Cardiology 5 USMLE

Danil Hammoudi.MD

SINOE MEDICAL ASSOCIATION

CARDIOLOGY-VALVULOPATHY AND COMPLICATION

VALVULOPATHY:

MITRAL REGURGITATION

Mitral regurgitation can be divided into the following 3 stages:

Ø acute,

Ø chronic compensated,

Ø chronic decompensated

1. acute stage,

Ø which usually occurs with a spontaneous chordae tendineae rupture secondary to myocardial infarction,

Ø there is a sudden volume overload on an unprepared left ventricle and left atrium.

Ø The volume overload on the left ventricle

§ increases left ventricular stroke work.

§ Increased left ventricular filling pressures,

§ combined with the transfer of blood from the left ventricle to the left atrium during systole, results in elevated left atrial pressures.

§ This increased pressure is transmitted to the lungs resulting in acute pulmonary edema and dyspnea.

Ø If the patient tolerates the acute phase, the chronic compensated phase begins

2. CHRONIC compensated phase

Ø results in eccentric left ventricular hypertrophy.

Ø The combination of increased preload and hypertrophy produces increased end-diastolic volumes,

Ø which, over time, results in left ventricular muscle dysfunction.

Ø This muscle dysfunction impairs the emptying of the ventricle during systole.

Ø Therefore, regurgitant volume and left atrial pressures increase, leading to pulmonary congestion.

Ø rheumatic heart disease remains the leading cause of mitral regurgitation.

The prognosis of patients with mitral regurgitation depends on the underlying etiologies and the state of the left ventricular function.

• Acute pulmonary edema and cardiogenic shock often complicate the course of acute regurgitation.
• The operative mortality in these cases approaches 80%.
• A patient with a ruptured chordae tendineae and minimal symptoms has a much better prognosis.

• With chronic regurgitation, volume overload is tolerated very well for years before symptoms of failure develop.
• Left atrial enlargement predisposes patients to the onset of atrial fibrillation with the subsequent complication of embolization.
• In addition, these patients are susceptible to endocarditis.

• The majority of patients with mitral valve prolapse are asymptomatic.
• Prolapse in those older than 60 years is frequently associated with chest pain, arrhythmias, and heart failure.
• The prognosis of these patients is good; however, sudden death, endocarditis, and progressive regurgitation do occur rarely.

• When ischemic heart disease is the mechanism for regurgitation, the extent of anatomic disease and left ventricular performance are prognostic determinants.
• Complicating events include sudden death and myocardial infarction.

History:

• Mitral regurgitation can be tolerated for many years.

• The initial symptoms of dyspnea and fatigue can rapidly progress to orthopnea and paroxysmal nocturnal dyspnea.

• Patients with anginal-type pain may have underlying ischemia.

• Atypical chest pain can be associated with mitral valve prolapse syndrome.

• In those with mitral valve prolapse, palpitations and atypical chest pain are the most frequent complaints. Two-thirds of these patients are female, often with an underlying panic disorder.

• With underlying coronary artery disease (CAD), regurgitation usually is associated with symptoms of angina pectoris.

• Regurgitation also can develop acutely with myocardial infarction, secondary to papillary muscle rupture.

• CAD is often accompanied by dyspnea, fatigue, orthopnea, and fluid retention. Chest pain is usually minimal in these patients.

• When mitral regurgitation is due to left ventricular dilatation and altered valve function, patients often have chronic left-sided heart failure.

• In acute mitral regurgitation from sudden disruption of the mitral valve, the symptoms are due to acute pulmonary edema.

Physical:

• The classic murmur of mitral regurgitation is a high-pitched holosystolic murmur beginning with the first heart sound and extending to the second heart sound.

• The intensity usually is constant throughout systolic ejection, often radiating to the axilla.

• The harshness of the murmur does not correlate with the magnitude of the valvular defect.

• Those patients with severe disease often have a third heart sound, a consequence of the increased ventricular filling volume that is ejected into the left ventricle under higher than normal pressure.

• Patients with mitral valve prolapse often have a mid- to late systolic click and a late systolic murmur. These patients are usually female and often have orthostatic hypotension.

• Patients with CAD can have the above mentioned murmur any time during systole, accompanied by an atrial gallop.

• In acute mitral regurgitation, the exam is usually consistent with acute pulmonary edema and left ventricular failure.

• The heart size is usually normal, but there often is an audible systolic thrill.

• The murmur is often harsh. It may be heard over the back of the neck, vertebra, and/or sacrum, and it may radiate to the axilla, back, and left sternal border.

Causes:

• Acute rheumatic heart disease remains a significant consideration in those with mitral regurgitation and are younger than 40 years of age.

• Mitral valve prolapse (ie, myxomatous degeneration) accounts for approximately 45% of the cases of mitral regurgitation in the Western world.

• The causative agent is unknown in this condition.

• Myxomatous degeneration is usually a slow process, with a major complication being the rupture of the chordae tendineae.
• Acute regurgitation, as mentioned earlier, can be caused by a chordae tendineae rupture or papillary muscle dysfunction.

• The literature now seems to suggest that mitral valve prolapse has become the most common cause of mitral regurgitation in the adult population.

• In addition, mitral valve prolapse and CAD have become major mechanisms for incompetence of the mitral valve.

• Ischemia is responsible for 3-25% of mitral regurgitation.

• The severity regurgitation is directly proportional to the degree of left ventricular hypokinesis.

• Mitral annular calcification can contribute to regurgitation. Impaired constriction of the annulus results in poor valve closure.

• Left ventricular dilatation and heart failure can produce annular dilatation and poor valve closure resulting in mitral regurgitation.

• Tendineae rupture can be due to endocarditis, myocardial infarction, or trauma.

• Papillary muscle dysfunction is usually caused by infarction.

• Other causes include the following:

• Ehlers-Danlos

• Marfan's

• Osteogenesis imperfecta

• Systemic lupus erythematosus (SLE)

• Chest x-ray (CXR)

• The cardiac silhouette is often normal in patients with mitral valve prolapse.

• With chronic mitral regurgitation, left ventricular and left atrial enlargement are present.

• The left atrium can be large enough that it produces elevation of the left mainstem bronchus.

• Occasionally, the double density sign can be seen along the right heart border, which is produced by the shadow of the wall of the dilated left atrium.

• The heart size of patients with CAD can range from normal to significant dilatation of the left ventricle and left atrium.

• Mitral regurgitation will present with acute pulmonary edema and a normal cardiac silhouette with acute mitral regurgitation that is secondary to a rupture of a valve apparatus.

• Two-dimensional echocardiography

• There will be evidence of posterior motion of valve leaflets during mid-systole in patients with mitral valve prolapse.

• Annular calcifications may be seen in patients with CAD. In addition, there can be evidence of posterior or inferior wall motion abnormalities.

• With acute mitral regurgitation, the ruptured chordae tendineae or papillary muscle, as well as perforated interventricular septum, can be visualized.

• The left atrium and ventricle will be of normal size.

• Transesophageal echo will provide a better estimate of the severity of damage.

Other Tests:

• Electrocardiogram (ECG)

• Chronic mitral regurgitation
• Atrial fibrillation is often present secondary to a dilated left atrium.
• The ECG will show evidence of left ventricular hypertrophy and left atrial enlargement.

• Coronary artery disease (CAD)
• There may be evidence of inferior and posterior Q waves, indicating prior infarction.

• Mitral valve prolapse (MVP)
• Patients most commonly will have ST and T wave changes, with T wave inversions in the inferior leads.
• It may reveal an underlying arrhythmia (eg, sinus arrhythmia, sinus arrest, atrial fibrillation, premature ventricular contractions [PVCs]).

• Acute mitral regurgitation
• May reveal evidence of an acute myocardial infarction, more commonly inferior or posterior.

Procedures:

• Cardiac catheterization

• Angiography is considered to be the gold standard in the assessment of the severity of the disease.

• It is graded on a scale from 0 (none); 1 (mild); 2 (moderate); 3 (moderately severe); and 4 (severe).

• The severity is based on the opacity of the left atrium.

• The regurgitant volume can be calculated based on information from the catheterization.

• In addition, this test will identify those with underlying CAD.

• Acute mitral regurgitation is a specific case in which immediate intervention in the ED can make a difference.

• If the etiology is myocardial infarction, infusion of thrombolytics may reestablish the blood flow to the papillary muscle, possibly restoring function.

• The mainstay of medical treatment in most other cases of mitral regurgitation is afterload reduction.

• Afterload reduction will decrease the impedance to left ventricular ejection and, as a result, decrease the regurgitant volume.

• The treatment of pulmonary edema should include oxygen, diuretics, nitrates, and early intubation if respiratory failure results.

• These individuals can benefit from afterload reduction with nitroprusside, even in the setting of a normal blood pressure.

• Do not attempt to alleviate tachycardia with beta-blockers. Mild-to-moderate tachycardia is beneficial in these patients because it allows less time for the heart to have backfill, which lowers regurgitant volume.

• Rapid atrial fibrillation secondary to chronic mitral regurgitation should be controlled with digoxin or diltiazem.

• The physician should consider cardioversion in refractory or unstable patients. If cardioversion is effective, however, the restored sinus rhythm is usually transient due to the left atrium being severely dilated.

Drug Name	Furosemide (Lasix)- An excellent preload reducer. Increases excretion of water by interfering with chloride-binding co-transport system which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until desired diuresis occurs. When treating infants, titrate with 1 mg/kg/dose increments until a satisfactory effect is achieved.
Adult Dose	1 mg/kg PO/IV; range of 20-120 mg
Pediatric Dose	2 mg/kg PO/IV
Contraindications	Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion
Interactions	Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Perform frequent serum electrolyte, CO2, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Drug Category: Nitrates - These agents are useful in preload reduction and as anti-anginal.

Drug Name	Nitroglycerin (Nitro-Bid)- Causes relaxation of the vascular smooth muscle via stimulation of intracellular, cyclic, guanosine monophosphate production, which causes a decrease in blood pressure.
Adult Dose	0.4 mg SL Spray: 1-2 sprays per dose Paste: 1-2 inches of paste q8h 50 mg in 250 cc D5W IV; start at 5 mcg/min and titrate until desired effect; not to exceed 200 mcg/min; watch for hypotension
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma closed angle glaucoma, or cerebral hemorrhage
Interactions	Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in coronary artery disease, and low systolic blood pressure

Drug Name	Nitroprusside (Nipride, Nitropress)- DOC for afterload reduction. Has an effect on afterload reduction, but also some effect on preload, produces vasodilation, and increases inotropic activity of the heart. In addition, reduces peripheral resistance by directly acting on arteriolar and venous smooth muscle.
Adult Dose	50 mg in 250 cc D5W; start at 3 mcg/kg/min up to 10 mcg/kg/min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; subaortic stenosis, idiopathic hypertrophic and atrial fibrillation or flutter
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may increase and can cause cyanide toxicity; sodium nitroprusside has the ability to lower blood pressure and thus should be used only in those patients with mean arterial pressures >70 mm Hg

Drug Category: Anti-arrhythmics - These agents are used for the control of atrial fibrillation in the setting of chronic mitral regurgitation.

Drug Name	Digoxin (Lanoxin)- DOC in rate-control of atrial fibrillation. Cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system.
Adult Dose	0.25 IV q6h up to 1 mg loading dose followed by a maintenance dose of 0.125-0.25 mg PO/IV qd
Pediatric Dose	Digitalization must be individualized
Contraindications	Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, and carotid sinus syndrome
Interactions	Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete A-V Block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis

Drug Name	Diltiazem (Cardizem)- Useful as second line of therapy in rate control of atrial fibrillation and chronic mitral regurgitation. During the depolarization, it inhibits the calcium ion from entering the slow channels or the voltage-sensitive areas of the vascular smooth muscle and myocardium.
Adult Dose	Bolus 0.25 mg/kg up to 20 mg IV over 2 min Rebolus with 25 mg or 0.35 mg/kg prn, then start infusion of 5-15 mg/h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe CHF, sick sinus syndrome, second- or third-degree AV block, and hypotension (< 90 mmHg systolic)
Interactions	May increase carbamazepine, digoxin, and cyclosporine, theophylline levels; when administered with amiodarone, may cause bradycardia and a decrease in cardiac output; when given with beta-blockers may increase cardiac depression; cimetidine may increase diltiazem levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur

• There are 2 primary surgeries: mitral valve replacement and mitral valve repair.

• If treated early enough, mitral valve repair is the optimal choice (ie, due to lower risk of infectious endocarditis and better postoperative left ventricular function).

• Repair is usually available only to those whose condition has a nonrheumatic, noninfectious, and nonischemic cause; therefore, there are few candidates for mitral valve repair .

• Valve replacement should not be undertaken in asymptomatic patients.

• Early recognition of even minimal symptoms is crucial in order to attempt to preserve as much left ventricular function as possible
• Chordal transection during replacement surgery will result in some impairment of left ventricle function; thus, the more left ventricular function prior to surgery, the better the outcome.

Complications:

• Patients with acute mitral regurgitation secondary to infarction emergently requiring valve replacement, have a 60-80% mortality if they present with severe pulmonary edema.

• Major complications from chronic regurgitation include:

• Severe LV dysfunction

• Chronic congestive heart failure

• Atrial fibrillation and its complications (eg, left atrial thrombus with embolization stroke)

• Sudden death, ruptured chordae tendinae, and endocarditis remain infrequent complications of regurgitation secondary to longstanding mitral prolapse.

Prognosis:

• The extent of left ventricular dysfunction from underlying ischemia is the primary prognostic determinant in those with regurgitation secondary to CAD.