because of efficacy, but can augment with a thiazide diuretic. Can be used chronically and acutely. Most commonly used is furosemide, but some patients respond better to torsemide or bumetanide due to better and more reliable absorption
Angiotensin Converting Enzyme Inhibitors (ACEIs)
Lisinopril. Started during or after the optimization of diuretic therapy – low doses-> titrated to goal. Produce vasodilation and decreased aldosterone activation plus antiremodeling effect. Angiotensin II Receptor Blockers (AT-1) (ARBs) can be used in patients intolerant to ACEIs (most often due to cough), but NO apparent benefit from dual therapy with ACEI and ARB
Aldosterone Antagonists
Spironolactone. Added to therapy for NYHA class II with LVEF < 30% optimized on ACEI/ARB and beta-blocker therapy or NYHA class III-IV with LVEF < 35%. Must be carefully monitored for serum potassium (< 5.0) and renal function (GFR > 30 ml/min). Blocks aldosterone effect on kidney producing additional sodium loss (since ACEI and/or ARB block of aldosterone action is incomplete) plus antiremodeling effect. If endocrine side effects occur with spironolactone, can use Eplerenone.
Introduction to diurectics
Diuretic agents are best understood in relation to their site of action in the nephron and the normal physiology of that particular segment. Nearly all diuretic agents exert their effects at luminal (urine) surface of renal tubule cells.
Mechanisms include: Interactions with membrane transport proteins (thiazides, furosemide, triamterene), Specific interactions with enzymes (acetazolamide) or hormone receptors (spironolactone), and Osmotic effects preventing water reabsorption (mannitol). Na+ is the major extracellular cation and its movement between compartments is controlled by regulated active transport via Na+-K+-ATPase activity at the interstitial (blood) surface. This enzyme produces the gradient necessary for Na+ reabsorption from the urine back into the blood. However, no diuretics act via inhibition of Na+-K+-ATPase. The diuretic agents decrease Na+ reabsorption at the indicated sites in the nephron below and, as a result, increased amounts of Na+ (and other ions) enter the urine along with H2O entering passively to maintain osmotic equilibrium.
Sites of Acetazolamide Diuretic Action
acts on proximal convoluted tubule in the cortex
Sites of Aldosterone antagonists Diuretic Action
acts on the collecting tubule in the cortex
Sites of ADH antagonists Diuretic Action
acts on the collecting duct in the medulla
Proximal Convoluted Tubules
Almost all of glucose, amino acids, NaHCO3, and other metabolites are reabsorbed here. 60-70% of Na+ reabsorbed (Cl- and H2O follow passively). Presence of H+ ion and the enzyme carbonic anhydrase (CA) on luminal surface allows for reabsorption of HCO3- (and exchange of H+ for Na+). Inhibition of CA by acetazolamide results in retention of HCO3- in lumen (urine) with mild alkaline diuresis. Site of organic acid (diuretics, antibiotics) and base (procainamide) secretion. Important site for delivery of diuretics to their specific site of action in nephron and for potential drug-drug interactions.
Carbonic Anhydrase Inhibitors
Acetazolamide (Diamox), Dorzolamide, Brinzolamide
Pharmacodynamics of carbonic anhydrase inhibitors
Inhibition of carbonic anhydrase enzyme depresses NaHCO3 reabsorption in proximal tubule. Also inhibits formation of aqueous humor and CSF that is dependent on HCO3- transport
Pharmacokinetics of carbonic anhydrase inhibitors
Well absorbed orally; effects within 30 min that persist for 12 hrs; secreted into proximal tubule
Clinical Uses of carbonic anhydrase inhibitors
Major use is NOT as diuretic agent and NOT used in heart failure. Glaucoma: Topical administration for chronic open angle glaucoma. Acute mountain sickness. Systemic administration slows progression of pulmonary or cerebral
edema via decrease in formation and pH of cerebrospinal fluid
Adverse Reactions / Toxicities of carbonic anhydrase inhibitors
Minor: Loss of appetite, drowsiness, confusion, tingling in extremities, hypersensitivity rxns. Hyperchloremic metabolic acidosis, renal stones (via increase in urinary pH), K+ wasting
Loop of Henle (thick ascending limb)
Water removal (from lumen) occurs in descending limb as a result of hypertonic osmotic forces generated in interstitial spaces. H2O removal opposed if impermeable solutes present (HCO3-, glucose, osmotic diuretics). Ascending limb is impermeable to H2O, but active NaCl reabsorption occurs in ascending limb via Na+-K+-2Cl- cotransporter (NKCC2 on the luminal side). Although cotransporter itself is electrically neutral, action leads to excess intracellular K+ which then back diffuses into lumen creating a lumen positive potential. This potential then drives the reabsorption of cations Mg++ and Ca++.
Pharmacodynamics of Loop of Henle Agents (High Ceiling Diuretics)
Inhibit NaCl transport (Na+-K+-2Cl–transporter) in thick ascending limb of loop of Henle. Loop diuretics have greatest diuretic effect because of large capacity of this segment. Associated with increase in Mg++, Ca++ excretion (diminish lumen-positive potential). Increase renal blood flow (via effect on renin-angiotensin and prostaglandin systems). Retain substantial diuretic effect even if renal function is compromised.
Pharmacokinetics of Loop of Henle Agents (High Ceiling Diuretics)
Rapidly absorbed orally; extremely rapid IV diuretic response. Handled by renal secretion and filtration. Duration of effect 2-3 hrs for furosemide, 4-6 hrs for torsemide, 6 hours for bumetanide
Clinical Uses of Loop of Henle Agents (High Ceiling Diuretics)
Congestive heart failure - Preferred diuretic class because of greater efficacy. Used in HF patients with volume overload - goal of eliminating signs of fluid retention (pulmonary congestion - peripheral edema). Efficacy of diuretics is enhanced with salt restriction (< 2 g/day). Furosemide is most commonly used. If lack of response can increase dose of furosemide or can switch to bumetanide or torsemide (more reliable bioavailability with both and longer duration of activity with torsemide). IV administration may be required initially in some patients due to congestion-related interference with oral absorption. Patients with HF have reduced diuretic response related to decreased drug delivery to kidney due to decreased RBF and hypoperfusion activation of RAAS and SNS. Refractory edema– A thiazide (metolazone) can be added to therapy if a loop diuretic produces insufficient diuresis. Thiazide action to block distal tubule Na+ reabsorption can counter loop-induced increases in Na+ delivery and reabsorption at that segment. Note that thiazides can add to loop-induced hypokalemia so careful monitoring of serum potassium is warranted with initiation of therapy. An aldosterone antagonist (spironolactone) is recommended in some patients with systolic HF to improve survival. Its actions at the collecting tubule will also enhance diuresis and ameliorate the potassium wasting. Acute pulmonary edema. Rapid reduction of extracellular fluid and venous return (extra-renal hemodynamic response via decrease in RV output and pulmonary vascular pressure). Refractory edema. Loop diuretics used if no response to Na+ restriction or thiazide diuretic; especially useful if renal disease and fluid overload present. Hypercalcemia. Given with saline infusion to prevent extracellular fluid (ECF) volume depletion
Adverse Reactions / Toxicities of Loop of Henle Agents (High Ceiling Diuretics)
Hypokalemic metabolic alkalosis via enhanced secretion of K+ and H+. More pronounced than with thiazides. Hypokalemia predisposes patients to ectopic pacemakers and arrhythmias. Ototoxicity. Especially for ethacrynic acid (also higher incidence with concomitant use of aminoglycoside antibiotics) and if diminished renal function present; usually reversible. Hyperuricemia / hyperglycemia. Hypomagnesemia. Overdose. Rapid blood volume depletion -> dizziness, headache, orthostatic hypotension
Distal Convoluted Tubules
Segment is relatively impermeable to H2O. NaCl reabsorption occurs via an electrically neutral Na+/Cl- cotransporter (pharmacologically distinct from Loop cotransporter). Site of active Ca++ reabsorption via a Na+/Ca++ exchanger. This process is regulated by parathyroid hormone (PTH). This exchanger is not present at the loop of Henle and results in important differences in calcium excretion effects between diuretic classes.
Pharmacodynamics of Thiazide Diuretics
Thiazide diuretics act by inhibiting the Na+/Cl- cotransporter and increasing urinary excretion of NaCl (modest diuretic effect, only 5-10% of filtered Na+ is reabsorbed here). In contrast to loop diuretics, thiazides increase reabsorption of Ca++ (lowering of intracellular Na+ drives Ca++ exchanger or decreased blood volume increases absorption at PCT)
Pharmacokinetics of Thiazide Diuretics
All absorbed well orally (if GI upset, can take with food or milk); best to take early in day. Differences in metabolism / excretion: Hydrochlorothiazide (Hydrodiuril): Prototype thiazide, twice daily dose. Chlorthalidone - Metolazone: longer durations-> once daily dosing. All secreted by organic acid secretory system; competition with uric acid secretion may precipitate a gout attack
Clinical Uses of Thiazide Diuretics
Congestive heart failure. Higher doses needed than in hypertension and more efficacious diuretics are usually required (i.e., loop diuretics). True synergistic diuretic effect with loop diuretics (esp. metolazone) may be useful in refractory edema. Hypertension: First line for mild hypertension (esp., blacks, elderly, obese). Hypercalcuria: Reduced urinary excretion of Ca++ decreases incidence of kidney stones
Adverse Reactions / Toxicities of Thiazide Diuretics
Hypokalemia, can result in weakness, paresthesias, cardiac sensitization (predisposition to ectopic pacemakers), thus use not advisable in patients with arrhythmias, history of myocardial infarction, pre-infarction angina. Volume contraction may lead to secondary hyperaldosteronism. Impaired carbohydrate tolerance (dose-related): hyperglycemia, glucosuria [(?) via impaired pancreatic insulin release (opens K+ channel) or decreased peripheral utilization]. Hyperuricemia. Avoid in patients with gout. Hyperlipidemia. Complicating factor if used long-term for hypertension. Allergic reactions. Skin rashes occasionally, related to sulfonamide component; some cross- allergenicity with sulfonamides
Collecting Tubules
Site of regulation by the mineralocorticoid aldosterone. Only 2-5% of NaCl reabsorption occurs at this site (thus only weak diuretic action possible), but as the most distal site it has important role in determining final urinary Na+ (and ultimately K+ and H+) concentration. Na+ (and H2O) and K+ transport occurs in principal cells via separate channels that exclude anions. The driving force for Na+ entry into cell exceeds that for K+ exit so lumen becomes negative, driving Cl- into cells and K+ into urine. Thus, K+ excretion is coupled to Na+ reabsorption and ALL diuretics that cause a greater delivery of Na+ (and greater tubular flow) to this site will enhance K+ excretion. Aldosterone, through effects on gene transcription, increases the number and activity of both Na+ (ENaC) and K+ membrane channels and the Na+-K+-ATPase. Diuretics that block the Na+ channel (triamterene and amiloride) or antagonize the aldosterone receptor (spironolactone - eplerenone) will decrease Na+ reabsorption and decrease K+ excretion (known as “potassium-sparing” diuretics)
Pharmacodynamics Potassium-Sparing Diuretics - Aldosterone Antagonists and Na+-channel Blockers
Spironolactone / Eplerenone. Only mild diuresis possible if used alone. Competitive antagonist at aldosterone receptor, binds to cytosolic receptor preventing enhancement of protein synthesis. Eplerenone reported to have lower affinity for androgen and progesterone receptors. Blocks aldosterone effect at collecting tubule, thus Na+ is not reabsorbed, lumen- potential becomes more positive, thus less K+ and H+ ions move into urine. Promotes only moderate increase in Na+ excretion. Triamterene / Amiloride: Direct effect to block the Na+-channels on collecting duct lumen to decrease Na+ reabsorption (and thus decreases coupled K+ secretion)
Pharmacokinetics of Potassium-Sparing Diuretics - Aldosterone Antagonists and Na+-channel Blockers
Spironolactone (Aldactone): 1-2 doses/day; poor oral absorption. Slow onset of action. Eplerenone (Inspra): Dosed 1-2 times/day orally, metabolized by CYP3A4. Triamterene (Dyrenium) / Amiloride (Midamor): Triamterene metabolized in liver, amiloride excreted unchanged thus given less frequently. Effect within 2-4 hrs, but 1-3 days to maximal effect.
Clinical Uses of Potassium-Sparing Diuretics - Aldosterone Antagonists and Na+-channel Blockers
Congestive Heart Failure: Survival benefits seen with aldosterone antagonists. Most important action is block of aldosterone receptors on heart rather than kidney. Anti-remodeling action - block of deleterious effect of aldosterone on heart-> cardiac hypertrophy and fibrosis. Additional benefits from raising serum potassium to counter risk of hypokalemia- induced arrhythmias resulting from use K+-wasting diuretics (loop and thiazides). Primary hyperaldosteronism (spironolactone and eplerenone). Hirsutism of polycystic ovary syndrome via block of androgen receptor (spironolactone). Hypertension (in combination with thiazides). Spironolactone-HCTZ (Aldactazide), Triamterene-HCTZ (Dyazide)
Adverse Reactions of Potassium-Sparing Diuretics - Aldosterone Antagonists and Na+-channel Blockers
Hyperkalemia-> EKG changes, conduction abnormalities, arrhythmias. Risk increased by: increasing age, underlying renal dysfunction, higher doses, combined use of ACEI or ARB, use of NSAID analgesics. Endocrine abnormalities (gynecomastia) with spironolactone via block of androgen receptor (∼ 10%). NOT seen with eplerenone which is more selective for aldosterone receptors. Mild effects: GI upset, drowsiness
Angiotensin-Converting Enzyme Inhibitors [ACEIs]
Lisinopril (Zestril, Prinivil), Captopril (Capoten), Enalapril (Vasotec), Ramipril (Altace), Quinapril (Accupril), Moexipril (Univasc), Benazepril (Lotensin)
Mechanism of Action in Heart Failure of Angiotensin-Converting Enzyme Inhibitors [ACEIs]
Inhibits ACE conversion of Ang I to Ang II, blocking Ang II-induced vasoconstriction. This results in decreased preload and afterload. However, other vasodilators have less survival benefits than ACEIs suggesting that ACEIs work by other mechanisms. Primary mechanism may be ACEI decrease of Ang II-induced release of aldosterone which moderates the myocardial hypertrophy and remodeling response to aldosterone. Decreases bradykinin inactivation, increasing its vasodilator action. Improve endothelial function via enhancement of nitric oxide action. Reduce sympathetic activity.
Other Uses: Hypertension - first-line therapy and Delay progression of diabetic nephropathy
Pharmacokinetics and Dosing Considerations of of Angiotensin-Converting Enzyme Inhibitors [ACEIs]
All are well absorbed orally; most have reduced absorption if taken with food. All ACEIs, except lisinopril and captopril, are prodrugs that are converted to the active metabolite by de-esterification in the liver. The active metabolites are primarily eliminated by the kidneys (exceptions: moexipril and fosinopril) requiring dosage reduction in patients with renal insufficiency. Duration of action generally sufficient to allow once-daily dosing for most agents.
Side Effects of Angiotensin-Converting Enzyme Inhibitors [ACEIs]
Contraindicated in pregnancy (Category C/D in 2nd and 3rd trimester). Dry cough. Hyperkalemia. Severe hypotension (if hypovolemic), acute renal failure (esp. with renal artery stenosis), angioedema. Neutropenia and proteinuria seen with high doses of captopril – rare with newer agents. Minor effects include altered taste sense, skin rashes
Angiotensin II Receptor (AT1) Antagonists [ARBs]
Losartan (Cozaar), Valsartan (Diovan), Irbesartan (Avapro), Olmesartan (Benicar), Candesartan (Atacand)
Mechanism of Action in Heart Failure of Angiotensin II Receptor (AT1) Antagonists [ARBs]
Selective inhibition of Angiotensin II receptor AT1. Similar to ACEIs, ARBs prevent remodeling and reduce sympathetic activity. Advantage vs ACEIs: Potential for more complete inhibition of angiotensin action since alternative pathways (chymase) exist to form Angiotensin II that are NOT blocked by ACEIs and No side effects mediated by increased bradykinin levels-> cough, angioedema. Disadvantage vs ACEIs: Loss of increased bradykinin actions (vasodilation) that result from ACE inhibition and Block only Ang II actions at AT-1 receptors while decreased Ang II synthesis by ACEIs will block actions mediated by both AT-1 and AT-2 receptors. Other Uses: Alternative in conditions that respond to ACE inhibitors, but ACEIs not tolerated
Dosing Considerations of Angiotensin II Receptor (AT1) Antagonists [ARBs]
All agents are effective orally with once daily dosing except for losartan (twice daily). Decreased losartan dose necessary in hepatic dysfunction.
Side Effects of Angiotensin II Receptor (AT1) Antagonists [ARBs]
Similar to ACEI, contraindicated in pregnancy, but NO angioedema or cough
atrial kick
Atrial systole Cardiology The contraction of the atrium, which accounts for 5-30% of cardiac output; it appears as an abrupt notch in the pressure curve in the ventricular outflow tract, and is typical of hypertrophic cardiomyopathy–formerly idiopathic hypertrophic subaortic stenosis
amyloidosis of the heart
Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction. On echocardiography the heart shows restrictive filling pattern, with normal to mildly reduced systolic function.[4] AA amyloidosis usually spares the heart.
Acute myocarditis
Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. An inflammatory disease of the myocardium that usually attacks a healthy child or adult and is often viral in origin. There is a wide range of presentations. Myocarditis often presents within 2 weeks following development of an upper respiratory infection or a flu-like syndrome with fever and chills or gastrointestinal symptoms. If concurrent pericarditis is present patients may have chest pain as well. Adult cases often present with heart failure with or without cardiogenic shock. Arrhythmias with palpitations or syncope are sometimes the presenting symptoms and may cause sudden death. Acute inflammation of the cardiac muscle that is usually viral in etiology. May be focal or diffuse. Often seen in relatively young adults and children. 50% have preceding respiratory of GI symptoms. Common presentations include fever, chest pain with ECG changes, arrhythmia, and heart failure. The ECG findings most commonly seen in myocarditis are diffuse T wave inversions; saddle-shaped ST-segment elevations may be present (these are also seen in pericarditis). Low ejection fraction and heart failure have high mortality but some recover and others develop a chronic dilated cardiomyopathy.
Causes of myocarditis
Many viruses may cause myocarditis. Hypersensitivity to drugs (anthracyclines and other chemotherapeutic agents most common); Systemic inflammatory diseases (such as systemic lupus erythematosus); and certain bacterial, fungal or other infectious diseases are among less common causes. Peripartum cardiomyopathy which begins the last month of pregnancy or within 5 months after pregnancy is a poorly understood myocarditis that often resolves but may proceed to a serious cardiomyopathy. In cases of viral etiology an immune-related process rather than direct damage from the actual pathogen may be the major mechanism of injury. Certain viruses such as Coxsackie B have a relatively high incidence of myocarditis. However, in any viral epidemic only a very small percentage of victims are afflicted by clinically detectable myocarditis and the reason for this is unknown. One theory is that a genetic predisposition is a major factor enabling the immune-related process. Myocarditis is often an autoimmune reaction. Certain viruses such as coxsackie B have regions (epitopes) that are immunologically similar to cardiac myosin.
Physical findings with myocarditis
Physical findings include a third heart sound (S3), pulmonary congestion or peripheral edema, or if cardiac dilation is present mitral or tricuspid insufficiency murmurs. Increased troponins resembling findings in acute myocardial infarcts may be present. A variety of nonspecific ECG changes may occur including patterns suggestive of pericarditis or acute myocardial infarction. Echocardiograms often demonstrate global or diffuse ventricular dysfunction and are very useful in confirming that a myocardial process is present. Biopsies are rarely done but if obtained show focal or diffuse necrosis and myocyte swelling with inflammatory changes. A large percentage of cases of myocarditis with minimal or absent symptoms other than evidence of an acute viral infection probably go unrecognized. Some such cases may eventually develop a dilated cardiomyopathy. Cases presenting with heart failure may resolve without apparent injury, may proceed rapidly down hill to death or may evolve into a chronic dilated cardiomyopathy.
Treatment of myocarditis with heart failure
If heart failure is present usual methods for this condition are applicable, particularly diuresis, low dose beta blockade and angiotensin converting enzyme (ACE) inhibitors. Occasionally inotropic agents may be a consideration. In nonviral infections appropriate antimicrobial agents are used. In diseases in which steroids are known to effective, such as systemic lupus, they are useful. However, in viral or idiopathic cases steroids are controversial.
Types of cardiomyopathy
There are three types of cardiomyopathy. By far the commonest is a dilated cardiomyopathy. The left ventricle is always involved but in many cases all four chambers of the heart are markedly dilated. Mild hypertrophy with increased cardiac mass is usual. The other two types are rare. In hypertrophic cardiomyopathy the left ventricle is hypertrophied but not dilated, and there often is disproportionate hypertrophy of the septum. In restrictive cardiomyopathy there is infiltration or fibrosis of the ventricles, usually without dilatation.
Causes of dilated cardiomyopathy
There are many causes of dilated cardiomyopathy. Clinically a distinction is often made between “ischemic”, due to coronary artery disease and “nonischemic” dilated cardiomyopathy. Dilation may be present without development of heart failure in mild cases or early stages of the disease. It is usually idiopathic. Can also be caused due to genetics or a virus.
Clinical manifestations of dilated cardiomyopathy
It is commonest to detect this condition when severe heart failure is present. In the presence of heart failure, demonstration by echocardiography of dilation and impaired systolic function of both ventricles (dilated and more spherical, diffuse poor wall motion, low ejection fraction) and chest film show cardiomegaly confirm the diagnosis. Arrhythmia injury fibrosis, and dilation) and thromboembolism (dilation, porr contraction and abnormal surface) are common complications. Sudden death from ventricular arrhythmias may occur. Spherical diffuse poor wall motion, low ejection fraction. BNP is slightly elevated with asymptomatic LV dysfunction and greatly elevated with patients with CHF.
Presentation of dilated cardiomyopathy
Heart failure with a large silent heart with impaired systolic function. Congested lung fields. Dilated poorly contractile LV that is hypokinetic.
Etiology of dilated cardiomyopathy
Usually idiopathic, Ischemic, Familial, Viral, and Other
Treatment of dilated cardiomyopathy
treat heart failure with drugs such as Digoxin, Diuretics, ACE Inhibitors, Beta blockers, Spironolactone, Vasodilators, Inotropes, Biventricular pacing if ventricular asynchrony present. May also need to treat anticoagulation, anti-arrhythmic agents (drugs or implantable defibrillators), or heart transplant. Use of drugs to treat heart failure is needed. Diuretics, beta blockers and ACE inhibitors are usually effective. If ventricular asynchrony is present, often due to left bundle branch block, biventricular pacing may be helpful in refractory cases. Anticoagulation to prevent emboli, particularly if atrial fibrillation is present, is usually advisable. Appropriate antiarrhythmic agents may be needed or in some cases implantable defibrillators to prevent sudden death. As a last resort implantable left ventricular assist devices (LVADs) or heart transplant may be a consideration. Neurohumoral activation to development and reversal of remolding. Myocyte dysfuction and structural alterations are propagated by cardiac adrenergic and RAAS signaling. Improved function and reverse remodeling can by propagated by ACE inhibitors and beta blocker therapy
Hypertrophic cardiomyopathy
Hypertrophy which is often eccentric, predominantly involving the septum, without dilation. Predominant diastolic dysfunction. Normal or enhanced systolic function. Dynamic out flow obstruction may be present. Usually familial. There is a strong genetic component in this relatively rare disease. The left ventricle is hypertrophied but not dilated. The muscle fibers and collagen matrix are disorganized, particularly in the septum which tends to be disproportionately thickened. In some cases the disproportionate intraventricular septal thickening and a hyperdynamic contraction may cause aortic outflow tract obstruction. Especially if obstruction is present, sudden death may occur with exertion. Autosomal dominant inheritance occurs.
Treatment of hypertrophic cardiomyopathy
decrease contractility- beta/calcium channel blockade, surgical resection, avoid extreme exertion, and ventricular pacing. If an obstructive component is present several steps should be taken. Decreasing contractility may decrease the outflow tract obstruction. If drugs are ineffective, surgical resection or percutaneous alcohol septal ablation in the outflow tract often relieves obstruction. Avoiding extreme exertion may prevent sudden death. Ventricular pacing may occasionally be useful for relief of obstruction or arrhythmia control.
Hypertrophic cardiomyopathy without aortic outflow obstruction
diastolic dysfunction due to impaired diastolic relaxation and increased stiffness. Elevated LV diastolic pressure causes increased pulmonary venous and capillary pressure. Dyspnea on exertion usual symptom. No risk for sudden death.
Hypertrophic obstructive cardiomyopathy
asymmetric myocardial hypertrophy, diastolic dysfuction, enhanced systolic dysfunction, dynamic left ventricular outflow obstruction, and propensity for syncope and sudden death. Vasodukator decrease ventricular volume and increases outflow obstruction.
Clinical manifestation of hypertrophic obstructive cardiomyopathy
variable, can be asymptomatic to severe symptoms. dyspnea due to increased LV filling pressure, angina due to hypertophic LV and increased systolic LV pressure, and sudden death due to arrhythmia may also occur. It is by far the main cause of sudden death in athletes from ages 12-35. Sudden death is also the main cause of death in patients with HCM 45 years of age and younger. Later on in life HCM can degrade into HF, which is the main cause of death in older patients. There is also an increased risk in stroke at old age.
Hypertrophic obstructive cardiomyopathy treatment
Avoid competitive sports and other extreme exertion. Decrease contractility–Beta blockers/ Verapamil. Surgical myomectomy or Alcohol ablation. Automatic Implantable Cardiac Defibrillator
Arrhythmogenic myocardial substrate in patients with HCM
disorganized myocytes, remodeled coronary arteriole, and replacement fibrosis
Systolic Anterior Motion of the Mitral Valve
Systolic anterior motion of the mitral valve (SAM) is a paradoxical motion of the anterior, and occasionally posterior, mitral valve leaflet towards the left ventricular outflow tract (LVOT) during systole. The exact mechanism of SAM in hypertrophic cardiomyopathy (HCM) is debated, with some investigators postulating that it is a Venturi effect, while others believe that it is secondary to anatomical differences in the positions of the papillary muscles and valve leaflets. According to the Venturi effect, fluid pressure decreases and velocity increases as fluid flows through a region of reduced cross sectional area. Septal hypertrophy in HCM creates the Venturi effect through reduction in the LVOT diameter, which leads to an increased velocity and reduced pressure of the ejected blood in the LVOT. This pressure differential between the left atrium and the outflow tract is thought to lead to deviation of the mitral valve towards the septum. SAM may alternatively be caused by the more anterior and inward location of the papillary muscles which alters chordal tension, resulting in a push of the leaflets towards the ventricular septum at the beginning of systole. The pathogenesis of SAM is likely a combination of these two mechanisms and varies depending on the underlying associated condition. SAM is most commonly seen in the asymmetric septal form of HCM but has also been described in hypertensive heart disease, diabetes mellitus, acute myocardial infarction, after mitral valve repair, and even in asymptomatic patients during pharmacologic stress with dobutamine.4 Approximately 25% of patients with HCM have dynamic subaortic outflow obstruction occurring at rest caused by SAM contacting the hypertrophied interventricular septum. Current therapies aim to reduce the risk of congestive heart failure through reduction of the LVOT pressure gradient. The hallmarks of therapy are medications (eg, β-blockers and calcium channel blockers), septal myectomy, and transcatheter alcohol ablation of the interventricular septum. The effectiveness of alcohol ablation is evaluated with delayed gadolinium hyperenhancement and VENC phase contrast sequences.9 Reduced septal thickness, resolution of SAM, and reduced pressure gradient across the LVOT indicate a response to treatment. It is important to consider a diagnosis of HCM when SAM is identified in conjunction with asymmetric septal hypertrophy and mitral regurgitation.
Restrictive cardiomyopathy
Most commonly infiltrative: amyloidosis and sarcoidosis. Impaired ventricular filling due to stiff (noncompliant) ventricles. Systolic function often normal and ventricles usually not dilated. Diagnosed by echocardiography with Doppler assessment of ventricular filling. This rare entity has a poor prognosis. Intractable failure and fatal arrhythmias may occur.
Introduction to the ECG
The initial deflection is the P wave, which is due to atrial depolarization. The next deflection is the QRS which is due to ventricular depolarization. The Q is negative, the R is positive and the S is a late negative deflection. One, two, or all of these deflections may be present in a given lead. Normally the duration of the QRS is 0.06-0.10 seconds. The T wave is due to ventricular repolarization. U waves are inconstant. The paper speed is 25 mm/second. Thin vertical lines (small squares) are 0.04 seconds apart and thick vertical lines (large squares) are 0.2 seconds apart. The PR interval from the onset of the P wave to the onset of the QRS is a measure of atrioventricular node conduction time, since most of the interval reflects delay in traversing the node. A normal PR interval is 0.12-0.20 seconds. The QT interval represents the total duration of depolarization and repolarization. Abnormalities in the QT interval and t wave due to drugs, abnormal electrolytes, or other causes predispose to arrhythmias usually through alterations in repolarization
Heart rate and ECG
Paper speed 25mm/sec. Light lines (1mm) 0.04 sec. Heavy lines (5mm) 0.2 sec. HR = 300 ÷ # heavy lines between 2 QRS’s. HR= 1500 ÷ # mm between 2 QRS’s
EKG leads
Leads are electrodes which measure the difference in electrical potential between either: 1. Two different points on the body (bipolar leads). 2. One point on the body and a virtual reference point with zero electrical potential, located in the center of the heart (unipolar leads). Polarity of leads depends on whether the depolarization is moving toward (positive) or away from (negative) the electrode. QRS will be upright (+) in left and lateral leads. And downward (-) in right-sided leads
RA lead
placement is on the right arm, avoiding thick muscle.
LA lead
placement is in the same location as RA but on the left arm
RL lead
placement is on the right leg, lateral calf muscle
LL lead
placement is in the same location as RL but on the left leg
V1 lead
placement is in the fourth intercostal space (between ribs 4 and 5) just to the right of the sternum (breastbone).
V2 lead
placement is in the fourth intercostal space (between ribs 4 and 5) just to the left of the sternum.
V3 lead
placement is between leads V2 and V4.
V4 lead
placement is in the fifth intercostal space (between ribs 5 and 6) in the mid-clavicular line.
V5 lead
placement is horizontally even with V4, in the left anterion axillary line
V6 lead
placement is horizontally even with V4 and V5 in the midaxillary line
Inferior leads
Leads II, III and aVF. Look at electrical activity from the vantage point of the inferior surface (diaphragmatic surface of heart)
Lateral leads
leads I, aVL, V5 and V6. Look at the electrical activity from the vantage point of the lateral wall of left ventricle
Septal leads
leads V1and V2. Look at electrical activity from the vantage point of the septal surface of the heart (interventricular septum)
Anterior leads
leads V3 and V4. Look at electrical activity from the vantage point of the anterior wall of the right and left ventricles (Sternocostal surface of heart)
Axis on ECG
The heart’s electrical axis is the general direction of the ventricular depolarization wavefront (or mean electrical vector) in the sagittal plane (the plane of the limb leads and augmented limb leads). The QRS axis can be determined by looking for the limb lead or augmented limb lead with the greatest positive amplitude of its R wave. A lead can only detect changes in voltage that are aligned with that lead; therefore the lead that is best aligned with the axis of ventricular depolarization will have the tallest positive QRS complex. The normal QRS axis is generally down and to the left, following the anatomical orientation of the heart within the chest. An abnormal axis suggests a change in the physical shape and orientation of the heart, or a defect in its conduction system that causes the ventricles to depolarize in an abnormal way. Left axis deviation may indicate left ventricular hypertrophy, left anterior fascicular block, or an old inferior q-wave myocardial infarction. Right axis deviation may indicate right ventricular hypertrophy, left posterior fascicular block, or an old lateral q-wave myocardial infarction.
ECG of patient with a fixed stenosis of a coronary artery
The resting ST segment is normal but during exercise there is ST depression due to transient ischemia.
P-wave feature
The p-wave represents depolarization of the atria. Atrial depolarization spreads from the SA node towards the AV node, and from the right atrium to the left atrium. The p-wave is typically upright in most leads except for aVR; an unusual p-wave axis (inverted in other leads) can indicate an ectopic atrial pacemaker. If the p wave is of unusually long duration, it may represent atrial enlargement. Typically a large right atrium gives a tall, peaked p-wave while a large left atrium gives a two-humped bifid p-wave. Duration is less than 80 ms.
PR interval
The PR interval is measured from the beginning of the P wave to the beginning of the QRS complex. This interval reflects the time the electrical impulse takes to travel from the sinus node through the AV node. A PR interval shorter than 120 ms suggests that the electrical impulse is bypassing the AV node, as in Wolf-Parkinson-White syndrome. A PR interval consistently longer than 200 ms diagnoses first degree atrioventricular block. The PR segment (the portion of the tracing after the p-wave and before the QRS complex) is typically completely flat, but may be depressed in pericarditis. Duration is 120 to 200 ms.
QRS complex
The QRS complex represents the rapid depolarization of the right and left ventricles. The ventricles have a large muscle mass compared to the atria, so the QRS complex usually has a much larger amplitude than the P-wave. If the QRS complex is wide (longer than 120 ms) it suggests disruption of the heart’s conduction system, such as in LBBB, RBBB, or ventricular rhythms such as ventricular tachycardia. Metabolic issues such as severe hyperkalemia, or TCA overdose can also widen the QRS complex. An unusually tall QRS complex may represent left ventricular hypertrophy while a very low-amplitude QRS complex may represent a pericardial effusion or infiltrative myocardial disease. Duration is 80 to 100 ms.
ST segment
The ST segment connects the QRS complex and the T wave; it represents the period when the ventricles are depolarized. It is usually isoelectric, but may be depressed or elevated with myocardial infarction or ischemia. ST depression can also be caused by LVH or digoxin. ST elevation can also be caused by pericarditis, Brugada syndrome, or can be a normal variant (J-point elevation).
T wave
The T wave represents the repolarization of the ventricles. It is generally upright in all leads except aVR and lead V1. Inverted T waves can be a sign of myocardial ischemia, LVH, high intracranial pressure, or metabolic abnormalities. Peaked T waves can be a sign of hyperkalemia or very early myocardial infarction. Duration is 160ms.
Corrected QT interval
The QT interval is measured from the beginning of the QRS complex to the end of the T wave. Acceptable ranges vary with heart rate, so it must be corrected by dividing by the square root of the RR interval. A prolonged QTc interval is a risk factor for ventricular tachyarrhythmias and sudden death. Long QT can arise as a genetic syndrome, or as a side effect of certain medications. An unusually short QTc can be seen in severe hypercalcemia. Duration is less than 440 ms.
U wave
The U wave is hypothesized to be caused by the repolarization of the interventricular septum. It normally has a low amplitude, and even more often is completely absent. If the U wave is very prominent, suspect hypokalemia, hypercalcemia or hyperthyroidism.
ECG of a patient with an acute clot in a coronary artery
Normally T waves and the QRS go in the same direction. Here the T wave is inverted, a sign of ischemia. This could be transient or result ultimately in tissue injury.
