Antihypertensive drugs are directed against a variety of pharmacological targets in various cell types in different organs involved in blood pressure control. The most important targets in the brain, heart, vasculature (vascular smooth muscle cells), and the kidney (nephron) are shown. Some diuretics produce some direct vasodilation; # non-ACE, conversion of angiotensin I (Ang I) to angiotensin II (Ang II) may occur independent from ACE due to the activity of other enzymes in different tissues such as chymase in the heart; DCT, distal convoluted tubule; CCT, cortical collecting duct; TAL, thick ascending limb of the loop of Henle; (-), indicates inhibition. Modified according to reference 3.

Algorithm for the treatment of hypertension

Algorithm for the treatment of hypertension

Unless contraindicated; based on randomized controlled trials;  Evidence suggests that the beneficial effects of ACE inhibitors can be duplicated with AT-1 antagonists (and probably vice versa). Thus, ACE inhibitors could be substituted by AT-1 antagonists in the case of troublesome side effects, such as cough under treatment with ACE inhibitors. Modified according to reference 5.

Effects of anticoagulants on the coagulation cascade

Coumarin (Warfarin) and the vitamin K cycle

Coumarin (Warfarin) and the vitamin K cycle

Abbreviations: glu, glutamate; gla, y-carboxyglutamate. (Modified from [2], with permission from Chest.)

Relative effects of UFH, LMWH, and fondaparinux on AT-mediated inhibition of factor Xa and thrombin (lla).

Relative effects of UFH, LMWH, and fondaparinux

AT-mediated inhibition of factor Xa and thrombin (lla). Whereas UFH catalyzes inhibition of Xa and thrombin equally well, only LMWH chains of 18 saccharide units or longer catalyze thrombin inhibition; thus, the anti-Xa/anti-lla ratio of LMWH preparations ranges from 2:1 to 4:1. In contrast, fondaparinux exclusively inhibits Xa. (Modified from [3], with permission from Chest.)

Desensitization, internalization and recycling of β-adrenergic receptors

Activation of β-adrenergic receptors causes their phosphorylation by members of the GRKs. Cytosolic β-arrestins then bind to the phosphorylated receptors and prevent further interaction with G-proteins. β-Arrestin-bound receptors assemble in clathrin-coated pits, where the complex appears to interact with other proteins, including dynamin and src-kinase. This leads (i) to the activation of non-conventional signalling pathways (raf-kinases, MAP-kinases, JNK-kinases), and (ii) to the internalization of the receptors to endosomes. Endosomal receptors become either dephosphorylated and recycle back to the cell surface; some endosomal receptors undergo lysosomal degradation.

β-Adrenergic signalling in cardiac muscle (predominantly β1) and smooth muscle (predominantly β₂) cells

β-Adrenergic signalling in cardiac muscle

β-Adrenergic signalling in cardiac muscle (predominantly β1) and smooth muscle (predominantly β₂) cells. Proteins that become more active after activation of β-adrenergic receptors are depicted in grey, those which become less active are depicted in white. Both receptors couple to G_s and lead to activation of adenylyl cyclases, generation of cyclic AMP and activation or protein kinase A (protein kinase A). In heart muscle cells, protein kinase A causes phosphorylation of L-type calcium channels (increased Ca²⁺-influx; relevant site of phosphorylation uncertain), troponin I (Tnl; diminishes affinity of troponin C for Ca²⁺ and thus enhances relaxation) and phospholamban (PLB; leads to less inhibition of the sarcoplasmic Ca²⁺ ATPase, SERCA, which pumps Ca²⁺into the sarcoplasmic stores. This in turn enhances relaxation and enhances Ca²⁺-release during the next beat) All this leads to more rapid and forceful contraction as well as relaxation. In smooth muscle cell the signalling pathways are less clear protein kinase A-mediated phosphorylation of myosin light chain kinase (MLCK) causes reduced activity of this kinase, which in turn leads to decreased phosphorylation of myosin light chains and, hence, reduced contraction. A second postulated mechanism for relaxation is hyperpolarization via activation of K⁺-channels; the signalling pathway is unclear and might involve coupling of β₂-receptors to G1.

Synthesis and release of noradrenaline and adrenaline

Noradrenaline and adrenaline are synthesized from the precursor amino acid tyrosine and are stored at high concentrations in synaptic vesicles. Upon activation of sympathetic nerves or adrenal chromaffin cells, noradrenaline and adrenaline are secreted and can activate adrenergic receptors on surrounding cells (sympathetic nerve), or they enter the blood circulation (adrenaline released from the adrenal gland). Release of noradrenaline from nerve terminals is controlled by presynaptic inhibitory α₂- and activating β₂-adrenergic receptors. Actions of noradrenaline are terminated by uptake into nerve terminals and synaptic vesicles by active transporters (NET, EMT, VMAT) and by uptake into neighboring cells (not shown). Abbreviations: AADC, aromatic L-amino acid decarboxylase; COMT, catechol O-methyltransferase; D(3H, dopamine β-hydroxylase; EMT, extraneuronal noradrenaline transporter; MAO, monoamine oxidase; NET, noradrenaline transporter; PNMT, phenylethanolamine-A/-methyltransferase; TH, tyrosine hydroxylase; VMAT, vesicular monoamine transporter.

Subtypes of a-adrenergic receptors, their signaling pathways and agonist and antagonist binding profiles.

Subtypes of α-adrenergic receptors

The proposed topology of a₁ and a₂-adrenergic receptors with 7 transmembrane domains is illustrated. Adrenaline and noradrenaline can also activate β-adrenergic receptors. PLA₂, PLC: phospholipases A, C; GIRK: G-protein-activated inwardly rectifying potassium channel, MAPK: mitogen-activated protein kinase.

Model of agonist and antagonist binding to α1-adrenergic receptors

Model of agonist and antagonist binding to α1-adrenergic receptors

Model of agonist and antagonist binding to α1-adrenergic receptors. The binding pocket of a1-receptors is depicted from an extracellular viewpoint, transmembrane domains 1-7 are numbered. Amino acids involved in agonist binding and receptor activation are depicted in blue, residues which mediate antagonist binding are shown in red (modified from 5).

A Kinase Anchoring Proteins (AKAPs)

A Kinase Anchoring Proteins. Model of an A kinase anchoring protein. The unifying characteristic of  A kinase anchoring proteins is the presence of a structurally conserved binding domain for the dimer of regulatory (R) subunits of PKA (RBD, regulatory subunit binding domain). In the inactive state, PKA forms a tetramer consisting of a dimer of R subunits each bound to one catalytic subunit (C). Binding of two molecules of cAMP to each R subunit causes a conformational change and release of the C subunits, which in the free form phosphorylate substrate proteins in close proximity. The RBD in all  A kinase anchoring proteins with pericentrin as the only exception forms an amphipathic helix that docks into a hydrophobic pocket formed by the dimerization and docking domain of R subunits. The targeting domain, which tethers the  A kinase anchoring protein complex to cellular compartments and docking domains, which bind further signalling proteins (e.g. phosphodiesterases, phosphatases or other kinases) are specific for individual  A kinase anchoring proteins. A few A kinase anchoring proteins possess catalytic activity such as the RhoGEF-activity in  A kinase anchoring protein-Lbc conferred by a DH domain. The proteins within the A kinase anchoring protein family are without obvious sequence homology.

β-adrenoceptor depend on AKAP–PKA

β-adrenoceptor-induced increases in cardiac myocyte contractility depend on A kinase anchoring protein-protein kinase A interactions. Stimulation of β-adrenoceptors (β1AR) on the surface of cardiac myocytes by binding of adrenergic agonists such as norepinephrine, epinephrine or isoproterenol increases contractility of the heart. Agonist binding to the receptors activates the G protein G_s and adenylyl cyclase, and consequent synthesis of cAMP which binds to regulatory (R) subunits of protein kinase A inducing dissociation of catalytic (C) subunits. The C subunits phosphorylate L-type Ca²⁺ channels located in the plasma membrane (plasmalemma) and ryanodine receptors (RyR2) embedded in the membrane of the sarcoplasmic reticulum (SR). Phosphorylation of the two channel proteins increases their open probability and leads to an increase in cytosolic Ca²⁺ causing increased contractility. Forthe relaxation of cardiac myocytes, Ca²⁺ has to be removed from the cytosol. A pivotal role in this plays sarcoplasmic Ca²⁺ ATPase (SERCA). It pumps Ca²⁺ back into the SR. SERCA is inhibited when bound to phospholamban (PLB) and activated upon dissociation from PLB, which is induced by P-adrenoceptor-mediated protein kinase A phosphorylation. Collectively, the protein kinase A phosphorylation events increase cardiac myocyte contractility. The efficient phosphorylation of L-type Ca²⁺ channels occurs only if protein kinase A is anchored to the channel by AKAP18a. For the phosphorylation of RyR, protein kinase A anchoring to this channel by mAKAP is a prerequisite. Further A kinase anchoring proteins are likely to be involved in protein kinase A-dependent phosphorylation events in response to P-adrenoceptor stimulation (e.g. PLB).

Right ventricular enlargement/ dysfunction and failure caused by pulmonary hypertension (increased right ventricular afterload) secondary to diseases of the lung, thorax, and pulmonary vasculature.

• Acute cor pulmonale: acute dilatation or overload of the right ventricle secondary to massive pulmonary embolism

• Chronic cor pulmonale: hypertrophy and dilatation of the right ventricle resulting from diseases of the pulmonary parenchyma and/or pulmonary vasculature (most commonly COPD)

System(s) affected: Cardiovascular, Pulmonary,
Renal/Uroiogic

Genetics: No known genetic pattern

Incidence/Prevalence in USA: 5-10% of adult
heart diseases

Predominant age: >45

Predominant sex: Male > Female

Medical Symptoms and Signs of Disease

• Acute cor pulmonale

– Severe dyspnea

– Pallor

– Diaphoresis

– Jugular venous distention with inspiration (Kussmaul’s sign)

– Systolic murmur loudest at left sternal border (tricuspid regurgitation)

– Distended, tender, pulsatile liver

– S3 gallop

– Hypoxemia

– Cardiovascular collapse because of right ventricle’s low output state

• Chronic cor pulmonale:

– Tachypnea/shortness of breath not relieved by sitting upright

– Hoarseness secondary to compression of the left recurrent laryngeal nerve by enlarged pulmonary vessels (Ortner syndrome)

– Productive or nonproductive cough

– Chest pain secondary to pulmonary artery root dilatation and right ventricular ischemia

– Hepatomegaly

– Peripheral edema

– Cyanosis

– Right ventricular systolic heave

– Pulmonary ejection click

– S3 gallop that increases with inspiration

– Jugular venous distention with prominent a- and v-waves

– Systolic murmur of tricuspid regurgitation

– Diastolic murmur of pulmonary regurgitation

– Right ventricular failure (indicated by increased venous pressure, edema, hepatojugular reflux, worsening tricuspid regurgitation, right ventricular pulsus alternans, development of S3 and S4).

What Causes Disease?

• Disease affecting pulmonary air spaces

– Diffuse interstitial lung diseases: idiopathic pulmonary fibrosis, radiation induced fibrosis

– Pulmonary resection

– Chronic obstructive pulmonary diseases (chronic bronchitis, emphysema, asthma)

– Granulomatous and connective tissue diseases: sarcoidosis, rheumatoid arthritis, systemic lupus erythematosus, eosinophilic granuloma, mixed connective tissue disease

– Bronchiectasis

– Cystic fibrosis

– Malignant infiltration

– Chronic hypoxia at high altitude

– Congenital structural defects

• Diseases affecting the pulmonary vasculature

– Primary pulmonary hypertension

– Pulmonary embolism

– CREST

– Tumor embolism

– Amniotic fluid embolism

– Schistosomiasis

– Sickle cell disease

– Pulmonary vascular disease secondary to systemic illness

– Human immunodeficiency virus

– Granulomatous pulmonary arteritis

– Chronic liver disease

– Intravenous drug abuse

• Diseases affecting thoracic cage function

– Obesity

– Kyphoscoliosis

Oneuromuscular diseases

– Sleep apnea

– Pleural fibrosis

– Idiopathic hypoventilation

• Pharmacologic induction

– Appetite suppressants, including aminorex, fenflura-mine, dexfenfluramine

Risk Factors

• Tobacco abuse

• Living at high altitudes

• Industrial exposures

Diagnosis of Disease

Differential Diagnosis

• Primary disease of the left side of the heart

• Congenital heart disease with left-to-right shunting

• Pulmonary arterial dissection

Laboratory

• Acute cor pulmonale: ventilation/perfusion mismatch with hypoxia and hypocarbia

• Chronic cor pulmonale: pulmonary function testing shows airflow obstruction with reduced p02 and possibly elevated hematocrit

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

• Evidence of underlying etiology

• Dilated, hypertrophic right ventricle

Special Tests

ECG: often normal, but findings can include:

• RVH: most common in primary pulmonary hypertension. Indicated by clockwise rotation of electrical axis, right axis deviation, and P pulmonale (increased P wave amplitude in II, III, and AVF)

• Right-sided heart failure suggested by: OR/S in V1>1

– R/S in V6<1 OR wave in V1>5mm

– P wave in ll>2.5 mm, consistent with right atrial enlargement

• Transient changes with hypoxia (arterial 02 saturation <85% and mean pulmonary arterial pressure >25 mm Hg) which may include:

– Rightward mean QRS axis (shift of 30° or more from former position)

– Biphasic, flattened, or inverted T waves in the precordial leads 0ST segment depression in II, III andaVF

– Incomplete or complete (rare) right bundle-branch block

Imaging

• Chest x-ray:

– Heart size may be normal in mild to moderate disease

– There may be counter-clockwise cardiac rotation and loss of aortic knob prominence with severe disease

In the PA view, the left heart border is mostly comprised of the right ventricle

– Pulmonary hypertension gives rise to dilatation of the pulmonary trunk and hilar vessels

• Echocardiography estimates right ventricular dimensions, right atrial pressure, systolic pulmonary artery pressure, and the severity of tricuspid regurgitation. In patients with chronic cor pulmonale secondary to COPD, there may also be late diastolic LV filling secondary to RV pressure/volume overload-induced structural distortion of the left ventricle.

• Thallium-201 myocardial scintigraphy and MRI can be used to diagnose right ventricular hypertrophy

• MRI can be used more specifically to characterize right ventricular ejection fraction and ventricular volume, including end-systolic and end-diastolic wall sizes

• CT angiography — aid in diagnosis of pulmonary arterial dissection

Diagnostic Procedures

• Right heart catheterization for quantitation of ventricular and pulmonary pressures and exclusion of congenital heart disease as etiology of right heart failure. Lung biopsy also helpful in discriminating among granulomatous and collagen-vascular diseases.

Treatment (Medical Therapy)

Appropriate Health Care

• Acute cor pulmonale: ICU setting

• Chronic cor pulmonale: outpatient

General Measures

• Vigorous antibiotic treatment of acute respiratory tract infections

• Avoidance of airway irritants (eg, tobacco smoke), sedatives and tranquilizers

• Treatment of underlying pulmonary disease, for example:

– Chronic obstructive pulmonary disease

• Bronchodilators to relieve obstruction

• Supplemental oxygen to correct hypoxia and acidemia

• Vasodilators, diuretics and phlebotomy (when HCT 55-60%) are possibly useful

– Digoxin with concomitant left ventricular failure

– Ventilatory abnormalities, eg, sleep apnea

• CPAP (continuous positive airway pressure) or BiPAP (biphasic positive airway pressure)

• Progestins

– Tracheostomy

• Acute or chronic thromboembolic disease

– Appropriate anticoagulation and hemodynamic support

Activity

As tolerated

Diet

Moderate salt restriction

Patient Education

• Signs of COPD exacerbation

• Sudden unilateral swelling of lower extremity in patient with hypercoagulability

• Diet restrictions

• Signs of edema to watch for

• Stress the need for adequate rest

• Referral to social service agency for home care help (oxygen, suctioning, etc)

• Report any signs of infections to physician

• Avoid use of nonprescription medications, especially sedatives

Medications (Drugs, Medicines)

Drug(s) of Choice

• Oxygen: Maintain arterial oxygen over 60 mm Hg (>8.0 kPa), if possible, to reduce pulmonary vascular resistance and improve myocardial dynamics. Excess oxygen depresses respiratory drive in patients with carbon dioxide retention.

• Theophylline: Bronchodilator, increases right ventricular ejection fraction (RVEF), and decreases pulmonary and systemic vascular resistance.

• Beta-adrenergic agonists: During acute, short-term administration, terbutaline beneficial probably by increasing RVEF and lowering pulmonary vascular resistance.

• Bronchodilators: (e.g., ipratropium, metaproterenol, albuterol) used every six hours and more often if necessary in order to maintain airway patency and arterial oxygen saturation

• Diuretics: (e.g., furosemide) for the relief of peripheral edema, combinations of furosemide and spironolactone (Aldactone) for ascites.

• Vasodilators: (e.g., hydralazine, nifedipine, diltiazem. prazosin) may be tried if conventional measures (oxygen and bronchodilators) fail. Success with these agents can only be accurately assessed with invasive monitoring. Benefit is obtained if the following criteria are met:

– Pulmonary vascular resistance reduced by 20%

– Cardiac output increases or remains unchanged

– Pulmonary artery pressure decreases or remains unchanged

– Systemic vascular resistance does not drop significantly. Consistent with the latter, monitor for systemic hypotension during initiation of therapy.

• In patients with primary pulmonary hypertension, calcium channel blockers (diltiazem, nifedipine) are a therapeutic mainstay as long as left ventricular dysfunction is not exacerbated. Patients at high-risk for thromboembolic phenomena should be anticoagulated with warfarin. Warfarin provides symptomatic improvement and decreases mortality in patients with primary pulmonary hypertension.

• Preliminary data with oral sildenafil shows it is an effective and selective pulmonary vasodilator that increases cardiac output without increasing wedge pressure in patients with pulmonary hypertension. Additional studies will be needed to determine the drug’s effect on outcomes in these patients.

• In patients with pulmonary arterial hypertension and WHO class III or IV symptom severity, bosentan (Tra-cleer) administered at 125mg po bid has been shown to improve exertional tolerance and walking distance. Tra-cleer has also been shown to improve cardiac function and reduce pulmonary vascular resistance, pulmonary arterial pressure, and mean right atrial pressure. Tra-cleer is an endothelin-1 receptor antagonist. Liver function tests must be monitored while patients are on this medication as it has been associated with liver toxicity. If ALT or AST levels exceed three times the upper limit of normal on therapy, it must be discontinued. The use of Tracleer is absolutely contraindicated in pregnant patients because of the high likelihood of inducing teratogenic effects.

Contraindications: Avoid sedatives and respiratory depressants

Precautions: Diuretics — monitor electrolytes as excessive loss of potassium and chloride may result in metabolic alkalosis, further impairing respiratory drive.

Significant possible interactions: Refer to manufacturer’s literature

Alternative Drugs

• Digoxin: Controversial; increases right heart contractility, but also induces pulmonary vasoconstriction, which may exacerbate right heart failure. Digoxin should be used in patients with cor pulmonale and concomitant left ventricular failure. Because of hypoxia and diuretic use, dangerous arrhythmias may develop.

• Other therapies being tested: inhalational nitric oxide, intravenous epoprostenol, and endothelin receptor blockers

Patient Monitoring

• Dependent on severity of underlying disease(s), extent of right heart failure, and medications in use

• Appropriate patients with advancing disease should be referred to centers specializing in lung and heart-lung transplantation. Right ventricular geometry and function tends to normalize subsequent to lung transplantation.

Prevention / Avoidance

Discontinue tobacco use, limit exposure to inhalational irritants and allergens

Possible Complications

N/A

Expected Course / Prognosis

• Depends on underlying disease and degree of pulmonary hypertension. 50,000 deaths per year in US from acute pulmonary embolism. In more chronic forms of cor pulmonale, there is a 10-50% 5 year mortality which improves with supplemental oxygen. In COPD with cor pulmonale, 3 year mortality is 60%.

• S1S2S3 on EKG, alveolar-arterial gradient >48 mm Hg during oxygen therapy, and right atrial overload indicate a poor prognosis when chronic cor pulmonale is secondary to COPD

Miscellaneous

Associated Conditions

• Left heart failure

Age-Related Factors

Pediatric: N/A

Geriatric: Metabolism of sedatives and narcotics slowed, thus the respiratory drive of these patients may be affected for prolonged periods

Pregnancy

Increased demand for placental pertusion may be severe

International Classification of Diseases

416.9 Chronic pulmonary heart disease, unspecified 415.0 Acute cor pulmonale

See Also

Congestive heart failure

Cystic fibrosis – besity

Alveolar proteinosis of the lung

Congestive heart failure (CHF) is the principal complication of heart disease. It is a pathophysiologic state produced by an abnormality in cardiac pump function (either transient or prolonged). The heart is unable to transport blood in a sufficient flow to meet metabolic needs. CHF occurs at some time in most cases of severe heart disease.

• This produces a variety of clinical circumstances from acute left ventricular dysfunction (due to tachyarrhyth-mia, bradyarrhythmia, and acute myocardial infarction) to chronic left ventricular dysfunction (due to chronic volume/pressure overload as seen in valvular heart disease)

• Two physiologic components explain most of the clinical findings of CHF — most patients have findings consistent with both mechanisms:

– an inotropic abnormality resulting in diminished systolic emptying (systolic failure)

– a compliance abnormality in which the ability of the ventricles to accept blood is impaired (diastolic dysfunction).

System(s) affected: Cardiovascular, Pulmonary

Genetics: N/A

Incidence/Prevalence in USA: Most common inpatient diagnosis for patients over 65

Predominant age: Varies by etiology of heart disease

Predominant sex:

• Male > Female — ages 40-75

• Male = Female — ages 75 and over

Medical Symptoms and Signs of Disease

• Early and mild impairment:

– Dyspnea on exertion-cardinal sign of left heart failure

– Deteriorating exercise capacity

– Easy fatigue

– Difficulty breathing

– Weakness

– Tachypnea with mild exertion

– Basilar rales

– Positive hepatojugular reflux

– Faint S3 gallop

– Nocturia

• Moderate impairment:

– Nocturnal nonproductive cough

– Orthopnea

– Paroxysmal nocturnal dyspnea

– Wheezing, especially nocturnal in absence of history of asthma or infection (cardiac asthma)

– Anorexia

– Fullness or dull pain in RUQ

– Tachypnea at rest

– Anxiety

– Hepatomegaly with tenderness to palpation

– Cool extremities due to peripheral vasoconstriction

– Prominent rales over bases

– Right pleural effusion

– Edema

– Gallop rhythm

– Diastolic hypertension

– Elevated jugular venous pressure

– Cardiomegaly

• Severe impairment:

– Cerebral dysfunction

– Abdominal bloating (ascites)

– Cyanosis

– Hypotension

– Puisus alternans

– Anasarca

– Frothy and/or pink sputum

– Increased P2

– Cardiac cachexia

– Cheyne-Stokes respirations

What Causes Disease?

• Coronary artery disease

• Myocardial infarction

• Cardiomyopathy

– Alcoholic

– Viral

– Long-standing hypertension

– Drugs (e.g., chemotherapeutic agents)

– Muscular dystrophy

– Amyloidosis

– Postpartum state

• Valvular abnormalities

– Aortic stenosis or regurgitation

– Rheumatic heart disease (mitral and aortic valvular disease)

• Renal artery stenosis, usually bilateral, may cause recurrent “flash” pulmonary edema

• Volume overload

• Cardiac depressants; negative inotropes (e.g., beta blockers, IV amiodarone)

• Arrhythmias, eg, atrial fibrillation

• High output states

– Hyperthyroidism

– Beriberi heart disease

• HIV

Risk Factors

• latrogenic reduction of intensity of therapy

• Inappropriate sodium and/or fluid excess

• Patient non-compliance

• Intercurrent arrhythmia, eg, atrial fibrillation

• Administration of drug with negative inotropic effects

• Excessive physical, emotional, or environmental stress

• Thyrotoxicosis, pregnancy, or any condition associated with increased metabolic demand

• Recent pregnancy (postpartum cardiomyopathy)

Diagnosis of Disease

Differential Diagnosis

• Simple dependent edema

• Exertional asthma

• Severe diffuse CAD

• Occult COPD

• Nephrotic syndrome: excluded by absence of history of asymptomatic edema, proteinuria in nephrotic range, and history of renal disease

• Cirrhosis: excluded by absence of stigmata of liver disease, and history of liver disease and its risk factors

• Left heart failure: findings of pulmonary congestion and diminished cardiac output appearing in patients with myocardial infarction, aortic and mitral valve disease, and hypertensive disease

• Right heart failure: findings of systemic vascular congestion (edema, ascites) appear in patients with cor pulmonale, tricuspid insufficiency, and most commonly in patients with uncorrected prolonged left heart failure

• Venous occlusive disease with subsequent peripheral edema

Laboratory

• B-type natriuretic peptide (BNP) is a marker of ventricular dysfunction; >100 is consistent with CHF. May be helpful in:

– Evaluating treatment since its value changes rapidly

– The emergency setting to help differentiate the cause of dyspnea

• Lab findings in early and mild to moderately severe CHF

– Respiratory alkalosis

– Mild azotemia

– Decreased erythrocyte sedimentation rate

– Proteinuria (usually less than 1 gm/24 h that clears with treatment)

• Lab findings in severe CHF

– Increased creatinine

– Hyperbilirubinemia in severe cases

– Dilutional hyponatremia

Drugs that may alter lab results: N/A

Disorders that may alter lab results: Renal failure may elevate BNP

Pathological Findings

• Early and acute

– Firm lungs with microscopic revealing engorged capillaries with thickening of the alveolar septa with extravasation of red cells and edema fluid

– Liver is engorged, firm, and fluid-filled. Microscopic — reveals dilated central hepatic veins and sinusoids.

• Late and chronic

– Hemosiderin deposits in lungs

– “Nutmeg” liver with centrilobular necrosis

– Occasionally hemorrhagic nonbacterial enterocolitis with hemorrhagic necrosis secondary to mesenteric vasoconstriction

Imaging

• X-ray — mild changes: pulmonary artery wedge pressure = 18-23 mm Hg (2.4-3.1 kPa)

– Increased heart size 01 ncreased blood flow to the upper lobes

– Equalization of flow between the upper and lower lobes

• X-ray — moderate severe pulmonary artery wedge pressure = 20-25 mm Hg (2.7-3.3 kPa)

– Interstitial edema

– Kerley’s B lines

– Perivascular edema

– Subpleural effusions

• X-ray — severe changes: pulmonary artery wedge pressure > 25 mm Hg (> 3.3 kPa)

– Alveolar edema

– Butterfly pattern of pulmonary edema

Diagnostic Procedures

• Echocardiographic studies are the most useful tests

• Cardiac catheterization, both right and left, for full diagnosis and prognosis

• B-type natriuretic peptide (BNP) is a useful marker of ventricular dysfunction. It is a cardiac neuro-hormone secreted from the ventricles in an increasing amount in response to abnormal pressure overload and increasing volume. The levels of BNP have been shown to increase in patients in correlation with progressive worsening of NYHA class of congestive heart failure (CHF). B-type natriuretic peptide has been shown to better predict the presence or absence of CHF than any set of clinical or lab measures of the cause of dyspnea. A level of over 100 is consistent with CHF. The level changes rapidly in response to treatment or worsening of the situation, so may be helpful not only in diagnosis but in following the benefit of treatment. It is helpful in the emergency room to differentiate the cause of dyspnea.

• Complete PFTs

• Nuclear imaging to evaluate LVand RVsize and systolic function

Treatment (Medical Therapy)

Appropriate Health Care

Inpatient when severe

General Measures

• Immediate treatment of the heart failure

• Search for underlying correctable conditions

• Eliminate contributing factors when possible

• Supplemental oxygen

• Antiembolism stockings

• Fluid and sodium restriction. Education about this is imperative for long term control. Daily weights guide overall therapy.

• Identify and control underlying correctable conditions (e.g., acute Ml, valvular disease, hyperthyroidism, but most commonly inadvertent salt and/or fluid overload)

Surgical Measures

• Heart valve surgery — possibly, if defective heart valve is responsible; mitral valve repair especially helpful if mitral regurgitation is aggravating CHF

• Cardiac transplantation — to be considered in patients (age < 55) without other disqualifying medical problems, who are developing CHF unresponsive to other therapeutic maneuvers, and who are felt to have a life expectancy of less than a year

• Biventricular pacing

Activity

• During severe stage, bed rest with elevation of head of bed and anti-embolism stockings to help control leg edema

• Gradual increase in activity with walking will help increase strength

Diet

• Sodium restriction (initially 4 gm sodium qd)

• Weight reduction diet if appropriate

• Low fat diet to retard coronary artery disease

• Appropriate fluid restriction

Patient Education

• Printed patient information available from:

– American Heart Association, 7320 Greenville Avenue, Dallas, TX 75231, (214)373-6300

– American College of Cardiology, 911 Old Georgetown Road, Bethesda, MD 20814, (301) 897-5400

Medications (Drugs, Medicines)

Drug(s) of Choice

• Diuretics, usually in combination with digitalis are used to initiate therapy. ACE inhibitors have become a mainstay of therapy. For acute pulmonary edema, IV morphine remains cornerstone of therapy.

• Digoxin

– Improves contractility, slows ventricular rate in atrial fibrillation

– May be harmful in acute Ml, hypertrophic cardiomy-opathy, or aortic stenosis

– Loading dose should be sufficient to have early beneficial effect, especially in atrial fibrillation with a rapid rate, e.g., 0.5-1.0 mg IV/PO, then another 1.0-1.5 mg in divided doses q4-6h

• Diuretics

– Furosemide (Lasix): IVorPO, depending on severity of pulmonary congestion. May require continuous drip.

– Metolazone (Zaroxolyn): excellent addition when furosemide does not seem to be sufficient

– Spironolactone: when used carefully, to avoid hyperkalemia. An important addition to difficult chronic cases.

• ACE Inhibitors

– Used to decrease afterload — shown to increase survival

– Improve general symptomatology and overall exercise capacity

• Beta-blockers

– Carvedilol (Coreg) 3.125 mg po bid for 2 weeks, then 6.25 mg bid for 2 weeks, increased to maximum 25 mg bid for class I to III CHF

– Bisoprolol (Zebeta) 5-20 mg/day: in CIBIS-II study significantly decreases all-cause mortality and sudden death (“treatment effects were independent of the severity or cause of heart failure”)

• Vasodilators

IV nitroglycerin may be of short-term benefit to decrease preload, afterload, and systemic resistance.

– Oral medications, e.g., hydralazine, prazosin, and Isosorbide dinitrate demonstrate tachyphylaxis

Contraindications: Refer to manufacturer’s literature

Precautions: ACE inhibitors may produce hypotension on first use in volume depleted patients. Beta-blockers may produce profound hypotension.

Significant possible interactions: Calcium channel blockers may impair LV function especially when used with beta blockers. Amiodipine seems less likely to be a problem.

Alternative Drugs

• Sympathomimetic amines. Can be used in severe CHF unresponsive to above measures

– Dopamine and dobutamine have been successful for short periods in treatment

– Dobutamine can be used on an intermittent outpatient basis with intermittent infusion. However in spite of possibly improving quality of life, reduces long-term survival.

Patient Monitoring

• Variable depending on clinical circumstances. Initially every 2-3 weeks after patient stabilized.

• Closely follow — history and physical findings, chest x-ray, electrolytes, BUN, and creatinine

Prevention / Avoidance

Treatment of underlying disorders when possible

Possible Complications

• Electrolyte disturbance

• Atrial and ventricular arrhythmias

• Mesenteric insufficiency

• Protein enteropathy

• Digitalis intoxication

Expected Course / Prognosis

• Result of initial treatment is usually good, whatever the cause

• Long-term prognosis variable. Mortality rates range from 10% with mild symptoms to 50% with advanced, progressive symptoms.

Killip classification for heart failure
Class Interpretation Mortality rate
I No CHE <5« II Mild-Moderate CHFt 10% III Severe CHFtt 30% IV Cardiogenic shockttt >80«
bibasilar rales and/or S3 gallop tt rales over > 50% lung fields, S3 gallop, pulmonary edema ttt BP <90 mm Hg «12 kPa) with hypo-perfusion, e.g., oliguria, confusion, clammy skin

Miscellaneous

Associated Conditions

See Causes

Age-Related Factors

Pediatric: Usually associated with congenital heart

Geriatric:

• Medications may need dosage adjustment

• Age-related cardiomyopathy is an increasing problem. It should be considered when the elderly complain of unusual dyspnea or easy fatigue. Beta-blockers may be of help.

Pregnancy

If occurs, will require special care

Synonyms

• Heart failure

• Dropsy

• Circulatory failure

• Cardiac failure

International Classification of Diseases

428.0 Congestive heart failure, unspecified

See Also

Abbreviations

CCF = congestive cardiac failure

The central atrioventricular (AV) portion of the cardiac septum and the contiguous mitral and tricuspid valves are abnormal, allowing for an unobstructed atrioventricular canal. Children with Down syndrome and this anomaly rapidly progress to pulmonary vascular obstructive disease (within 3 to 6 months).

• Rastelli classification:

– Type A: Common anterior AV valve leaflet is divided and attached to the crest of the ventricular septum by chordae

– Type B: Common anterior AV valve leaflet is divided and chordae tendineae from the midportions of the divided anterior leaflet are attached to the right ventricular medial papillary muscle

– Type C: Common anterior AV valve leaflet is undivided and not attached to the ventricular septum (free-floating leaflet)

System(s) affected: Cardiovascular

Genetics: No known genetic pattern

Incidence/Prevalence in USA: 1 in 250,000 live births; type A being the most common

Predominant age: Congenital, present at birth

Predominant sex: Female > Male

Medical Symptoms and Signs of Disease

• Pulmonary congestion

• Congestive heart failure

• Low systemic arterial blood oxygen saturation

• Tachycardia

• Poor feeding

• Growth failure

• Mitral regurgitation

• Pulmonary vascular obstructive disease, and cyanosis (30% in the first 2-3 years)

What Causes Disease?

Defective development of the endocardial cushions

Risk Factors

Unknown

Diagnosis of Disease

Differential Diagnosis

• Atrial septal defect

• Ventricular septal defect

• Incomplete or intermediate AV canal

• Patent ductus arteriosus

• Mitral valve prolapse

• Secondary mitral regurgitation

• Pulmonary vascular obstructive disease

• Anomalous pulmonary venous return

Laboratory

Arterial blood gas

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

Low oxygen saturation in the arterial blood gas

Special Tests

• Cardiac 2-D echo-Doppler showing anatomic defect, increased pulmonary pressures, mitral regurgitation, tricuspid regurgitation, right and left atrial and ventricular enlargements

• ECG — superior QRS axis, right ventricular hypertrophy (RVH), left ventricular hypertrophy (LVH), possibly peaked P waves

Imaging

• Cardiac angiogram demonstrating AV canal and mitral and tricuspid regurgitation, left and right atrial and ventricular enlargement

• Chest x-ray showing increased pulmonary vasculature. left and right atrial and ventricular enlargement

• MRI offers excellent imaging of crux

Diagnostic Procedures

• Pulmonary artery catheter showing prominent “V: waves, elevated pulmonary capillary wedge pressures, right atrial “step-up” in oxygen saturations

• Angiography

Treatment (Medical Therapy)

Appropriate Health Care

Medical management (digoxin, diuretics, afterload reducers) either as an inpatient or an outpatient, dependent upon the patient’s condition

General Measures

Provide general treatment for congestive heart failure

Surgical Measures

If pulmonary edema, growth failure and congestive heart failure is refractive in spite of optimal medical therapy, reparative surgery should be pursued as early as possible. Repair should be especially early in children with Down syndrome (approximately 3 months). Repair should be performed before 2 years of age to avoid the continued progression of pulmonary vascular obstructive disease. Patients more than 2 years of age can undergo repair if the pulmonary vascular resistance (PVR) does not exceed 8-10 units-meters squared. At a minimum, surgical correction includes closure of the interatrial and interventricular septal defects and suspension of the medial aspects of the left and right AV valve leaflets. Pulmonary artery banding might still be a possibility.

Activity

As tolerated

Diet

High calorie, low salt

Patient Education

Instruct regarding travel to altitudes and plane travel causing potential hypoxia

Medications (Drugs, Medicines)

Drug(s) of Choice

Digoxin, ACE inhibitors or isosorbide dinitrate plus hydralazine, furosemide; potassium supplementation

• Doses for term infants

– Digoxin -oral 30 /jg/kg (digitalizing), then 10/vg/ kg/24 hrs. Adjust to maintain levels within therapeutic range — 0.5-2.0 ng/mL (0.64-2.6 nmol/L)

– Captopril — 0.05-0.1 mg/kg/dose tid-qid

– Isosorbide dinitrate — refer to manufacturer’s literature

– Hydralazine — 0.75-3.0 mg/kg/dose, increase as needed to maximum of 6 mg/kg/dose

– Furosemide — oral 2 mg/kg, increase as needed to maximum of 6 mg/kg

– Potassium — supplement patients who require furosemide. Maintenance dose is 2-3 mEq/kg/24 hours.

Contraindications: Profound systemic hypotension, worsening hypoxia and V/Q mismatch with treatment

Precautions: Refer to manufacturer’s literature

Significant possible interactions: Refer to manufacturer’s literature

Alternative Drugs

Dobutamine or amrinone drips

Patient Monitoring

• As indicated by clinical intervention and disease progression

• Serial measurements of arterial oxygen content

• Serial measurements of pulmonary vascular resistance

Prevention / Avoidance

Avoid hypoxic embarrassment in environments of low oxygen tension

Possible Complications

• Refractive hypoxia secondary to progressive pulmonary vascular obstructive disease

• Cyanosis

• Polycythemia

• Growth failure

• Congestive heart failure/pulmonary edema

• Complications of surgery:

– Residual ventricular septal defect

– Residual left ventricular to right atrial shunting

– Complete AV block

Expected Course / Prognosis

• PVR less than 5:

– If undergoing reparative surgery, are at risk for an approximate 10% surgical mortality

– The majority of those surviving realize complete relief of their symptoms and will need no further treatment

• PVR between 5-13 undergoing surgery:

– Perioperative mortality approaches 33%

– Survivors realize functional class I or II (New York Heart Association [NYHA] classification)

• PVR greater than 5 who do not or can not undergo surgical intervention:

– Deterioration is progressive with death ranging from 2-16 years of age

Miscellaneous

Associated Conditions

• Down syndrome. Very high percentage have complete atrioventricular canal lesions.

• Tetralogy of Fallot

• Unbalanced canal with left or right dominance

Age-Related Factors

Pediatric: Surgical intervention before age 2 or before marked increase in PVR occurs

Geriatric: N/A

Pregnancy

N/A

International Classification of Diseases

745.69 Endocardial cushion defects, other

See Also

Atrial septal defect (ASD)

Abbreviations

AVC = atrioventricular canal

PVR = pulmonary vascular resistance

V/Q = ventilation-periusion ratio

A constriction (discrete or of varying lengths) of the aorta usually located just distal to the left subclavian artery at the junction of the ligamentum arteriosum

System(s) affected: Cardiovascular

Genetics: No Mendelian inheritance, but common in Turner syndrome

Incidence/Prevalence in USA: 64/100,000 under 1 year of age

Predominant age: Usually diagnosed in infancy

Predominant sex: Male> Female (1.7:1)

Medical Symptoms and Signs of Disease

• Headaches

• Exertional leg fatigue and pain

• Prominent neck pulsations

• Epistaxis

• Hypertension

• Pulse disparity: radial — femoral pulse delay and increased amplitude in brachial verses femoral pulse

• Fundoscopy: corkscrew tortuosity of retinal arterioles

• Delayed, weak, or absent pulse

• Prominent left ventricular impulse

• Murmur (aortic stenosis or insufficiency, ventricular septal defect, rarely mitral valve)

• S4 systolic ejection click

• Bruit (coarctation, collaterals, patent ductus arteriosus)

• Cyanosis, rarely

• In infancy may also have heart failure, failure to thrive, irritability, tachypnea, and dyspnea

• Extensive collaterals develop from branches of the subclavian, internal mammary, superior intercostal, and axillary arteries

What Causes Disease?

Congenital: Takayasu arteritis, Turner syndrome, multiple left-sided obstruction, Williams-Beuren syndrome

Risk Factors

• Turner syndrome

• Congenital left heart abnormalities

• Family history of left ventricular outflow tract obstruction

Diagnosis of Disease

Differential Diagnosis

• Takayasu arteritis

• Neurofibromatosis

• Pseudocoarctation (with or without hypertension, peripheral vascular disease)

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

• Segmental tubular hypoplasia

• Discrete obstruction with medial thickening

• Distal aneurysm

Special Tests

• Doppler examination of pulses reveals disparity

• Electrocardiogram may show left ventricular hypertrophy

• Blood pressures — all 4 extremities: upper limb systemic hypertension and differential of > 10mmHg

Imaging

• Chest x-ray may show rib notching, “3″ sign, rarely cardiomegaly

• Echocardiography for coarctation and coexisting cardiac anomalies

• Transesophageal echocardiography

• Magnetic resonance imaging (MRI)

Diagnostic Procedures

Cardiac catheterization and angiography: post-stenotic dilation

Treatment (Medical Therapy)

Appropriate Health Care

Inpatient surgery

General Measures

N/A

Surgical Measures

• Surgical correction or balloon angioplasty can be done in infancy if urgently needed. Best results when performed age 1 -2 years.

• Surgery should be done in childhood and adulthood as soon as coarctation diagnosed to prevent late complications

• Three common surgical procedures for correction of coarctation include (1) end-to-end anastomosis, (2) patch aortoplasty (insertion of Dacron patch), and, (3) subclavian flap procedure

• Balloon angioplasty of coarctation offers good results for primary treatment and for postoperative re-stenosis

• Stent placement

– May prevent unnecessary dilation of coarctation during angioplasty

– May further prevent late recoarctation than angioplasty alone

Activity

Exercise may exacerbate hypertension, but normal activity recommended after correction

Diet

No special diet

Patient Education

• Discuss post-coarctation syndrome

• For patient education materials favorably reviewed on this topic, contact: American Heart Association, 7320 Greenville Avenue, Dallas, TX 75231, (214)373-6300

Medications (Drugs, Medicines)

Drug(s) of Choice

• Alprostadil (prostaglandin E1), patency of ductus arteriosus

• Antibiotic prophylaxis (for dental and/or invasive procedures) for life (even after correction)

• Antihypertensives if needed

• Preload and afterload reduction if heart failure develops

Contraindications: Refer to manufacturer’s profile of each drug

Precautions:

• Lowering upper extremity blood pressure may cause hypoperfusion of lower extremities

• Lowering blood pressure not advised in pregnancy unless emergency

Significant possible interactions: Refer to manufacturer’s profile of each drug

Alternative Drugs

N/A

Patient Monitoring

Frequent postoperative followup for evidence of re-stenosis (check for hypertension and pulse disparities) and late complications

Prevention / Avoidance

Patients should be encouraged to have normal lifestyles and activities after coarctation correction

Possible Complications

• Most common with late or no correction

• Heart failure

• Aneurysm of circle of Willis, rupture possible

• Hypertension

• Rupture or dissection of aortic aneurysm

• Endarteritis or endocarditis (need antibiotic prophylaxis)

• Aortic valve disease (stenosis or insufficiency)

• Post coarctectomy syndrome: recurrence, hypertension, atherosclerotic heart disease, aneurysm at site of coarctectomy, progressive aortic stenosis and/or regurgitation

• Fistula formation between aorta and airways leading to hemoptysis

Expected Course / Prognosis

• Depends on age of repair and presence of other cardiac abnormalities

• Residual or restenosis (6-33%)

• Subsequent cardiac surgery (11%)

• Hypertension (25%)

• Survival after surgery: 10 years (91 %), 20 years (84%), 30 years (72%)

• Uncorrected, 80% mortality before age 50

Miscellaneous

Associated Conditions

• Bicuspid aortic valve (85%)

• Patent ductus arteriosus (65%)

• Ventricular septal defect (30-35%)

• Aortic stenosis and/or insufficiency

• Subvalvular aortic stenosis

• Mitral valve abnormalities (common)

• Transposition of great vessels or double outlet right ventricle

• Aneurysm of circle of Willis

• Neurofibromatosis

• Acquired intercostal aneurysms

Age-Related Factors

Greater risk of complications if correction is delayed beyond early childhood. Often diagnosis is delayed.

Pediatric: N/A

Geriatric: N/A

Pregnancy

Uncorrected (or restenosis) coarctation carries high risk of aortic rupture or dissection and cerebral hemorrhage (aneurysm of circle of Willis rupture), but lower risk of pre-eclampsia than other forms of hypertension

International Classification of Diseases

747.1 Coarctation of aorta

747.10 Coarctation of aorta (preductal) (postductal)

In carotid sinus syndrome (CSS), stimulation of one or both of the hypersensitive carotid sinuses at the bifurcation of the common carotid arteries produces brief episodes of faintness or loss of consciousness. Four types are described:

• Cardioinhibitoty: vagally mediated causing bradycardia, sinus arrest or atrioventricular block for > 3 seconds

• Vasodepressor: a sudden drop of peripheral vascular resistance leads to > 50 mm Hg decrease in systolic BP without change in heart rate, or to > 30 mm Hg symptomatic drop in systolic BP

• Mixed: combined cardioinhibitory and vasodepressor changes

• Cerebral: extremely rare, carotid sinus hypersensitivity occurs without bradycardia or hypotension

System(s) affected: Cardiovascular, Nervous

Genetics: N/A

Incidence/Prevalence in USA: up to 10% of the adult population, mostly after 50 years of age

Predominant age: Elderly

Predominant sex: Male > Female

Medical Symptoms and Signs of Disease

• Dizziness

• Syncope

• Falls

• Blurred vision

• Vertigo

• Tinnitus

• Bradycardia

• Hypotension

• Pallor

• Sweating

• Tachypnea

• No postictal symptoms

What Causes Disease?

• Idiopathic

• Stimulation of the hypersensitive baroreceptors in the carotid sinus affects vagus and sympathetic nerve outflow

• Carotid body tumors

• Inflammatory and malignant lymph nodes in the neck

• Metastatic cancer

• Coronary artery disease

Risk Factors

• Diffuse atherosclerosis

• Wearing tight collars

• Shaving over region of carotid sinus

• Emotional upheaval

• Head movement

Diagnosis of Disease

Differential Diagnosis

• Vasovagalsyncope

• Postural hypotension

• Primary autonomic insufficiency

• Hypovolemia

• Arrhythmias

• Sick sinus syndrome

• Syncope secondary to reduced cardiac output

• Cerebrovascular insufficiency

• Emotional disturbances

• Other causes of syncope

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

N/A

Special Tests

With the patient in the supine position and while the ECG is monitored, manual massage of the carotid sinus causes asystole of more than 3 seconds (cardioinhibitory) and/or a drop in systolic BP as described in Description.

Diagnostic Procedures

• Carotid sinus massage (check for potential contraindications before performing massage including carotid bruits, known carotid hypersensitivity, demonstrated carotid artery disease)

• Electrophysiologic studies

• Electrocardiogram

• Carotid duplex scan

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient. No treatment is required for asymptomatic individuals.

General Measures

Cardiac pacing (dual chamber) is the treatment of choice

Surgical Measures

• Carotid sinus denervation (CSD) by surgery or radiation therapy for selected patients

• Dual chamber pacemaker helps in preventing recurrent symptoms in patients with cardioinhibitory component

• Surgery for selected patients with atheromata

Activity

No restrictions

Diet

No special diet

Patient Education

Avoidance of exacerbating factors that might stimulate the carotid sinus — tight neck collar, shaving, turning of the head to one side, straining at stool

Medications (Drugs, Medicines)

Drug(s) of Choice

• Anticholinergics — atropine for the cardioinhibitory type

• Sympathomimetics — ephedrine

• Theophylline

• In one recent study, SSRIs were successful in controlling symptoms

Contraindications: Refer to manufacturer’s instructions

Precautions: Concomitant usage of digitalis, beta-blockers, clonidine and alpha-methyldopa may accentuate response to carotid sinus massage

Significant possible interactions: Refer to manufacturer’s instructions

Alternative Drugs

• Fludrocortisone has been used in clinical trials for patients with vasopressor CSS

Patient Monitoring

Follow as an outpatient

Prevention / Avoidance

• Avoidance of pressure on the neck

• Support hose may be helpful for some patients with vasodepressor type

Possible Complications

• Prolonged confusion

• Frequent falls leading to injuries and fractures

Expected Course / Prognosis

Serious if syncope associated with atheromatous narrowing of sinus artery or basilar artery

Miscellaneous

Associated Conditions

• Sick sinus syndrome

• Atrioventricular block

• Coronary artery disease

Age-Related Factors

Pediatric: N/A

Geriatric: More likely to occur in elderly. Should be considered in elderly patients with frequent falls.

Pregnancy

N/A

Synonyms

• Hypersensitive carotid sinus syndrome

• Carotid sinus syncope

• Carotid sinus hypersensitivity

International Classification of Diseases

337.0 Idiopathic peripheral autonomic neuropathy

See Also

Atherosclerosis

Other Notes

It is clinically important to distinguish CSS from sick sinus syndrome

Abbreviations

CSS = carotid sinus syndrome