NPLEX Combination Review Cardiovascular Part 1

Paul S. Anderson, ND Medical Board Review Services

Copyright MBRS

•

SGOT / AST “A sick heart can beat f-AST”

– Identify and monitor

HEART!!! ,

Kidney,hepatocellular damage – Increased in early MI (peak at 24-36 hrs.) •

SGPT / ALT “L is for Liver”

– Identify and monitor hepatocellular damage.

–

ALT>AST Mainly = Liver Dz.

•

GGT / GGTP

– Useful in detecting space-occupying lesions, biliary dysfunction and

ETOH abuse – Chemical toxicity.

•

CPK

– Most often performed to document an acute MI; should be performed upon admission to hospital (after 12 hours but before 24 hours).

– CPK-MB elevation also may be associated with pulmonary embolism.

• •

LDH (118.0 – 273IU/ml)

Principle measurement to diagnose conditions in which there is tissue damage.

Isoenzymes:

–

LDH-1 Normally Lower than LDH-2

– – – –

In MI: LDH-1>LDH-2!

Liver Dz: LDH< AST&ALT Pernicious Anemia LDH may be 50X Normal LDH 5 Increase in Muscle Dz’s LDH ELEVATIONS

– Acute MI – Myocarditis – Liver disease – Tissue necrosis – CHF – Shock – Pancreatitis – Acute renal infarction – Hemolysis – Skeletal muscle disease – Trauma – Multi-system disease – Collagen-vascular disease

–

Troponin-1Increase

–

CK / MB Increase

–

Myoglobin Increase

–

AST

–

LDH-1>LDH-2!

MI

2-4 hours post-MI 4-6 hours post 4-8 hours post 6- 36 hours post 12-48 hours post

Plasma Lipid Profile

Used to determine cardiac risk and to aid in the diagnosis of lipoprotein metabolism disorders: • Total cholesterol (< 200mg/dL) – HDL (< 35 mg/dL confer increased myocardial risk) – LDL (> 100mg/dL associated with increased myocardial risk) • Triglycerides (< 250mg/dL) • Apolipoprotein A1 (> 140mg/dL) Lipoprotein portion of HDL.(Higher = better) may be more useful than HDL cholesterol to identify patients with CAD • Apolipoprotein B (70 –110 mg/dL) major apoprotein of LDL and VLDL; elevated levels indicate increased myocardial risk • Lipoprotein (a) (< 30mg / dL) – Correlates CAD risk; concentrations > 30mg/dL correlate 2X greater risk of developing CAD. (<20 desirable range). Used in predicting stent closure post-surgery.

Plasma Lipid Profile

• Genotyping Hyperlipidemia Fredrickson’s Types:

– Sub Types I, II, III, IV (Definitive dx with lipid electrophoresis) – IV Most Common • •

Chol. = / > 200 HDL = Low / LDL = High

•

TG > Chol.

– II Second Most Common • •

Chol. > 200 TG Normal

• • • • • • •

Homocysteine

– Increased levels in serum may confer increased myocardial risk.

Ammonia (NH3) (5-50mmol/l)

– Severe liver disease is the most common cause of elevated levels.

Vitamin B12 (> 200pg/ml)

– Decreased values in

pernicious anemia

and alcoholism.

Folate (200 – 640ng/ml)

– DECREASED in

megaloblastic anemia

and alcoholism.

– INCREASED in acute renal failure and liver disease.

TIBC (% Transferrin saturation) 255

thalassemias.

hemochromatosis.

–450mcg/dL

– Usually performed in conjunction with serum iron in the evaluation and diagnosis of iron-deficiency anemia, chronic disease anemia and – INCREASED: Fe deficiency anemia, PG and OBC.

– DECREASED: Anemia chronic disease, sideroblastic anemia and

Calculating % Fe. Saturation Serum Iron:

– VERY labile! Changes quickly.

Serum Iron (mcg/dL) / TIBC (mcg/dL) Ferritin (20 – 300ng/ml)

– Detection of iron deficiency and anemia by reflecting storage of iron.

• • • • •

Vascular Studies

ARTERIAL

– AORTA: Performed when working-up probable aneurysms – CAROTID: Performed to ensure normal vascular anatomy of common carotid artery, internal and external carotids; ruling out stenos is or occlusion – LEA: Examining extremity arterial anatomy, normal triphasic blood flow, plaques or other pathological lesions and normal segmental blood pressure.

VENOUS

– LEV: Normal venous anatomy with spontaneous, phasic blood flow pattern, normal venous augmentation with no pathological valves present.

Advantages

– Noninvasive without radiation risk.

– May obviate need for costly hospitalization.

– Structural image therefore useful for patients with organ function dysfunction.

– Does not require ingestion of contrast dyes.

Disadvantages

– Requires skilled technician to operate transducer.

– Air-filled structures cannot be studied with this procedure.

– Obese & restless patients cannot be adequately studied.

Interfering factors

– Bowel gas (air) complicates procedure.

– No open wound or dressing can be used to visualize deep structures.

Electrocardiogram

• • •

Resting ECG

– Performed to establish baseline ECG.

Stress / exercise ECG

– Graded exercise tolerance test. Systolic values usually increase. Diastolic usually remains unchanged.

– Test measures the efficiency of the heart during a dynamic exercise stress period.

– Valuable for diagnosing IHD, underlying pathophysiological functioning.

Holter monitor

– Method of continuously recording the ECG; often for 24 hours.

– Provides documentation of suspected cardiac rhythm disturbances.

ECG Findings

• Infarction – Pathologic Q-Waves • .04 sec or > & 1/3 as deep as R-Wave is high (all but AVR) – S-T Segment changes • Tall T’s, (S-T elevations) – Age of infarct • Hyperacute: Normal Q, ST Elevation, upright T • Acute: Q MB Pathologic, ST Less Elevated, T inverted • Recent: Q-Change, Isoelectric S-T, Symmetrical T inv.

• Old: Significant Q- changes, Isoelectric T waves • Drug / Electrolyte changes – Digitalis: Scooped S-T’s – Hyperkalemia: Wide P & QRS, Peaked T – Hypokalemia: Flat T wave, U wave present – Hypercalcemia: Short Q-T – Hypocalcemia: Long Q-T • Pericarditis: P-R Depression, S-T elevation

•

Clinical Considerations: ECG

Interfering factors:

– Race: ST elevation with T-wave inversion more common in people of African decent.

– Food Intake: High CHO may shift electrolytes and induce ST depression and T-wave inversion.

– Anxiety: May induce ST depression and/ or T-wave inversion.

– Pre-testing activity may alter results.

•

Procedural preparation and aftercare

– Proper lead placement – Instruct patient regarding procedure – Recognize limitations of ECG

Stress EKG

•

Indications

– Definite indications • Atypical symptoms in men or menopausal women • Assess prognosis in patient with known CAD • Assess patient with Exercise-induced dysrhythmia – Possible indications: • Typical or atypical symptoms in menopausal women • Assess response to therapies • Evaluate variant Angina • Serial testing in patient with known CAD

Family Practice Notebook

•

Stress EKG

Contraindications

– Aortic Dissection – Critical Aortic Stenosis – Critical Left Ventricular outflow-tract obstruction – Idiopathic Hypertrophic Subaortic Stenosis (IHSS) – Inability to Exercise to adequate level of exertion – Uninterpretable Electrocardiogram • Left Bundle Branch Block (Adenosine Nuclear needed) • Electronically paced rhythm (Pacemaker) • WPW Syndrome • Abnormal ST segments (>1 mm ST abnormality) – Recent or active cerebral ischemia – Severe uncontrolled Hypertension – Uncompensated Congestive Heart Failure – Unstable Angina – Digoxin Use (Class IIB Recommendation) – Cardiac revascularization within last 5 years

Family Practice Notebook

Ankle Brachial Index

• – – –

Technique

• • • • • • • • Measure highest systolic reading in both arms Record first doppler sound as cuff is deflated Record at the radial pulse Use highest of the two arm pressures Measure systolic readings in both legs Cuff applied to calf Record first doppler sound as cuff is deflated – – Use doppler ultrasound device Record dorsalis pedis pressure Record posterior tibial pressure Use highest ankle pressure (DP or PT) for each leg Calculate ratio of each ankle to brachial pressure Divide each ankle by highest brachial pressure

Family Practice Notebook

Ankle Brachial Index •

Interpretation

– Ankle-Brachial ratio >0.95: Normal – Ankle-Brachial ratio <0.95: Peripheral Vascular Disease – Ankle-Brachial ratio <0.6: Intermittent Claudication – Ankle-Brachial ratio <0.5: Multi-level disease – Ankle-Brachial ratio <0.26: Resting ischemic pain • Ankle-Brachial ratio <0.2: Gangrenous extremity

Family Practice Notebook

Carotid Evaluation / Ultrasound

•

Interpretation of carotid bruit

– Degree of stenosis by atherosclerotic Plaque • Minimum stenosis causing bruit: 50% (<3 mm lumen) • Prolonged, high-pitched bruit: >75% (1.5 mm lumen) – Location • Plaque involves posterior wall of common carotid • Affects bifurcation and flow into internal carotid • Risk of distal thrombus formation in internal carotid – Carotid bruit associated risk of stroke at 1 year • Asymptomatic carotid bruit: 1% risk at 1 year • Transient Ischemic Attack history: 1.7% risk • Other studies question bruit significance

Family Practice Notebook

Carotid Evaluation / Ultrasound •

Evaluation

– Carotid Artery Duplex Ultrasonography • Standard diagnostic tool for carotid stenosis • Less expensive than MRA • Accuracy for diagnosing severe carotid stenosis – Test Sensitivity: 86% – Test Specificity: 87% – Carotid Magnetic Resonance Angiography (MRA) • Better than ultrasound at defining carotid anatomy • Accuracy for diagnosing severe carotid stenosis – Test Sensitivity: 95% – Test Specificity: 90%

Family Practice Notebook

Echocardiogram

•

Indication

– Every patient with Congestive Heart Failure! – Distinguishes • Systolic Dysfunction • Diastolic Dysfunction – Identify underlying valve disease – Identify underlying ischemic heart damage – Quantify Congestive Heart Failure severity

Echocardiogram •

Assessment

– Chamber size (diastolic and end-systolic dimensions) • Left Ventricular Hypertrophy • Left Atrial Enlargement – Ejection Fraction (EF) • Systolic Dysfunction: EF < 45% • Diastolic Dysfunction (isolated): EF > 50% • Echocardiogram accuracy is +/- 5% at best – Heart Valve Function and dysfunction – Wall thickness and wall motion abnormalities

Family Practice Notebook

Thrombolysis

• Needed when the intrinsic clotting mechanisms are activated – Arrhythmias – Fibrillation – Prosthetic valves – Hyper-coaguable (thick) blood • High Fibrinogen • Dehydration • Multiple sites in the clotting cascade can be affected

Anti thrombotics MOA Outpatient

Warfarin [Coumadin]

Vitamin K antagonist (Extrinsic) Factors 2,7,9,10 Uses

Thrombosis, rheumatic heart disease, embolism, ischemic heart disease

Adverse Effects Other

Prolonged bleeding, hemorrhage, diarrhea, fever, rash Monitor pro thrombin time

Antithrombotics Mainly IV / inpatient

Heparin

MOA Uses Adverse Effects Other

Inhibits clotting factors by binding to

antithrombin III (AT3) and ENHANCING the thrombin blockade of AT3.

Prevention of deep vein thrombosis, embolism, DIC Hemorrhage, cutaneous necrosis, chills, pruritus, fever Administer cautiously in men struating women, patients with liver disease or blood disease

CLOTTING PATHWAYS Intrinsic Pathway: Blood trauma (turbulence and viscosity) or collagen and blood contact.

Measured by PT/INR

Drugs: Warfarin, ASA, Vitamin E, EFA’s

Extrinsic Pathway: Damage outside of blood vessels.

Measured by: PTT

Factors 2-7-9-10 Drugs: Heparin

Antithrombin III keeps Thrombin INACTIVE PROTHROMBIN ACTIVATOR

made up of V&X: Started by X alone and V becomes active with + feedback

Antithrombotics

Clopidogrel [Plavix] Aspirin (ASA)

MOA Uses Adverse Effects

Prevent formation of platelet aggregating substance: thromboxane A2 (TxA2) – The pro inflammatory cytokine produced by COX activity along with PG2 in the arachadonate cascade.

Reduce risk of MI, Stroke Salicylism (ASA), GI distress, bleeding, tinnitus, rash, occult blood TTP(Plavix)

ASA for Prevention

• Most patients use 75-162mg / day “low dose ASA” – Average is one 81mg ASA (baby aspirin) •

Am J Cardiol

2008;102:396-400 compared the effects of aspirin 300 mg/day and combined therapy with aspirin 100 mg/day and clopidogrel 75 mg/day on platelet function – Both strategies significantly decreased ADP- and collagen-induced platelet aggregation, the authors report: • 18 of 30 patients treated with aspirin 300 mg/day and • 25 of 30 treated with aspirin 100 mg/day and clopidogrel 75 mg/day had adequate platelet inhibition.

• "Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin," the investigators conclude.

Clopidogrel (Plavix) Rx:

• 75 mg Tablets • Preventive: 75mg qd • Acute (STMI): 300mg loading dose then 75mg qd • Literature lists continuing ASA Rx as well

Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.

N Engl J Med. 2006; 354(16):1706-17 (ISSN: 1533 4406) • CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors.

Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.

Cardiac Function - Basics

Cardiac Function

• Electrical function – Creates the rhythmic pumping of blood via muscular contraction – When irregular creates • Arrhythmias • Extra beats • Hydraulic function – Mass movement of blood through the chambers – Pushed by muscle contraction – Controlled by valves in the system – When irregular creates • Murmurs • Aberrant blood flow

Cardiac Muscle Physiology EPI EPI CA ++ Channels Beta blockers B-1 Adrenergic receptor CA ++ Influx Ca ++ Adenylate cyclase Cross Bridge Formation Cyclase-a ATP cAMP Prot. Kinase Prot.Kinase-a “Phosphorylation”

CA ++ Channel Blockers

Tension Generation

Cardiac AP and Ca++ Channel

Ca++ Channel Open

Carnitine at the Mitochondrial Membrane

Drugs to correct rhythm disturbances:

• These drugs are used to “calm” the electrical impulses in the heart.

• This “calming” creates less aberrant heart beating • These drugs come in four classes – Two classes are also anti-hypertensive drugs – Two classes are specifically rhythm agents

Class I Anti arrhythmics Digoxin Cardiac Glycoside MOA

Inhibits the sodium/potassium pump to increase intracellular calcium.

Calcium drives the cardiac AP plateau.

Uses Adverse Effects Other

CHF, Fatigue paroxysmal atrial tachycardia, atrial flutter, arrhythmias muscular weakness atrial fibrillation, agitation blurred vision anorexia nausea

(also) Lidocaine Quinidine **NOT Quinine!

Decreases automaticity, conduction velocity and prolongs refractory period Has anticholinergic effects Atrial flutter atrial fibrillation premature atrial and ventricular depolarization Arrhythmia, nausea vomiting diarrhea

cinchonism

fever vertigo headache Monitor blood levels.

Toxicity may be life threatening. Yellow halo around vision may develop.

Prolongs QRS and QT intervals on EKG

Cinchonism!

• Quinine AND Quinidine: • Tinnitus / Hearing Loss • Headache / Nausea • Dizziness / Vertigo • Visual changes

Digitalis / Quinidine Rx:

• Digitalis: – (Capsules 0.05, 0.1, 0.2mg::Tabs 0.125, 0.25 mg) – Dose 0.05 to 0.35mg bid – Therapeutic dose levels in 7-21 days – Measure trough level; Effective level 0.8-2 ng/mL • Quinidine: – (Sulfate; 200, 300mg:: Gluconate; 324mg ER) – Dose 300-400mg sulfate q-6hrs – Dose 324 ER q-8-12hrs – Measure trough level 30-35 hours after starting or changing therapy; Effective level 2-6 mcg/mL

Antiarrhythmics MOA Adverse Effects Class II

Beta Blockers

Class III

Amiodarone

•delay in repolarization •prolongation in AP •slowing of electrical conduction •reduction in SA node fct.

•decreased conduction through accessory pathways

Class IV

Calcium Channel Blockers

•About 7 out of every 10 patients will experience some type of reaction, and between 1 in 20 and 1 in 5 will experience side effects that are severe enough to stop the medication. •The most severe side effect related to the lungs. These reactions can be fatal. (One in 10 of those that develop lung toxicity will die.) •rare, fatal liver toxicity has occurred

Other

Diuretics

Na+ HANDLING ALONG THE NEPHRON

•

Numbers = % Na

• •

Arrows = Direction of flow PROXIMAL TUBULE

–

Reabsorbs 67% (2/3) Na & H2O

–

Reabsorbs all Glucose, HCO3, & Amino Acids

–

Reabsorbs Na via Cotransport with Glucose, AA’s, PO4; And via Countertransport in the Na+ / H+ Exchange.

–

Site of Carbonic Anhydrase Inhibitor activity (Blocks HCO3 reabsorption)

•

THICK ASC. LOOP of HENLE

– – –

Reabsorbs 25% of Na Na-K-Cl cotransporter Site of Loop Diuretic action

•

DISTAL TUBULE / COLL . DUCT

–

Reabsorbs 8% Na via. Na-Cl cotransporter

–

Site of thiazide diuretic action

Na+ HANDLING ALONG THE NEPHRON

•

PROXIMAL TUBULE

–

Reabsorbs 67% (2/3) Na & H2O

–

Site of Carbonic Anhydrase Inhibitor activity (Blocks HCO3 reabsorption)

•

THICK ASC. LOOP of HENLE

– –

Reabsorbs 25% of Na Site of Loop Diuretic action

•

DISTAL TUBULE / COLL . DUCT

–

Reabsorbs 8% Na via. Na-Cl cotransporter

–

Site of thiazide diuretic action

Antihypertensive/ Diuretics MOA Uses Chlorothiazide (Hydrochloro thiazide HCTZ) –

Inhibits sodium and chloride re absorption in

distal tubule

resulting in a decrease in the glomerular filtration rate HTN Edema

Adverse Effects Other Hypokalemia,

oliguria, anuria, GI disturbance, hypercalcemia,

hyperglycemia

, hyperuricemia, renal failure C.I. in patients with hypersensitiv -ity to thiazide or

sulfonamide drugs Furosemide [Lasix]

Loop diuretic, inhibits sodium and chloride re absorption in the

Loop of Henle

Edema, HTN

Hypokalemia,

oliguria, anuria, GI disturbance, hypercalcemia,

hyperglycemia

, hyperuricemia, ototoxic, hypovolemia

Antihypertensive/ Diuretics MOA Triamterene

Potassium sparing diuretic acts on

distal tubules Uses

Edema, HTN

Adverse Effects Other **Hyperkalemia,

nausea, vomiting, diarrhea May turn urine blue Folic Acid Base

(Often in combination with HCTZ as “Maxzide” Spironolactone Aldosterone antagonist

Edema HTN Some endocrine uses (PCOS…)

Same,

plus breast deformity and tenderness Multiple toxicities

ALDOSTERONE Spironolactone BLOCKS!

Leads to Na EXCRETION (in urine) and K retention (in blood)

Diuretics

• HCTZ – 12.5mg capsules; 25, 50, and 100mg tablets • Edema: 50-100mg qd until edema resolved – Short term only – Max Dose 200 mg acutely • HTN: – 12.5 – 50mg qd • HCTZ / Triamterene – 25mg / 37.5mg - Maxzide; 50mg / 75mg – Maxzide-25 • Furosemide – 20, 40, and 80mg Tablets • Edema: 80 mg qd (may increase as required up to 600mg total daily) • HTN: 40mg bid

Antihypertensive Drugs:

• Beta Blockers

–

END IN “-OLOL”

• ACE Inhibitors

–

END IN “-PRIL”

• ARB’s (Angiotensin Receptor Blockers)

–

END IN -SARTAN

• Catecholamine Agent – ONLY ONE:

Reserpine

• Calcium Channel Blockers – All the rest!

Beta-Blockers

Cardiac Muscle Physiology EPI EPI CA ++ Channels Beta blockers B-1 Adrenergic receptor CA ++ Influx Ca ++ Adenylate cyclase Cross Bridge Formation Cyclase-a ATP cAMP Prot. Kinase Prot.Kinase-a “Phosphorylation”

CA ++ Channel Blockers

Tension Generation

Antihypertensives Beta Blockers Atenolol Acebutolol Betaxolol Bisoprolol Esmolol Metoprolol MOA



1 adrenergic receptor

blocker, decreases cardiac output and renin release

Uses

Hypertension, angina

Adverse Effects Other

Fatigue, drowsiness, vertigo, dizziness, bradycardia, hypotension, bronchospasm, CHF

Enhance effects of digitalis Propranolol Carteolol Nadolol Pindolol Sotalol Timolol

Blocks

both



1 and



2

adrenergic receptors Hypertension, angina, arrhythmias, migraines, essential tremors Fatigue, bradycardia, hypotension, lethargy, nausea, vomiting, diarrhea, CHF Abrupt discontinuati on may cause tachycardia and rebound hypertension

Beta Blockers

• Atenolol (Tenormin) – 25, 50 or 100mg tablets – HTN: • 50 mg qd • Increases to 100 mg qd maximun – Migraine Prophylaxis • 100mg qd

Calcium Channel Blockers

Cardiac Muscle Physiology EPI EPI CA ++ Channels Beta blockers B-1 Adrenergic receptor CA ++ Influx Ca ++ Adenylate cyclase Cross Bridge Formation Cyclase-a ATP cAMP Prot. Kinase Prot.Kinase-a “Phosphorylation”

CA ++ Channel Blockers

Tension Generation

Cardiac AP and Ca++ Channel

Ca++ Channel Open

Antihyper tensives Ca++ Channel Blockers

Bepridil Mibefradil Verapamil [Isopten] Diltiazem [Cardizem] Amlodipine Felodipine Nicardepine Nefidipine Nifedipine [Procardia]

MOA

Calcium channel blocker Calcium channel blocker Calcium channel blocker

Uses Adverse Effects Other

Angina, hypertension Angina, hypertension, atrial fibrillation or flutter Angina, hypertension Constipation, hypotension, dizziness, edema, nausea, CHF Headache, edema, dizziness, arrhythmias, CHF, nausea, constipation, rash Dizziness, CHF, MI edema, headache, weakness, nausea, Increased levels with cimetidine Increased levels with cimetidine Capsule passed in stool, medicine released in gut

Calcium Channel Blockers

• Amlodipine (Norvasc) – 2.5, 5 and 10mg tablets – Angina • 5 to 10 mg qd – HTN • 2.5 to 5 mg qd • Maximum dose is 10 mg qd

Angiotensin Agents

ALDOSTERONE – RENIN – ANGIOTENSIN SYSTEM ACE-I - BLOCK ARB BLOCK

Antihypertensives MOA ACE Inhibitors

Captopril Benazepril Enalapril Lisinopril Fosinapril

Uses

Inhibits ACE [angio tensin converting enzyme] in the lungs.

Hyper tension, heart failure

Adverse Effects Other Dry persistent cough

Tachycardia, hypotension, urticaria, rash, Renal dysfunction headache

Hyperkalem ia

Contra indicated in preg nancy

Antihypertensives MOA ARB’s

Candi-/ Irbe Epro- / Lo Telme- / Val (sartan) Blockade of ANG-2 Receptors

Uses Adverse Effects

Hyper tension in those with ACE intolerance due to Cough Hypotension Renal Dysfunction

Hyperkalemia

Angiotensin Agents

• ACE Inhibitors – Quinapril (Accupril) • 5, 10, 20 and 40mg tablets • Dose for HTN 10-20 mg to start • Maximum dose 80 mg qd • ARB’s – Candesartan (Atacand) • 4, 8, 16 and 32 mg tablets • 16 mg qd starting dose • Often used 8 – 16 mg bid

No "clinically meaningful difference" in hypertension

• "With the exception of rates of cough, the available evidence does not strongly support the hypothesis that ACE inhibitors and ARBs have clinically meaningful differences in benefits or harms for individuals with essential hypertension," according to the report's authors, led by Durham, NC).

and adverse events.

Dr David B Matchar

(Duke Center for Clinical Health Policy Research, • He and his colleagues analyzed 69 reports based on 61 randomized and observational studies that lasted at least three months and directly compared an ACE inhibitor and an ARB in adults with essential hypertension and evaluated meaningful end points like blood pressure control, treatment compliance,

Peripheral Anti-Adrenergic

Peripheral anti adrenergic

Reserpine

MOA Uses Adverse Effects Other

Depletes catecholamine stores in PNS [and maybe CNS] Essential hypertension Drowsiness, sedation, nervousness, depression, Decr. HR, nasal congestion, nausea / diarrhea Parasympathetic Predominance Do NOT administer

MAO inhibitors and Reserpine

within two weeks of each other

Rx of Reserpine:

Available in 0.1 and 0.25mg tablets Common Rx’s: - 0.1 qd to bid - 0.25 qd to bid Do not use in catecholamine responsive depressives.

Overdose symptoms include hyper-parasympathetic activity.

But doesn’t Rauwolfia and Reserpine use make people kill themselves?

Lets go through this now:

Peripheral anti adrenergic MOA Uses Adverse Effects Other

Reserpine Depletes catecholamine stores in PNS [and maybe CNS] Essential hypertension

These are RARE in hyper catecholamine patients.

Drowsiness, sedation, nervousness, depression, Decr. HR, nasal congestion, nausea / diarrhea Parasympathetic Predominance Do NOT administer

MAO inhibitors and Reserpine

within two weeks of each other

Rauwolfia and Reserpine

• Reserpine Tablets: – 0.1 and 0.25mg available – Dose is 0.1 – 0.25 qd – bid • Rauwolfia: – Watch tincture concentration – Average dose 1-3 mL qd - bid

Anti-Anginal Drugs

Anti-anginal drugs MOA Uses Nitroglycerin

Increases blood supply to heart; decreases preload and afterload Angina

Amyl Nitrate

Unknown, thought to be dilation of arterial and venous system Angina

Papaverine HCl

“Cardiac vessel dilation”

Calcium Channel Blockers

See above

Angina Angina

Adverse Effects Other Headache,

dizziness, hypotension, tachycardia, bradycardia, rash Throbbing headache, dizziness, hypotension, tachycardia, bradycardia, Similar to Nitro.

Antidote for cyanide poisoning No longer used

Nitrate Rx:

• NTG – SL-Tablets 0.3, 0.4 or 0.6mg

– Acute angina: • Dose 1 SL tablet up to 1 tablet every 5 minutes for 3 doses • Other dose forms available: – Spray, Cream, Long Acting Capsules

Angina Rx:

• L-Arginine PO dose – 1000 – 2000mg bid • Magnesium Glycinate PO dose – 100-300mg bid • Zinc PO dose – 20-50mg bid (taken in the middle of a meal to decrease nausea!)

Lipid Management

Basics:

• HDL: – “Good” although there are better and worse forms.

• Acts more like a hormone than a lipid molecule • LDL: – “Bad” although there are better (larger) and worse (smaller) forms.

– Carry OXIDANTS!

– Generally LOWERING these makes one less inflammatory • Triglycerides: – Stimulated in production by CHO intake – Elevations often indicate Pro-Inflammatory status and disorders of Insulin – Sugar biochemistry

LDL Oxidation: The LDL has the potential to carry an incredible load of free radical.

Anti-Oxidant effects of Vitamins E, C, GSH and the RBC - Lipid – Plasma Interaction

RBC Reduced Glutathione Plasma ASC LDL Toco

R

Toco Oxidized Glutathione ASC

R

DHA LDL + R = “oxidized LDL”

Cholesterol Transport

Cellular Cholesterol Balance

High Cholesterol Types

• Lipoprotein Electrophoresis – 5 Sub categories of hyperlipidemia • Fredrickson’s Genotypes – Types 2 & 4 are most common • Type 4 is 1-2 X more common than Type 2 – Generally High TC,

TG’s

(higher than TC), and LDL – Responds to carbohydrate restriction – Poor response to low fat diets • Type 2 – generally High TC, LDL, and

NORMAL TG’s

– Responds better to reduced fat diets

Sugar / Insulin and TG Synthesis

BLOOD

TG’s to Blood

CYTOSOL CHO

 AcetylCoA [AcetylCoA Carboxylase]

Insulin(+)

Malonyl CoA

Palmitate (-)

CPT-1

MITOCHONDRIA Acyl Units Beta Oxidation Energy Acyl Units

Esterify to TG’s

Lipid Lowering Agents Lovastatin [Mevacor] Simvastatin [Zocor] Atorvastatin [Lipitor] Fulvistatin [Lescol] Pravistatin [Pravacol] MOA HMG CoA reductase inhibitor Uses

Hyperlipidemia

Adverse Effects

Check AST and ALT prior to Rx, and at 6 weeks post-Rx.

Other

GI distress, headache, dizziness, abdominal cramps, rash, liver toxic, rhabdo myaloysis Monitor liver function Rx along with 75-100 mg Co-Q10 minimum.

Discontinue if patient has muscle pain concomitant to Rx – EVEN if LFT’s are normal.

Statin Rx:

• Atorvastatin (Lipitor) – 10, 20, 40 and 80mg tablets • Dose 10 to 20mg qd • Start at 40mg qd if LDL reduction need is greater than 45% • Maximum dose 80mg qd • Draw Lipids and LFT’s 4 weeks after therapy initiation or does adjustment

A Multicenter Placebo Controlled Dose Ranging Study of Atorvastatin

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 2, 119-123 (1998) • Patients received placebo or atorvastatin 10, 20, 40, 60, or 80 mg once daily. • Adjusted mean decreases in LDL cholesterol for patients receiving atorvastatin 10, 20, 40, 60, and 80 mg were 37%, 42%, 50%, 52%, and 59%, respectively, compared with a mean increase of 0.3% for patients receiving placebo

Lipid Lowering Agents Cholestyramine [Questran] MOA Uses

Combines with bile acid to form an insoluble compound that is excreted Hyper lipidemia

Adverse Effects

Constipation, fecal impaction, abdominal pain, nausea

Other

Reduces absorp tion of fat soluble vitamins

Lipid Lowering Agents Niacin MOA

Stimulates hepatic lipid metabolism

Uses

Hyper lipid emia

Adverse Effects

Niacin flush, rash, GI distress

Other

Give with B-Complex and Vitamin C to avoid Hepatic Effect.

May be Rx’d alone or in a combination of Niacin and a low dose statin.

Rx a high potency B-Complex AND Vitamin C (gram per gram of Niacin).

Rx takes at least 1500 – 2000 mg daily to have any significant effect on lipids.

SLOW release is generally better tolerated.

Slow release is NOT more dangerous than immediate release if Rx’d properly.

LOWERS: TC, LDL AND TG RAISES: HDL

Niacin Rx:

• Niacin Extended Release (Niaspan) – 250, 500, 750 or 1000mg tablets • Start with 1000 mg hs, work up to 1500 – 2000mg hs – Avoid spices, tannins etc with medication – 81mg ASA taken with the Niacin reduces flushing

Advicor Rx:

• Lovastatin / Niacin combination: – 20/500, 20/750, 20/1000 or 40/1000mg – Dose is 1 po qhs

Fibrates

• Fenofibrate (TriCor…) – Multiple dose formats • To lower Triglycerides – 48 – 145 mg qd – Maximum dose 145mg

Lovaza

• Omega-3-acid ethyl esters (1 gram capsules) – Normal Sig is 2 capsules bid • Indicated alone or with Statins in patients with high (200-499) or very high (>500) triglycerides.

– Alone in very high TG – With 40 mg Statin in high TG

Cardiovascular (CV) causes of chest pain

• Angina:

Covered later

PERICARDITIS

• Usually more localized, sternal or over cardiac apex • sharp, stabbing, knife-like pain • lasts hours to days • aggravated by deep breathing or lying supine and relieved by sitting up and leaning forward • may auscultate friction rub

DISSECTING AORTIC ANEURYSM

• anterior chest pain, may radiate to back • excruciating, tearing pain; sudden onset, lasts hours to days • pain unrelated to anything • BP lower in left arm

Noncardiac causes of chest pain

• • •

GI disorders

: peptic ulcer, esophageal reflux, hiatal hernia, cholecystitis; pain usu burning, cramping, aching; worse supine; may be meal related

Musculoskeletal disorders

: variable location; aching pain, made worse with movement or palpation; touching surface of chest aggravates the pain.

Spontaneous Pneumothorax

: unilateral location; sharp, localized; sudden onset lasting many hrs; dyspnea, SOB, painful breathing

Noncardiac causes of chest pain

• • •

Pulmonary Embolism

: pleurisy type pain, dyspnea, pleural rub, pain over area of infarction; hemoptysis with lg infarction

Pulmonary Hypertension

: substernal pain, pressure, dyspnea, accentuated pulmonary second heart sound

Anxiety States

: localized pain, sharp, burning; moves from place to place, brief duration,  with emotional situations; frequent sighing

EKG

Wave Propagation

P-wave means Atria!

No p-wave! Ventricles!

Axis!

EXTREME RAD

Deviation!

LAD HAPPY!!

RAD

Infarction causes deflection of the Axis! (RAD)

Hypertrophy Accentuates the Axis (LAD)

Angina Pectoris

Clinical syndrome caused by Myocardial ischemia (usually from CAD)

Angina Pectoris

• Transient precordial pain, brought on by exertion and relieved by rest • Pain may be vague or crushing; may radiate to left shoulder, jaw, throat, teeth, arms • Pain may be worse after meal or in cold weather; may change as collateral circulation builds up • Usually relieved with sublingual nitroglycerin (NTG) within 2-3 min.

• EKG often normal with attacks – exercise test may show ST abnormalities that help with diagnosis (ST depression = ischemia)

Unstable Angina

• More severe form of angina • Same etiology as exertional angina • Variant angina (Prinzmetal’s angina) = angina at rest with ST segment elevation during attack • May occur at same time of day • Felt to be from coronary artery spasm

Acute Myocardial Infarction

• When insufficient coronary blood supply persists after myocardial energy reserves have been depleted, the myocardial cells become irreversibly ischemic and the process of necrosis termed “myocardial infarction” • Pain not relieved with NTG • Apprehension and sense of “doom” • Most MI’s occur at 9 a.m. on Mondays

Five major signs and symptoms of MI

• pain or discomfort in the jaw, neck, or back • feeling weak, lightheaded, or faint • chest pain or discomfort • pain or discomfort in the arms or shoulder • and shortness of breath

MI

• All symptoms typically come and go on a 3-5 minute cycle.

• In women the signs may be: – More significant nausea – Back pain (above the kidney area) – No neck or arm pain, often little chest pain – These signs and symptoms cycle on a 3-5 minute rate as well

Acute Myocardial Infarction

• Abnormal EKG with Q waves • CPK MB fraction elevated • ECHO shows abnormal left ventricular wall motion

Heart Failure

Congestive Heart Failure

• Clinical syndrome in which the heart fails to pump enough blood to meet the body’s need • Leads to – Dyspnea On Exertion – Paroxysmal Nocturnal Dyspnea – Orthopnea

Diastolic Heart Failure

• Classically, heart failure has been almost synonymous with left ventricular systolic failure (pump failure) • Diastolic dysfunction of the left ventricle occurs when there is impairment of relaxation of the ventricle resulting in delayed filling and increased pulmonary venous pressure • This combined with secondary compensatory tachycardia results in  left ventricular volume

Adaptive Mechanisms in CHF

• • • •

Ventricular dilation

—will eventually lead to  diastolic pressure and pul edema (left failure) and/or systemic edema (right failure)

Reduced blood flow to the kidneys

 and water retention and  salt blood volume with 2 º HBP (  afterload)

Sympathetic stimulation

increases venous tone, thus shunting blood from the peripheral tissues to the heart causing  BP

Tachycardia

and increased contractility may precipitate ischemia in pts with CAD

Left CHF

• Cardinal clinical symptoms are DOE, chronic dry cough and fatigue • Tachycardia, cardiac asthma, productive rust colored sputum, rales, displaced apical impulse, S-3, S-4 gallop rhythms, right sided pleural effusions, reduced carotid pulse • Nocturia due to  renal perfusion lying down and exercise intolerance due to  blood flow to muscles.

• Pallor, tachypnea, restlessness, low BP

Right CHF

• Fatigue, distended neck veins, pedal edema, ascites, pitting edema, large liver, tricuspid regurgitation murmur and cyanosis; orthopnea and PND.

• Diseases that produce these sx include lung disease, pul embolus, volume overload, mitral stenosis.

Pulmonary Heart Disease (Cor Pulmonale)

• Right ventricular hypertrophy and eventual failure from pulmonary diseases • Causes include: – COPD – Pulmonary fibrosis or emboli – Scleroderma – Primary pulmonary hypertension – Alveolar hypoxia from any cause

Cor Pulmonale

• Chronic cough, exertional dyspnea, wheezing, fatigue, weakness, cyanosis, clubbing epigastric pulsations, distended neck veins, hepatomegaly, polycythemia • CXR shows RVH • PFTs show underlying lung disease • ECHO shows right ventricular disease

Disturbances of Rate and Rhythm

Normal Sinus Rhythm

• Impulses originate in SA node • Regular rate of 60-100/min in adults • Each P followed by QRS

Normal Sinus Rhythm

Sinus Arrhythmia

• Similar to normal sinus rhythm • Effect of respiration changes the frequency the SA node discharges.

Sinus Bradycardia

• Similar to NSR except the rate is < 60/min in adults • Physiological bradycardia occurs in healthy individuals (usually athletes) with  vagal tone

Sinus Bradycardia

Sinus Tachycardia

• Impulses originate in SA node at rate of 100-160/min in adults • QRS follows each P wave

Atrial Premature Beat (APB)

• Impulse is discharged prematurely by an irritable focus in the atria • The further from the SA node the ectopic focus is, the more abnormal will be the P configuration • PR is variable, but QRS is normal

Atrial Premature Beat (APB)

Atrial Tachycardia aka Supraventricular Tachycardia SVT • Impulses originate in an atrial pacemaker at rate of 140-250/min • QRS is usually narrow • At very rapid rates, only every 2 nd followed by QRS (2:1 block) P may be • Vagal stimulation can terminate the AT • Common, occurs in young people with no known heart disease

Atrial Tachycardia

Atrial Flutter

• Impulses originate in an atrial pacemaker at rate of 240-340/min, but some are blocked at the AV node • Atrial activity is represented by saw tooth-like deflections (Flutter waves) • Symptoms of palpitations, sweating weakness, dizziness, syncope • Vagal stimulation has no effect

Atrial Fibrillation

• Impulses originate in multifocal atrial pacemaker at rate of 300-600/min, but only some are conducted to the ventricles • Many patients are asymptomatic • Since there is a deficit in radial and precordial pulse, apical pulse should be taken in patients • Pulse is irregular, irregular • Vagal stimulation has no effect on ventricular rate

Atrial Fibrillation

Premature Ventricular Contractions (PVC)

• QRS is wide (> 0.12 sec), not preceded by P wave • Etiology is an irritable focus in the left or right ventricle that fires prematurely and the impulse is spread to the opposite ventricle with delay producing a bizarre QRS complex • PVCs are forerunners of ventricular tachycardia if they are frequent (> 5/min) • May feel palpitations or be asymptomatic

Premature Ventricular Contractions

Ventricular Tachycardia

• By definition, VT consists of at least three consecutive QRS complexes originating from the ventricles and recurring at a rapid rate (over 120 beats/min).

Ventricular Tachycardia

• Ventricular tachycardia (VT) is a tachydysrhythmia originating from a ventricular ectopic focus, characterized by a rate typically greater than 120 beats per minute and wide QRS complexes • P waves are frequently hidden or may appear as notches at various points on the QRS-T complexes, but at a slower rate • Vagal stimulation has no effect

Ventricular Tachycardia

Ventricular Fibrillation

• Multiple sites in the ventricle fire impulses in an uncoordinated fashion • Ventricular fibrillation is a terminal arrhythmia, uniformly requiring rapid initiation of emergency measures

Sick Sinus Syndrome

•

Sick-sinus syndrome

is a general term used to indicate abnormalities of cardiac impulse formation and intraatrial and AV conduction that may be manifested by various combinations of brady- and tachyarrhythmias • CAD is the most common cause • Symptoms include none, light headedness, fatigue, syncope, confusion, CHF or angina

Heart Block

• Often the presenting sign of heart block is SYNCOPE.

First Degree AV Block

• Impulses originate in SA node • First-degree AV block is defined as a PR interval in excess of 0.2 s at normal heart rates • QRS follows each P wave

Second Degree AV Block

• Second-degree AV block is characterized by intermittent failure of conduction from atria to ventricles and is further subdivided into type I (Wenckebach phenomenon) and Möbitz type II second-degree block

Second Degree AV Block Type I (Wenckebach)

• Impulses originating in SA node are conducted through AV node at progressively slower speed.

• A blocked P wave occurs after 2-5 conducted P waves and then repeats itself (PR interval becomes progressively longer until the QRS is dropped)

Second Degree AV Block Type II (Mobitz)

• In type II second-degree AV block, appropriately timed P waves fail to conduct, but there is not a pattern of progressive PR lengthening.

• Prognosis is not good

Third Degree (Complete) AV Block

• Impulses originate in SA node, but none are conducted through the AV jct.

• In third-degree (complete) AV block, the atrial and ventricular rates are regular but dissociated • Maneuvers by the patient, such as arm movement, standing up, or marching in place, may increase the sinus rate (P waves) without corresponding changes in the ventricular escape rate, confirming loss of AV conduction.

Bundle Branch Block (BBB)

• Impulses originate in SA node, spread through atria, but are blocked through the right or left branches of the bundle of His • Wide QRS • LBBB is more ominous than RBBB

Wolff-Parkinson-White Syndrome (WPW)

• Impulses originate in SA node, spread over atria, but bypass the AV jct. through an accessory bundle with premature activation of the ventricles

Vasculitis

• Large-Vessel Vasculitis – Giant Cell Arteritis – Takayasu's Disease • Medium-Vessel Vasculitis – Polyarteritis Nodosa – Kawasaki's Disease • Small-Vessel Vasculitis – ANCA Associated Small Vessel Vasculitis – Non-ANCA Small Vessel Vasculitis

• •

Small Vessel Vasculitis

Symptoms – Fever – – – – – – – – Weight loss Malaise Myalgias and arthralgias Dyspnea Cough (Hemoptysis may be present) Diarrhea Nausea or Vomiting Abdominal Pain Signs – Dermatologic findings • Palpable Purpura (duration longer than 24 hours) • Urticaria – Pulmonary findings • Interstitial Lung Disease • Pulmonary hemorrhage • – – – Neurologic findings • Peripheral Neuropathy Gastrointestinal findings • Fecal blood positive Differential Diagnosis • Embolic disease • Sepsis • Lymphoma • • Leukemia Myelodysplastic condition – – – – – – Labs – Antineutrophil Cytoplasmic Antibodies (ANCA) – – – – – Complete Blood Count (CBC) Normocytic Anemia Thrombocytosis Chemistry profile (e.g. Chem8) Renal Function tests may show renal insufficiency Liver Function Tests Increased liver enzymes Fecal Occult Blood Urinalysis (Glomerulonephritis) Hematuria Proteinuria

Murmurs:

• S-1 (T/M) ---Systole--- S-2 (A/P)---Diastole---S-1 • Systolic Murmurs: “Big Deal” – May be normal variants – May indicate pathology • (Midsystolic) Aortic / Pulmonic Stenosis • (Pansystolic - Holosystolic) Mitral/Tricuspid Regurgitation, Ventricular Septal Defect • Diastolic Murmurs: BIG DEAL – (Almost) Always indicate heart disease!

• (Diastolic Rumble)Mitral Stenosis • (Decrescendo – Immediate Diastolic Murmur)Aortic Regurgitation

Cardiac Murmurs

• The types of valvular heart disease can be distinguished by the type of murmur heard on auscultation • Stenotic lesions of the aortic and pulmonary valve have an ejection murmur; they are systolic in timing, have a crescendo component and do not completely fill systole until late ( 1  2 1  2 )

Aortic Stenosis (AS)

• Most frequent etiology for AS is senile calcific stenosis; second is calcification of a congenital (bicuspid) valve; third is rheumatic heart dis.

• Sx include syncope, angina, SOB, CHF • Signs include ejection murmur at right 2 nd ICS, weak and delayed peripheral pulses • Diagnosis is by ECHO

Aortic Insufficiency

• SOB, palpitations, angina • Signs include a diastolic murmur that is “blowing” and soft, elevated systolic BP and low diastolic BP • CXR shows signs of CHF and/or cardiomegaly

Mitral Stenosis (MS)

• Usual etiology for pathology is post rheumatic heart disease • SOB, DOE, PND, which are all part of CHF • Murmur is diastolic with an opening snap (due to stiff, thickened valves) followed by a low pitched rumbling sound best heard at the apex or left sternal border. (  2-3 )

Mitral Stenosis (MS)

• EKG may show notched P waves indicating left atrial enlargement • Diagnosis is by ECHO and cardiac cath • Indications for surgery include sx, presence of transvalvular gradient, measured by catheter, of > 4 mm Hg.

Mitral Regurgitation

• Symptoms of dyspnea, fatigue, left ventricular failure • Left ventricle eventually becomes compromised leading to cardiac dilatation • Murmur is pansystoloic, max at apex and radiating to axilla, blowing in quality with prominent 3 rd heart sound • Echo

Tricuspid Stenosis (TS)

• Most frequent etiology is congenital, RHD, neoplasms • Right atrium is  , atrial fib is frequent • EKG shows atrial fib and right atrial  • Dx can be made by Echo

Tricuspid Regurgitation (TR)

• Most frequent etiology for TR is physiologic, as a reflection from left sided heart disease; endocarditis, especially in drug addicts (60% are due to Staph aureus) • Murmur low pitched, blowing, pansystolic, worse with inspiration and heard along left sternal border

Endocarditis

• Infective endocarditis is a microbial infection of the endocardium, usually a subacute bacterial endocarditis (SBE) • Most pts have underlying organic heart dis (abnormal valves, septal defects);High incidence seen in IV drug users • Nonspecific symptoms of cough, dyspnea, arthralgia, diarrhea, pallor, splenomegaly, abd./flank pain from emboli • Petechiae on palate or conjunctiva or in nail beds, splinter hemorrhages • 90% have heart murmurs and a changing murmur with leukocytosis is common

Endocarditis

• Blood cultures are the definitive diagnostic procedure; may be falsely negative in 5% • Echo confirms the vegetations

Myocarditis: Inflammation of the myocardium • Etiology usually caused by infection (viral, most common); toxins, drugs, radiation, immunologic reactions. Often follows a URI • Typically present with heart failure following a febrile illness or with heart failure alone • Symptoms: – fatigue, dyspnea, palpitation, precordial pain through the first few weeks of the infection

Hypertension

Essential Hypertension

• No known cause • There is a natural progression of the disease suggesting early  in blood volume and cardiac output might cause  resistance • This could be mediated by enhanced sympathetic activity or by  circulating levels of angiotensin II

Secondary Hypertension

• Renal artery stenosis • Chronic renal disease • Primary hyper-aldosteronism • Hyper or hypo thyroidism • Pheochromocytoma • Pre-eclampsia • Aortic coarctation • BCP use

Disease of the Aorta

Aneurysms

• Local dilation of the aorta resulting from weakness of the wall with distention • Most common etiology is atheroma; more recently evidence of Chlamydia pneumoniae has been found • 90% of aortic aneurysms are abdominal • Best noninvasive method is ultrasound (98% accurate on determining size)

Rupture rate of aneurysm at 5 yrs

Size of aneurysm % rupture rate 7 cm or greater 6-7 cm 5-6 cm (less than 5 cm) 75% 35% 25% (insufficient data)

Signs and Symptoms of AAA

• Aneurysms < 5 cm are usu asymptomatic • Pain in abdomen or low back • Pulsatile mass (many thin patients will have a pulsatile mass that is normal) • Tenderness over the pulsatile mass • Bruit over the mass (also can be heard in normals)

Aortic Dissection

• Occurs in ascending aorta; caused by a break in the intima allowing blood to flow in a plane between the media and adventitia • Pain is severe, chest or neck; may radiate to back and later to abdomen • Peripheral pulses and BP may be unequal • Syncope, hemiplegia or paralysis of the lower extremities may occur • CT and transesophageal echocardiography

Inflammatory Pericarditis

• Most cases are idiopathic or have a viral etiology • Patients typically complain of sharp central chest pain that worsens with recumbency and is relieved by leaning forward • Pain may be pleuritic in nature and may radiate to the trapezius muscle • Patients may reveal the pathognomonic finding for pericarditis: the

pericardial friction rub

• ECHO is a more accurate test

Cardiac Tamponade

• Results from accumulation of fluid in the pericardial sac; the heart has an inability to contract due to space restriction • Chest pain, dyspnea, cough, tachycardia, tachypnea, pulsus paradoxus (fall in BP > 10 mmHg with inspiration), edema and ascites may be seen