Clinical Pathologic ConferenceClinical Pathologic ConferenceDivision of CardiologyDivision of Cardiology

Andrew BolinAndrew BolinMay 11May 11thth, 2007, 2007

The CaseThe Case Chief Complaint: Irregular Heart Beat, Dyspnea Chief Complaint: Irregular Heart Beat, Dyspnea

and Fatigue.and Fatigue. HPI: A 74 year old white female with a history HPI: A 74 year old white female with a history

of paroxysmal atrial fibrillation for 7 years is of paroxysmal atrial fibrillation for 7 years is referred to the cardiology clinic.referred to the cardiology clinic.

The patient had intermittent paroxysms of The patient had intermittent paroxysms of atrial fibrillation while taking flecainide for 5 atrial fibrillation while taking flecainide for 5 years. In the month prior to referral, she was years. In the month prior to referral, she was hospitalized twice for rapid atrial fibrillation. hospitalized twice for rapid atrial fibrillation.

The CaseThe Case Before the first hospitalization, the patient Before the first hospitalization, the patient

reported symptoms of: paroxysmal nocturnal reported symptoms of: paroxysmal nocturnal dyspnea, orthopnea and dyspnea on exertion.dyspnea, orthopnea and dyspnea on exertion.

During the first hospitalization, flecainide was During the first hospitalization, flecainide was discontinued and warfarin and metoprolol were discontinued and warfarin and metoprolol were started. She ruled out for an acute myocardial started. She ruled out for an acute myocardial infarction and a dipyridamole thallium study infarction and a dipyridamole thallium study did not demonstrate ischemia. An echo-did not demonstrate ischemia. An echo-cardiogram revealed normal left ventricular cardiogram revealed normal left ventricular function and a mildly enlarged left atrium.function and a mildly enlarged left atrium.

The CaseThe Case Two weeks prior to her second hospitalization, Two weeks prior to her second hospitalization,

the patient experienced the sudden onset of: the patient experienced the sudden onset of: fatigue, decreased endurance, irregular heart fatigue, decreased endurance, irregular heart beat, constant chest pressure and profound beat, constant chest pressure and profound dyspnea on exertion.dyspnea on exertion.

Prior to this illness, the patient could ambulate for Prior to this illness, the patient could ambulate for thirty minutes without fatigue or dyspnea. On the thirty minutes without fatigue or dyspnea. On the day of consultation she experienced dyspnea on day of consultation she experienced dyspnea on walking 20 yards.walking 20 yards.

Review of Symptoms: Positive for: 10 pound Review of Symptoms: Positive for: 10 pound weight gain, diffuse chronic myalgias, and anxietyweight gain, diffuse chronic myalgias, and anxiety

Past Medical HistoryPast Medical History Hypertension for 11 yearsHypertension for 11 years Breast Cancer: underwent left Breast Cancer: underwent left

mastectomy and chemotherapy 14 years mastectomy and chemotherapy 14 years before. No radiation therapy.before. No radiation therapy.

Recurrent Urinary Tract InfectionsRecurrent Urinary Tract Infections

Social History Family HistorySocial History Family History

Married to retired Married to retired Methodist ministerMethodist minister

Two adult childrenTwo adult children No alcohol, tobacco No alcohol, tobacco

or illicit drugsor illicit drugs No unusual No unusual

exposuresexposures

Mother died of Mother died of congestive heart congestive heart failure at age 79failure at age 79

Sister breast cancerSister breast cancer Sister “bone cancer”Sister “bone cancer”

MedicationsMedications Metoprolol 25 mg BIDMetoprolol 25 mg BID CoumadinCoumadin Hydrochlorothiazide Hydrochlorothiazide

25 mg Daily25 mg Daily Celexa 10 mg Daily Celexa 10 mg Daily Aspirin 81 mg DailyAspirin 81 mg Daily Bactrim DS three Bactrim DS three

days per weekdays per week

Allergies: Allergies: MacrodantinMacrodantin

Physical ExamPhysical Exam Blood Pressure 148/78 (in both arms) Blood Pressure 148/78 (in both arms)

Pulse 90 Respirations 18Pulse 90 Respirations 18 Neck: normal jugular venous pressure, Neck: normal jugular venous pressure,

symmetric brisk carotid upstrokes symmetric brisk carotid upstrokes without bruits, no lymphadenopathywithout bruits, no lymphadenopathy

Lungs: clear to auscultation, dullness to Lungs: clear to auscultation, dullness to percussion in right base percussion in right base

Physical ExamPhysical Exam Cardiac: normal point of maximal impulse, Cardiac: normal point of maximal impulse,

normal S1, physiologically split S2, no normal S1, physiologically split S2, no murmurs, rubs or gallops, strong and murmurs, rubs or gallops, strong and symmetric peripheral pulsessymmetric peripheral pulses

Benign Abdominal ExamBenign Abdominal Exam Extremities: no clubbing, cyanosis or edemaExtremities: no clubbing, cyanosis or edema Musculoskeletal: tenderness to palpation in Musculoskeletal: tenderness to palpation in

trapezius and shoulder girdle bilaterallytrapezius and shoulder girdle bilaterally

StudiesStudies Electrocardiogram: atrial fibrillation, Electrocardiogram: atrial fibrillation,

incomplete right bundle branch block incomplete right bundle branch block and nonspecific ST-T abnormalitiesand nonspecific ST-T abnormalities

Chest X-ray: possible right pleural Chest X-ray: possible right pleural effusioneffusion

Transesophageal Echocardiogram: Transesophageal Echocardiogram: unusual thickening of left atrial walls, unusual thickening of left atrial walls, small pericardial effusionsmall pericardial effusion

StudiesStudies Chest CT: pericardial effusion and Chest CT: pericardial effusion and

bilateral pleural effusions, biapical bilateral pleural effusions, biapical pleuroparenchymal scarringpleuroparenchymal scarring

Cardiac MRI: atrium unremarkableCardiac MRI: atrium unremarkable Labs: CBC, E-group, BUN, Creatinine, Labs: CBC, E-group, BUN, Creatinine,

TSH, Troponin and CK were all within TSH, Troponin and CK were all within normal limits.normal limits.

Right ThoracentesisRight Thoracentesis Consistent with Transudative EffusionConsistent with Transudative Effusion WBC 485, Lymphocytes 89%WBC 485, Lymphocytes 89% Flow Cytometry: Consistent with a Flow Cytometry: Consistent with a

Reactive Effusion.Reactive Effusion. Cytology: No Malignant CellsCytology: No Malignant Cells

Case SummaryCase Summary Elderly White Female with A-fibElderly White Female with A-fib Progressive Symptoms of CHF Over Weeks Without Progressive Symptoms of CHF Over Weeks Without

Echocardiographic Evidence of LV DysfunctionEchocardiographic Evidence of LV Dysfunction Transudative Lymphocytic Bilateral Pleural Transudative Lymphocytic Bilateral Pleural

Effusions Effusions Biapical Pleuroparenchymal ScarringBiapical Pleuroparenchymal Scarring Pericardial Effusion Without Evidence of Pericardial Effusion Without Evidence of

TamponadeTamponade Incomplete Right Bundle Branch BlockIncomplete Right Bundle Branch Block Abnormal Left Atrial WallsAbnormal Left Atrial Walls

Case SummaryCase Summary The Patient Has a Pathologic Process The Patient Has a Pathologic Process

Involving the Pericardium and Involving the Pericardium and Myocardium that is Not Related to Myocardium that is Not Related to Valvular or Ischemic Disease. Valvular or Ischemic Disease. Additionally, Noted is an Additionally, Noted is an Echocardiogram Demonstrating Highly Echocardiogram Demonstrating Highly Abnormal Left Atrial Walls.Abnormal Left Atrial Walls.

Causes of Lymphocytic Pleural Causes of Lymphocytic Pleural EffusionsEffusions

CHF (Only Transudate)CHF (Only Transudate) NeoplasmNeoplasm Fungal InfectionFungal Infection TBTB SarcoidosisSarcoidosis Rheumatoid ArthritisRheumatoid Arthritis Hepatic HydrothoraxHepatic Hydrothorax Yellow Nail SyndromeYellow Nail Syndrome ChylothoraxChylothorax

Causes of Left Atrial Causes of Left Atrial EnlargementEnlargement

Valvular DiseaseValvular Disease Myocardial InfarctionMyocardial Infarction Obstructive CardiomyopathyObstructive Cardiomyopathy HypertensionHypertension Infiltrative CardiomyopathyInfiltrative Cardiomyopathy Inflammatory CardiomyopathyInflammatory Cardiomyopathy Primary or Metastatic TumorsPrimary or Metastatic Tumors

Differential Diagnosis for Differential Diagnosis for Pericardial EffusionPericardial Effusion

InfectiousInfectious MalignantMalignant AutoimmuneAutoimmune CardiomyopathyCardiomyopathy Drug InducedDrug Induced CardiacCardiac Constrictive Constrictive

PericarditisPericarditis

RadiationRadiation TraumaTrauma Metabolic: Metabolic:

Hypothyroidism Hypothyroidism Uremia Uremia Ovarian- Ovarian- Hyperstimulation- Hyperstimulation- SyndromeSyndrome

Pericardial EffusionPericardial Effusion All Causes of Pericardial Effusion Can All Causes of Pericardial Effusion Can

Also Cause Pleural Effusions.Also Cause Pleural Effusions.

All Causes of Pericardial Disease Can All Causes of Pericardial Disease Can Also Include the Myocardium to Varying Also Include the Myocardium to Varying Degrees. Termed Myopericarditis or Degrees. Termed Myopericarditis or Perimyocarditis.Perimyocarditis.

InfectiousInfectiousPericardial EffusionPericardial Effusion

ViralViral Pyogenic/BacterialPyogenic/Bacterial FungalFungal ParasiticParasitic TuberculousTuberculous Any Infectious Agent Can Affect the Any Infectious Agent Can Affect the

PericardiumPericardium

Viral PericarditisViral Pericarditis Most Common Infectious PericarditisMost Common Infectious Pericarditis Usually Cause Acute Pericarditis with: Fever, Rub, Typical Usually Cause Acute Pericarditis with: Fever, Rub, Typical

ECG Changes, Leukocytosis, ECG Changes, Leukocytosis, 3:1 Male to Female Ratio, Predominately in Young Adults3:1 Male to Female Ratio, Predominately in Young Adults Usually Self Limited Resolving Within 2 WeeksUsually Self Limited Resolving Within 2 Weeks Preceded by Upper Respiratory or GI Illness by 1-3 WeeksPreceded by Upper Respiratory or GI Illness by 1-3 Weeks 50% Have Recurrence Within 8 Months 50% Have Recurrence Within 8 Months Common Viruses: Enteroviruses, Coxsackie A&B, Common Viruses: Enteroviruses, Coxsackie A&B,

Adenovirus, Rhinovirus, Echovirus type 8, and InfluenzaAdenovirus, Rhinovirus, Echovirus type 8, and Influenza Diagnosis of ExclusionDiagnosis of Exclusion

Pyogenic/Bacterial PericarditisPyogenic/Bacterial Pericarditis Fulminant Course Fulminant Course Symptoms Arise Over a Few Days and Usually Lead to Symptoms Arise Over a Few Days and Usually Lead to

Tamponade and Sepsis Tamponade and Sepsis Commonly Pneumococus, Staph, StrepCommonly Pneumococus, Staph, Strep Typically Associated with High Fever (Virtually All Typically Associated with High Fever (Virtually All

Cases), Toxicity, Tachycardia, RubCases), Toxicity, Tachycardia, Rub Maybe More Insidious Course in the ElderlyMaybe More Insidious Course in the Elderly Usually Require Systemic Antibiotics and Pericardial Usually Require Systemic Antibiotics and Pericardial

Drainage With ExplorationDrainage With Exploration In the Antibiotic Era Usually Associated with Dialysis, In the Antibiotic Era Usually Associated with Dialysis,

Thoracic Surgery and Chemotherapy.Thoracic Surgery and Chemotherapy.

FungalFungal Pericarditis Pericarditis

Usually Occurs in ImmunocompromisedUsually Occurs in Immunocompromised Histoplasma: Usually Young Males in Endemic Histoplasma: Usually Young Males in Endemic

Areas, Often Benign Course Remitting Areas, Often Benign Course Remitting Spontaneously, May Have Mediastinal Spontaneously, May Have Mediastinal Lymphadnopathy and Pleural EffusionsLymphadnopathy and Pleural Effusions

Coccidiomycosis: Usually in Patients with Coccidiomycosis: Usually in Patients with Widely Disseminated InfectionWidely Disseminated Infection

Candida & Aspergillus: Opportunistic, Candida & Aspergillus: Opportunistic, Necrotizing and Leading to Thrombosis Necrotizing and Leading to Thrombosis

Parasitic PericarditisParasitic Pericarditis Clinical Course Resembles that of Clinical Course Resembles that of

Pyogenic PericarditisPyogenic Pericarditis Residents or Travelers to Endemic AreasResidents or Travelers to Endemic Areas Usually Have an Identifiable Primary Usually Have an Identifiable Primary

Source i.e. Liver or LungSource i.e. Liver or Lung EosinophilliaEosinophillia

Primary TumorsPrimary Tumors 75% Benign, 50% of Benign Tumors Are 75% Benign, 50% of Benign Tumors Are

MyxomasMyxomas

25% Malignant 25% Malignant 95% of Malignant Tumors Are Sarcomas95% of Malignant Tumors Are Sarcomas 5% of Malignant Tumors Are Lymphomas5% of Malignant Tumors Are Lymphomas Symptoms Related to Location and SizeSymptoms Related to Location and Size The Pathology of the Tumor Can Be Speculated The Pathology of the Tumor Can Be Speculated

by Appearance on Imaging and Anatomic by Appearance on Imaging and Anatomic LocationLocation

MyxomasMyxomas Occur in 3Occur in 3rdrd-6-6thth Decades Decades Female Predominance 60-70%Female Predominance 60-70% 80% Found in the Left Atrium80% Found in the Left Atrium Presentation: Obstruction of Mitral or Tricuspid Presentation: Obstruction of Mitral or Tricuspid

Valve 67% (Occasionally Positional), Embolization Valve 67% (Occasionally Positional), Embolization 29%, 15% of Cases Have Audible Tumor Plop29%, 15% of Cases Have Audible Tumor Plop

Constitutional Symptoms: Fever, Fatigue, Weight Constitutional Symptoms: Fever, Fatigue, Weight Loss, Myalgias, and ArthralgiasLoss, Myalgias, and Arthralgias

Not Commonly Associated With Pericardial Not Commonly Associated With Pericardial EffusionEffusion

MyxomasMyxomas Echo Demonstrates Endocardial Mass, Echo Demonstrates Endocardial Mass,

Rarely May Be IntramuralRarely May Be Intramural Treatment is Surgical Resection, Though Treatment is Surgical Resection, Though

Myxoma May Recur 1-5% Myxoma May Recur 1-5% 10% May Be Familial 10% May Be Familial

Benign Papillary Benign Papillary FibroelastomasFibroelastomas

22ndnd Most Common Benign Tumor Most Common Benign Tumor Predominantly Affect Valves, Account for Predominantly Affect Valves, Account for

75% of Valvular Tumors75% of Valvular Tumors Often Asymptomatic, But May Present Often Asymptomatic, But May Present

with Dyspnea, Embolization, or Chest with Dyspnea, Embolization, or Chest PainPain

Visible By Echo as Mobile Endocardial Visible By Echo as Mobile Endocardial MassMass

Other Benign Cardiac TumorsOther Benign Cardiac Tumors All Are RareAll Are Rare Rhabdomyomas: Most Present in ChildhoodRhabdomyomas: Most Present in Childhood Fibromas: Most Present in ChildhoodFibromas: Most Present in Childhood Hemangiomas: Have Characteristic Findings Hemangiomas: Have Characteristic Findings

on Imagingon Imaging Lipomas: Have Characteristic Findings on Lipomas: Have Characteristic Findings on

ImagingImaging Teratomas: Have Characteristic Findings on Teratomas: Have Characteristic Findings on

Imaging, Most Present in ChildhoodImaging, Most Present in Childhood

Malignant SarcomasMalignant Sarcomas Angiosarcomas: Most “Common” Angiosarcomas: Most “Common”

Malignant Primary Cardiac TumorMalignant Primary Cardiac Tumor Men:Women 3:1, 65-90% Have Men:Women 3:1, 65-90% Have

Metastases at PresentationMetastases at Presentation 80% Occur In the Right Atrium 80% Occur In the Right Atrium

(Other Sarcomas Are Usually in the (Other Sarcomas Are Usually in the Left Atrium)Left Atrium)

Malignant SarcomasMalignant Sarcomas Rhabdomyosarcoma: 2Rhabdomyosarcoma: 2ndnd Most Most

“Common” Malignant Primary Cardiac “Common” Malignant Primary Cardiac TumorTumor

Can Occur at Any AgeCan Occur at Any Age Most Have Aggressive Features Seen on Most Have Aggressive Features Seen on

Imaging (Invasion of Local Structures) Imaging (Invasion of Local Structures)

Primary Cardiac LymphomasPrimary Cardiac Lymphomas By Far Most Commonly Occur in the By Far Most Commonly Occur in the

Right AtriumRight Atrium More Common in AIDS and More Common in AIDS and

Immunocompromised PatientsImmunocompromised Patients Most Are Fatal Shortly After DiagnosisMost Are Fatal Shortly After Diagnosis

Metastatic TumorsMetastatic Tumors 20 Times More Common than Primary Tumors20 Times More Common than Primary Tumors Lung, Breast, Leukemia, Lymphoma, Melanoma, Lung, Breast, Leukemia, Lymphoma, Melanoma,

Kaposi’s SarcomaKaposi’s Sarcoma Presenting Symptoms Based on Location of Presenting Symptoms Based on Location of

Tumor, Usually Causes Pericardial EffusionTumor, Usually Causes Pericardial Effusion If the Patient Is Symptomatic the Tumor Is If the Patient Is Symptomatic the Tumor Is

Virtually Always Visible on Echo, CT or MRI Virtually Always Visible on Echo, CT or MRI Most Patients Have Mediastinal LymphadnopathyMost Patients Have Mediastinal Lymphadnopathy Most Have Aggressive Features Seen on Imaging Most Have Aggressive Features Seen on Imaging

(Invasion of Local Structures)(Invasion of Local Structures)

AutoimmuneAutoimmunePericardial EffusionPericardial Effusion

Rheumatoid ArthritisRheumatoid Arthritis SLESLE SclerodermaScleroderma Rheumatic FeverRheumatic Fever Wegener’s GranulomatosisWegener’s Granulomatosis Ankylosing SpondylitisAnkylosing Spondylitis Inflammatory Bowel DiseaseInflammatory Bowel Disease

CardiomyopathiesCardiomyopathies IschemicIschemic DilatedDilated HypertrophicHypertrophic ValvularValvular HypertensiveHypertensive Restrictive or InfiltrativeRestrictive or Infiltrative InflammatoryInflammatory

RestrictiveRestrictiveCardiomyopathyCardiomyopathy

Excessively Rigid Ventricular Walls Excessively Rigid Ventricular Walls Cause Diastolic DysfunctionCause Diastolic Dysfunction

Systolic Function Is Not ImpairedSystolic Function Is Not Impaired Commonly Present with Dyspnea, Commonly Present with Dyspnea,

Fatigue and Chest PainFatigue and Chest Pain Commonly Associated with A-FibCommonly Associated with A-Fib Difficult to Distinguish Clinically from Difficult to Distinguish Clinically from

Constrictive PericarditisConstrictive Pericarditis

RestrictiveRestrictiveCardiomyopathyCardiomyopathy

Storage Diseases Storage Diseases InfiltrativeInfiltrative EndomyocardialEndomyocardial

Restrictive CardiomyopathyRestrictive CardiomyopathyInherited Storage DisordersInherited Storage Disorders

Hemochromatosis: Deposition of Iron in Liver, Hemochromatosis: Deposition of Iron in Liver, Pancreas, Gonads and MyocardiumPancreas, Gonads and Myocardium

Fabry: Intracellular Accumulation of Fabry: Intracellular Accumulation of Glycosphingolipids in the Skin, Kidneys and Glycosphingolipids in the Skin, Kidneys and MyocardiumMyocardium

Gaucher: Accumulation of Cerebrosides in the Spleen, Gaucher: Accumulation of Cerebrosides in the Spleen, Liver, Bone Marrow, Lymph Nodes, Brain and Liver, Bone Marrow, Lymph Nodes, Brain and MyocardiumMyocardium

Glycogen Storage Diseases: Survival to Adulthood Glycogen Storage Diseases: Survival to Adulthood Uncommon Except in Type III, Where Infiltration of the Uncommon Except in Type III, Where Infiltration of the Myocardium is Usually Not Clinically RelevantMyocardium is Usually Not Clinically Relevant

Restrictive CardiomyopathyRestrictive CardiomyopathyInfiltrative DisordersInfiltrative Disorders

AmyloidAmyloid SarcoidSarcoid Carcinoid Heart Disease: Serotonin Carcinoid Heart Disease: Serotonin

Producing Tumor Causing Producing Tumor Causing Cutaneous Flushing, Diarrhea, Cutaneous Flushing, Diarrhea, Bronchoconstriction and Right Bronchoconstriction and Right Sided Endocardial Plaques Sided Endocardial Plaques Composed of Fibrous Tissue Composed of Fibrous Tissue

Restrictive Cardiomyopathy Restrictive Cardiomyopathy Endocardial Fibrotic DiseasesEndocardial Fibrotic Diseases

Endomyocardial Disease (Africa, Endomyocardial Disease (Africa, Eosinophilia)Eosinophilia)

Loffler Endocarditis (Eosinophilia)Loffler Endocarditis (Eosinophilia) Endomyocardial Fibrosis (Africa)Endomyocardial Fibrosis (Africa)

MyocarditisMyocarditis Primary Primary LymphocyticLymphocytic Acute Rheumatic FeverAcute Rheumatic Fever Eosinophilic Eosinophilic LymeLyme ChagasChagas HIVHIV Drugs Drugs RadiationRadiation Giant Cell Giant Cell

MyocarditisMyocarditis Inflammation of the Myocardium Associated with Inflammation of the Myocardium Associated with

Injury to MyocytesInjury to Myocytes Presents as an Acute Illness, Often Congestive Heart Presents as an Acute Illness, Often Congestive Heart

Failure, Chest Pain and FatigueFailure, Chest Pain and Fatigue Moderate Elevation of Cardiac Biomarkers, Moderate Elevation of Cardiac Biomarkers,

Nonspecific ST-T Changes, Arrhythmias, Nonspecific Nonspecific ST-T Changes, Arrhythmias, Nonspecific EchoEcho

Diagnosis by Endomyocardial BiopsyDiagnosis by Endomyocardial Biopsy

MyocarditisMyocarditis Primary or Acute Myocarditis Associated with Primary or Acute Myocarditis Associated with

Viral Infection (20 Viruses). Most Commonly Viral Infection (20 Viruses). Most Commonly Enteroviruses (Coxsackie). Viral Etiology Enteroviruses (Coxsackie). Viral Etiology Suggested by Antecedent Upper Respiratory Suggested by Antecedent Upper Respiratory or GI Illness. or GI Illness.

Acute Viral Myocarditis is Associated with Acute Viral Myocarditis is Associated with Lymphocytic InfiltrateLymphocytic Infiltrate

Inflammatory MyocarditisInflammatory Myocarditis Lymphocytic Myocarditis: Most Will Improve Over 1-6 Lymphocytic Myocarditis: Most Will Improve Over 1-6

Months, a Minority Will Fail to Clear a Cardiotropic Virus Months, a Minority Will Fail to Clear a Cardiotropic Virus or Develop Persistent Inflammation That Leads to or Develop Persistent Inflammation That Leads to Chronic Cardiomyopathy, Heart Block or Ventricular Chronic Cardiomyopathy, Heart Block or Ventricular Arrhythmias. Arrhythmias.

Myocarditis Treatment Trial: Prospective Randomized, Myocarditis Treatment Trial: Prospective Randomized, Double-Blind, Placebo-Controlled Trial of Prednisone and Double-Blind, Placebo-Controlled Trial of Prednisone and Cyclosporine or Azathioprine for the Treatment of Biopsy Cyclosporine or Azathioprine for the Treatment of Biopsy Proven Lymphocytic Myocarditis in Acute CHF. There Proven Lymphocytic Myocarditis in Acute CHF. There Was No Benefit from Immunosuppression.Was No Benefit from Immunosuppression.

Immune Modulation for Acute Cardiomyopathy: Immune Modulation for Acute Cardiomyopathy: Evaluated the Role of IVIG and Found no Benefit.Evaluated the Role of IVIG and Found no Benefit.

May Lead to Dilated CardiomyopathyMay Lead to Dilated Cardiomyopathy

Inflammatory MyocarditisInflammatory Myocarditis Acute Rheumatic Fever: Pancarditis Occurring in 3% of Acute Rheumatic Fever: Pancarditis Occurring in 3% of

Untreated Streptococal A Pharyngeal InfectionsUntreated Streptococal A Pharyngeal Infections Hypersensitivity Myocarditis (Drug Induced): Tricyclics, Hypersensitivity Myocarditis (Drug Induced): Tricyclics,

Penicillins, Antipsychotics, Present with Rash & FeverPenicillins, Antipsychotics, Present with Rash & Fever Eosinophilic Myocarditis: Occurs in Conjunction with: Eosinophilic Myocarditis: Occurs in Conjunction with:

Hypereosinophilic Syndrome, Churg-Strauss Syndrome & Hypereosinophilic Syndrome, Churg-Strauss Syndrome & Loffler’s Endomyocardial Fibrosis. Peripheral EosinophiliaLoffler’s Endomyocardial Fibrosis. Peripheral Eosinophilia

Lyme Myocarditis: Borrelia burgdorferi, Often Develop Lyme Myocarditis: Borrelia burgdorferi, Often Develop Heart Block or Arrhythmias,Heart Block or Arrhythmias,

Chagas Cardiomyopathy: Trypanosoma cruzi (Protozoan), Chagas Cardiomyopathy: Trypanosoma cruzi (Protozoan), Endemic to Central & South AmericaEndemic to Central & South America

HIV MyocarditisHIV Myocarditis

Drug Induced Pericardial Drug Induced Pericardial EffusionEffusion

ProcainamideProcainamide HydralazineHydralazine Phenytoin Phenytoin IsoniazideIsoniazide MinoxidilMinoxidil Methysergide\ Methysergide\

ergot derivativeergot derivative Phenylbutazone/ Phenylbutazone/

NSAIDNSAID

AnticoagulantsAnticoagulants Cromolyn SodiumCromolyn Sodium DantroleneDantrolene ThromboticsThrombotics PenicillinPenicillin Doxorubicin/ Doxorubicin/

AdriamycinAdriamycin Cytoxan/ Cytoxan/

CyclophosphamideCyclophosphamide

CardiacCardiacPericardial EffusionsPericardial Effusions

Myocardial InfarctionMyocardial Infarction Postmyocardial Infarction “Dressler’s Postmyocardial Infarction “Dressler’s

Syndrome”Syndrome” TraumaTrauma Aortic Dissection with Hemorrhage into Aortic Dissection with Hemorrhage into

Pericardial SpacePericardial Space PostpericardiotomyPostpericardiotomy

Constrictive PericarditisConstrictive Pericarditis No Pericardial Thickening Was Noted on No Pericardial Thickening Was Noted on

ImagingImaging Few Case Reports of Constriction Few Case Reports of Constriction

Without Pericardial Thickening Without Pericardial Thickening Would Not Account for Abnormal Left Would Not Account for Abnormal Left

Atrium Seen on EchoAtrium Seen on Echo

Possible Etiologies for This Possible Etiologies for This CaseCase

Tuberculous PericarditisTuberculous Pericarditis Cardiac SarcoidosisCardiac Sarcoidosis Cardiac AmyloidosisCardiac Amyloidosis Giant Cell MyocarditisGiant Cell Myocarditis

Tuberculous PericarditisTuberculous Pericarditis 4-10% of All Acute Pericarditis is Caused 4-10% of All Acute Pericarditis is Caused

by TB (Reported up to 80% in Some 3by TB (Reported up to 80% in Some 3rdrd World Countries) World Countries)

1-4% of Patients with TB Have Pericardial 1-4% of Patients with TB Have Pericardial InvolvementInvolvement

Etiology of 20% of Constrictive Etiology of 20% of Constrictive PericarditisPericarditis

Cases 93% of all Pericardial Effusions in Cases 93% of all Pericardial Effusions in HIV PatientsHIV Patients

Four Pathologic Stages of TB Four Pathologic Stages of TB PericarditisPericarditis

I-Dry: Fibrin Deposition & Granulomatous I-Dry: Fibrin Deposition & Granulomatous Reaction. Usually Clinically Silent Reaction. Usually Clinically Silent

II-Effusive: Serous Fluid Accumulation Caused II-Effusive: Serous Fluid Accumulation Caused by Hypersensitivity to Tuberculoprotein and by Hypersensitivity to Tuberculoprotein and Impaired ResorptionImpaired Resorption

III- Absorptive: Effusion Resolves and Fibrous III- Absorptive: Effusion Resolves and Fibrous Tissue Replaces Granulomas, Pericardium Tissue Replaces Granulomas, Pericardium ThickensThickens

IV-Constrictive: Parietal Pericardial IV-Constrictive: Parietal Pericardial CalcificationCalcification

Presentation of Tuberculous Presentation of Tuberculous PericarditisPericarditis

Dyspnea 45-90%Dyspnea 45-90% Chest Pain 40-75%Chest Pain 40-75% Orthopnea 20-65%Orthopnea 20-65% Distant Heart Sounds Distant Heart Sounds

25-55%25-55%

Rub 30-85%Rub 30-85% Cough 50-95%Cough 50-95% Fever 80-100%Fever 80-100%

Presentation of Tuberculous Presentation of Tuberculous PericarditisPericarditis

50% of Patient Have Slowly Progressive 50% of Patient Have Slowly Progressive Insidious PresentationInsidious Presentation

95% Have Cardiomegally, 30% Have 95% Have Cardiomegally, 30% Have Active Pulmonary TB, 39-71% Have Active Pulmonary TB, 39-71% Have Pleural Effusions L>R. Bilateral Pleural Pleural Effusions L>R. Bilateral Pleural Effusions More Common than Rub.Effusions More Common than Rub.

Tuberculous PericarditisTuberculous Pericarditis ““Because of the variable and nonspecific Because of the variable and nonspecific

features of TB pericarditis, establishing features of TB pericarditis, establishing the diagnosis on clinical grounds alone the diagnosis on clinical grounds alone is impossible.” D.H. Spodickis impossible.” D.H. Spodick

Diagnosis by Pericardial Fluid or Biopsy: Diagnosis by Pericardial Fluid or Biopsy: Positive AFB Smear, Culture, Caseating Positive AFB Smear, Culture, Caseating Granulomas, TB DNA PCRGranulomas, TB DNA PCR

TreatmentTreatmentTuberculous PericarditisTuberculous Pericarditis

Antibiotics: Isoniazid, Rifampin, Antibiotics: Isoniazid, Rifampin, Pyrazinamide, EthambutolPyrazinamide, Ethambutol

Corticosteroids: Reduces Mortality and Corticosteroids: Reduces Mortality and Need for Subsequent PericardiocentisisNeed for Subsequent Pericardiocentisis

Cardiac SarcoidosisCardiac Sarcoidosis Causes Restrictive CardiomyopathyCauses Restrictive Cardiomyopathy Clinically Relevant in 5%, 25% Incidentally Clinically Relevant in 5%, 25% Incidentally

Noted at AutopsyNoted at Autopsy 69% of Clinically Relevant Cardiac Sarcoidosis 69% of Clinically Relevant Cardiac Sarcoidosis

Patients Have No Other Manifestations of the Patients Have No Other Manifestations of the Disease at PresentationDisease at Presentation

Presentation: Complete Heart Block (Be Presentation: Complete Heart Block (Be Suspicious in Young Patients With Complete Suspicious in Young Patients With Complete Heart Block), Ventricular Arrhythmia, Heart Block), Ventricular Arrhythmia, Congestive Heart Failure Systolic or Diastolic Congestive Heart Failure Systolic or Diastolic DysfunctionDysfunction

Cardiac SarcoidosisCardiac Sarcoidosis Echo Usually Reveals Hyperechogenic Left Echo Usually Reveals Hyperechogenic Left

Ventricular Walls, May Develop Ventricular Ventricular Walls, May Develop Ventricular Aneurysm From Myocardial Scar TissueAneurysm From Myocardial Scar Tissue

Diagnosis Based on Clinical Suspicion in a Diagnosis Based on Clinical Suspicion in a Patient with Known Sarcoid or by Patient with Known Sarcoid or by Endomyocardial Biopsy in a Patient with No Endomyocardial Biopsy in a Patient with No Evidence of Sarcoid in Other Organs. Biopsy Evidence of Sarcoid in Other Organs. Biopsy Consistent with Sarcoid 30% of Cases.Consistent with Sarcoid 30% of Cases.

Treat with SteroidsTreat with Steroids

Cardiac AmyloidosisCardiac Amyloidosis Causes Restrictive CardiomyopathyCauses Restrictive Cardiomyopathy Myocyte Destruction and Replacement Myocyte Destruction and Replacement

with Amyloid Fibrils (Beta Pleated with Amyloid Fibrils (Beta Pleated Sheets) Leading to Progressive Sheets) Leading to Progressive Thickening of the Ventricular Walls.Thickening of the Ventricular Walls.

More Common in Primary (AL) More Common in Primary (AL) Amyloidosis, a Plasma Cell Dyscrasia Amyloidosis, a Plasma Cell Dyscrasia Where Immunoglobulins Form Amyloid Where Immunoglobulins Form Amyloid ProteinProtein

Cardiac AmyloidosisCardiac Amyloidosis EKG: Often Have Bundle Branch Block, Low EKG: Often Have Bundle Branch Block, Low

Voltage Despite Thick Ventricles, or A-Fib Voltage Despite Thick Ventricles, or A-Fib Most Patients with Amyloidosis, Even Those Most Patients with Amyloidosis, Even Those

with no Cardiac Symptoms, Have Abnormal with no Cardiac Symptoms, Have Abnormal Echocardiograms with: Ventricular Wall Echocardiograms with: Ventricular Wall Thickening (70%), Isolated Septal Wall Thickening (70%), Isolated Septal Wall Thickening (30%), Diastolic Dysfunction (57%), Thickening (30%), Diastolic Dysfunction (57%), Systolic Dysfunction (27%), Pericardial Systolic Dysfunction (27%), Pericardial Effusion (40%), Myocardial Sparkling Pattern in Effusion (40%), Myocardial Sparkling Pattern in 2D (27%)2D (27%)

Cardiac AmyloidosisCardiac Amyloidosis Diagnosis with Tissue Biopsy Revealing Diagnosis with Tissue Biopsy Revealing

Amyloidosis, Often Abdominal Fat PadAmyloidosis, Often Abdominal Fat Pad Prognosis Less Than 1 Year, Survival at Prognosis Less Than 1 Year, Survival at

5 Years <5% 5 Years <5% Treatment: Primary Amyliodosis Limited Treatment: Primary Amyliodosis Limited

Benefit of Alkylating AgentsBenefit of Alkylating Agents Secondary Amyloidosis: Treat Secondary Amyloidosis: Treat

Underlying DiseaseUnderlying Disease

Giant Cell MyocarditisGiant Cell Myocarditis Causes Inflammatory CardiomyopathyCauses Inflammatory Cardiomyopathy Unknown Etiology Unknown Etiology Causes Progressive Left Ventricular Failure Causes Progressive Left Ventricular Failure

and Arrhythmias, Over Weeks to Monthsand Arrhythmias, Over Weeks to Months Rare, 80 Cases Reported by 1997 Rare, 80 Cases Reported by 1997 Average Age 43 (Infants to Elderly) Usually Average Age 43 (Infants to Elderly) Usually

Affects Otherwise Healthy PatientsAffects Otherwise Healthy Patients Equal Predominance of Men and WomenEqual Predominance of Men and Women 90% Are Caucasian90% Are Caucasian

Giant Cell MyocarditisGiant Cell Myocarditis Diagnosed by Endomyocardial Biopsy Diagnosed by Endomyocardial Biopsy

Demonstrating: Diffuse Myocardial Demonstrating: Diffuse Myocardial Necrosis with Multinucleated Giant Cells Necrosis with Multinucleated Giant Cells in the Absence of Sarcoid Like in the Absence of Sarcoid Like Granuloma. Inflammatory Infiltrate in Granuloma. Inflammatory Infiltrate in Close Apposition to Myocyte Necrosis. Close Apposition to Myocyte Necrosis. Negative Culture and Stains for Infection, Negative Culture and Stains for Infection, No Viral Particles on Electron No Viral Particles on Electron Microscopy.Microscopy.

Giant Cell MyocarditisGiant Cell Myocarditis 75% Present with CHF, 25% with Ventricular 75% Present with CHF, 25% with Ventricular

Arrhythmias, Sudden Cardiac Death (50%), Heart Arrhythmias, Sudden Cardiac Death (50%), Heart Block, Diffuse ST-T Abnormalities on EKG.Block, Diffuse ST-T Abnormalities on EKG.

May be Localized Rather Than Diffuse in Earlier May be Localized Rather Than Diffuse in Earlier Stages. There Are Case Reports of Giant Cell Stages. There Are Case Reports of Giant Cell Myocarditis Affecting Only the Atria. Myocarditis Affecting Only the Atria.

20% Have Other Autoimmune Disease: Hashimoto 20% Have Other Autoimmune Disease: Hashimoto Thyroiditis, RA, MG, Takayasu Arteritis, Alopecia, Thyroiditis, RA, MG, Takayasu Arteritis, Alopecia, Vitiligo, Pernicious Anemia, Crohn’s Disease, Vitiligo, Pernicious Anemia, Crohn’s Disease, Ulcerative Colitis, ITP, Celiac DiseaseUlcerative Colitis, ITP, Celiac Disease

Giant Cell MyocarditisGiant Cell Myocarditis Survival 5.5 Months After Onset of Symptoms, Survival 5.5 Months After Onset of Symptoms,

Normally Succumb to CHF or Arrhythmia Normally Succumb to CHF or Arrhythmia Immunosuppresive Therapy with Corticosteroids, Immunosuppresive Therapy with Corticosteroids,

Cyclosporin, Azathioprine Increases Survival to 12 Cyclosporin, Azathioprine Increases Survival to 12 Months, Case Reports of Dramatic Improvement with Months, Case Reports of Dramatic Improvement with ImmunotherapyImmunotherapy

Cardiac Transplantation (with 25% recurrence), 71% Cardiac Transplantation (with 25% recurrence), 71% Survival at 5 Years Survival at 5 Years

The Giant Cell Myocarditis Treatment Trial and The Giant Cell Myocarditis Treatment Trial and Registry, Randomized Controlled Trial of T-Cell Registry, Randomized Controlled Trial of T-Cell Targeted Treatment with Muromonab-CD3 and Targeted Treatment with Muromonab-CD3 and CyclosporineCyclosporine

Possible Etiologies for This CasePossible Etiologies for This Case Tuberculous PericarditisTuberculous Pericarditis No Fever, No Exposure, Not Immunocompromized, No Fever, No Exposure, Not Immunocompromized,

Would Not Explain Abnormal AtriumWould Not Explain Abnormal Atrium Cardiac SarcoidosisCardiac Sarcoidosis No Evidence of Systemic Sarcoid, Normal Left No Evidence of Systemic Sarcoid, Normal Left

Ventricular WallsVentricular Walls Cardiac AmyloidosisCardiac Amyloidosis No Low Voltage EKG, No Ventricular Wall ThickeningNo Low Voltage EKG, No Ventricular Wall Thickening Giant Cell MyocarditisGiant Cell Myocarditis Time Course Is Consistant with Our Patient, Could Time Course Is Consistant with Our Patient, Could

Account for Symptoms of CHF, Effusions, and Account for Symptoms of CHF, Effusions, and Abnormal Left AtriumAbnormal Left Atrium

DiagnosisDiagnosis

Giant Cell MyocarditisGiant Cell Myocarditis

Diagnostic Test of Choice: Diagnostic Test of Choice: Endomyocardial Biopsy Endomyocardial Biopsy

ReferencesReferences Spodick DH. The Pericardium. New York: Marcel Dekker; 1997Spodick DH. The Pericardium. New York: Marcel Dekker; 1997 Braunwald E, Fauci AS. Harrison’s Textbook of Internal Medicine. McGraw-Hill; 2001Braunwald E, Fauci AS. Harrison’s Textbook of Internal Medicine. McGraw-Hill; 2001 Up To Date, 2007Up To Date, 2007 Garay S, Rom WN. Tuberculosis. Boston: Libble, Brown & CO; 1996Garay S, Rom WN. Tuberculosis. Boston: Libble, Brown & CO; 1996 Hall HD, Hammar SP. Pulmonary Pathology. New York: Springer-Verlag; 1994Hall HD, Hammar SP. Pulmonary Pathology. New York: Springer-Verlag; 1994 Roth JA, Ruckdeschel JC. Weisenburger, T. H. Thoracic Oncology. Philadelphia: W.B. Roth JA, Ruckdeschel JC. Weisenburger, T. H. Thoracic Oncology. Philadelphia: W.B.

Saunders Company; 1995Saunders Company; 1995 Murphy JG, Lloyd MA. Mayo Clinic Cardiology. Rochester: Mayo Clinic Scientific Press; 2007Murphy JG, Lloyd MA. Mayo Clinic Cardiology. Rochester: Mayo Clinic Scientific Press; 2007 Zipes DP, Libby P, Bonow RO, Braunwald E. Braunwald’s Heart Disease. Philadelphia: Zipes DP, Libby P, Bonow RO, Braunwald E. Braunwald’s Heart Disease. Philadelphia:

Elsevier Saunders; 2005Elsevier Saunders; 2005 Silver MD, Gotlieb AI, Schoen FJ. Cardiovascular Pathology. Philadelphia: Churchill Silver MD, Gotlieb AI, Schoen FJ. Cardiovascular Pathology. Philadelphia: Churchill

Livingstone; 2001Livingstone; 2001 Cooper LT, Berry GJ, et al: Idiopathic Giant-Cell Myocarditis. NE J Medicine, June, 1997Cooper LT, Berry GJ, et al: Idiopathic Giant-Cell Myocarditis. NE J Medicine, June, 1997 Frustaci A, Chimenti C, et al: Giant Cell Myocarditis, Responding to Immunosuppressive Frustaci A, Chimenti C, et al: Giant Cell Myocarditis, Responding to Immunosuppressive

Therapy. Chest, March, 2000Therapy. Chest, March, 2000 Cooper LT: Giant Cell Myocarditis: Diagnosis and Treatment. Herz, May, 2000Cooper LT: Giant Cell Myocarditis: Diagnosis and Treatment. Herz, May, 2000 Rosenstein ED, Zucker MJ, et al: Giant Cell Myocarditis: Most Fatal of Autoimmune Diseases. Rosenstein ED, Zucker MJ, et al: Giant Cell Myocarditis: Most Fatal of Autoimmune Diseases.

Seminars in Arthrithritis and Rheumatism, August, 2000Seminars in Arthrithritis and Rheumatism, August, 2000

Special Thanks To:Special Thanks To:

Dr. ErwinDr. Erwin Dr. StarrDr. Starr Dr. HurleyDr. Hurley