““Doc, I think I’ve got Doc, I think I’ve got ______”______”

A walk-in physician-patient with a A walk-in physician-patient with a coughcough

CC: Persistent CoughCC: Persistent Cough

57 year-old physician walked in asking to be 57 year-old physician walked in asking to be seen for 3 weeks of URI symptoms—new ptseen for 3 weeks of URI symptoms—new pt

HA, cough, aches, pains, low grade tempHA, cough, aches, pains, low grade temp ““Doc, I thought I had attenuated influenza”Doc, I thought I had attenuated influenza” Better in two days, but 1 week later: Better in two days, but 1 week later:

Localized R upper chest pain, rhinorrheaLocalized R upper chest pain, rhinorrhea

““Doc, I thought I had RUL pneumonia”Doc, I thought I had RUL pneumonia” Now with persistent cough…” Doc, I’ve got Now with persistent cough…” Doc, I’ve got

Pertussis”Pertussis”

Past Medical HistoryPast Medical History

Has never seen a doctorHas never seen a doctor No health maintenanceNo health maintenance Meds: noneMeds: none FHx: not elicitedFHx: not elicited SHx: no stress—only doc in clinic for SHx: no stress—only doc in clinic for

the next 6 days b/o conferencethe next 6 days b/o conference No cigarettes, no etoh, no social/street No cigarettes, no etoh, no social/street

drug usedrug use

Physical ExamPhysical Exam VS: Bp 170/106, P=84,RR=14, T=97.9VS: Bp 170/106, P=84,RR=14, T=97.9 Very comfortable, not illVery comfortable, not ill ENT: clear TMs, post pharynx nl, ENT: clear TMs, post pharynx nl, Large bi-lobed anterior cervical mass, Large bi-lobed anterior cervical mass,

3cm x2cmx3cm, soft, well circumscribed, movable, non 3cm x2cmx3cm, soft, well circumscribed, movable, non tendertender

No other adenopathyNo other adenopathy Cor: examined upright, no murmurCor: examined upright, no murmur Lungs: clearLungs: clear Abdomen: benign, Abdomen: benign, Ext/joints/skin: negativeExt/joints/skin: negative Normal pulse oximetryNormal pulse oximetry

Assessment and Plan: Assessment and Plan: 1)URI 2) untreated HTN 3) neck mass1)URI 2) untreated HTN 3) neck mass

R/O Pertussis R/O Pertussis Rx: Azithromycin for persistent symptomsRx: Azithromycin for persistent symptoms Start assessment and treatment of Start assessment and treatment of

hypertensionhypertension Evaluate R Neck mass later: ?MRI, FNA?Evaluate R Neck mass later: ?MRI, FNA? Health Maintenance and wellness care: Health Maintenance and wellness care:

colonoscopy , prostate exam, diet, sodium colonoscopy , prostate exam, diet, sodium restriction, exercise, and weight loss restriction, exercise, and weight loss prescriptionprescription

Work up: that dayWork up: that day

ECG: orderedECG: ordered CXR: orderedCXR: ordered

F/U: “1-2 weeks depending on how you do; F/U: “1-2 weeks depending on how you do; off work till pertussis cx back; call me off work till pertussis cx back; call me anytime”anytime”

Later: Labs: WBC: 9,900, 76% PMNs; Later: Labs: WBC: 9,900, 76% PMNs; crit=45%, platelets nl, ESR=16, Lytes, Bun nl, crit=45%, platelets nl, ESR=16, Lytes, Bun nl, Cr=1.1, Calcium=8.2, nl LFTs, LDL-118, Cr=1.1, Calcium=8.2, nl LFTs, LDL-118, HDL=34, TG=85, TSH=0.76, U/A 2-5 RBCsHDL=34, TG=85, TSH=0.76, U/A 2-5 RBCs

Six days later…Six days later…

Patient stopped me in the parking lot Patient stopped me in the parking lot on the way to clinic that am, leaned out on the way to clinic that am, leaned out of his car window and said,of his car window and said,

““Doc, I think I’ve got ____________”Doc, I think I’ve got ____________”

No better, except cough decreasedNo better, except cough decreased CC: Fever, night sweats, easy fatigueCC: Fever, night sweats, easy fatigue Pertussis PCR negative from 4/27Pertussis PCR negative from 4/27

More history, a second ROSMore history, a second ROS

““I forgot to tell you that I have MVP, found I forgot to tell you that I have MVP, found out in medical school” and…out in medical school” and…

““I was told I had hypertension years ago”I was told I had hypertension years ago” “ “I skied at high altitude in January”I skied at high altitude in January” ““I saw the dentist three times in March and I saw the dentist three times in March and

forgot my SBE prophylaxis each time”forgot my SBE prophylaxis each time” No ENT complaints, no SOB, palpitations, No ENT complaints, no SOB, palpitations,

CP; no GI, GU, joint or skin sx, no CP; no GI, GU, joint or skin sx, no neurological complaintsneurological complaints

Repeat Physical Exam Repeat Physical Exam

VS: BP=160/95, T=101.1, P=120 and regularVS: BP=160/95, T=101.1, P=120 and regular ENT=neg., no cotton wool exudatesENT=neg., no cotton wool exudates Cardiac: no murmur sitting, but loud, coarse Cardiac: no murmur sitting, but loud, coarse

holosystolic 3/6 murmur lying, no change holosystolic 3/6 murmur lying, no change with squatting and standing, no MSClick, no with squatting and standing, no MSClick, no S3 or S4S3 or S4

Lungs: clearLungs: clear Rest of exam benign: no peripheral stigmata Rest of exam benign: no peripheral stigmata

of his disease of his disease

New LabsNew Labs

WBC= 12,400; 88% PMNs, ESR=28WBC= 12,400; 88% PMNs, ESR=28 Urinalysis: neg.Urinalysis: neg. CXR: unchangedCXR: unchanged

3 sets of blood cultures obtained that day3 sets of blood cultures obtained that day Echocardiogram scheduled for next am—Echocardiogram scheduled for next am—

he had to work in clinic that dayhe had to work in clinic that day

Next DayNext Day Blood cultures by 8am next am: gram + cocci in Blood cultures by 8am next am: gram + cocci in

chainschains EchocardiogramEchocardiogram LA severely dilated, RV: nl size and fn;LA severely dilated, RV: nl size and fn; Left Ventricle: severely dilated, nl fn, EF=60%, Left Ventricle: severely dilated, nl fn, EF=60%,

eccentric hypertrophy due to chamber enlargement; eccentric hypertrophy due to chamber enlargement; Mitral Valve: Severe late systolic prolapse with Mitral Valve: Severe late systolic prolapse with

ant and post leaflets, P2 flail, severe valve ant and post leaflets, P2 flail, severe valve regurgitationregurgitation

Systemic veins: blunted vena cava changes c/w Systemic veins: blunted vena cava changes c/w increased CVPincreased CVP

Small pericardial effusion not hemodynamically Small pericardial effusion not hemodynamically significantsignificant

The patient was admitted The patient was admitted

Infective EndocarditisInfective EndocarditisObjectivesObjectives

Discuss briefly the epidemiology of Discuss briefly the epidemiology of Infective Endocarditis (IE): Risk factors, Infective Endocarditis (IE): Risk factors, Diagnosis, and TreatmentDiagnosis, and Treatment

Focus on native valve infections, MVPFocus on native valve infections, MVP Review Dental ProphylaxisReview Dental Prophylaxis Increase clinician’s level of suspicion Increase clinician’s level of suspicion

for early diagnosisfor early diagnosis Ending: physician-patients: The case of Ending: physician-patients: The case of

Alfred ReinhartAlfred Reinhart

Firschke C, Schomig A, N Engl J Med, 345(10):739

Epidemiology and Predisposing Epidemiology and Predisposing FeaturesFeatures

Incidence: 1.7-6.2 cases /100K person yearsIncidence: 1.7-6.2 cases /100K person years Risk Factors: IDU, prosthetic valves, structural heart Risk Factors: IDU, prosthetic valves, structural heart

disease (75%; mostly AS, MVP and VSD)disease (75%; mostly AS, MVP and VSD) Organisms: S. Aureus 32%, Viridans strep 18%Organisms: S. Aureus 32%, Viridans strep 18% New trends over past 30 yearsNew trends over past 30 years

Increasingly a disease of those >60Increasingly a disease of those >60 S aureus IE : hemodialysis dependent, diabetic, S aureus IE : hemodialysis dependent, diabetic,

intravascular device, s/p rx with vancomycin, MRSAintravascular device, s/p rx with vancomycin, MRSA More prosthetic valves, more nosocomial infectionsMore prosthetic valves, more nosocomial infections

MVP now most common predisposing cardiac MVP now most common predisposing cardiac condition; inc risk with MR , thickened leaflets*condition; inc risk with MR , thickened leaflets*

*NEJM 2001; 345(18):1318-*NEJM 2001; 345(18):1318-

Clinical ManifestationsClinical Manifestations

Fever: most common symptomFever: most common symptom Anorexia, weight loss, malaise, night sweats, Anorexia, weight loss, malaise, night sweats,

arthralgiasarthralgias Heart murmurHeart murmur Petechiae on skin, conjunctivaePetechiae on skin, conjunctivae SplenomegalySplenomegaly Osler’s nodes: Tender subcutaneous Osler’s nodes: Tender subcutaneous

nodules on pulp of fingersnodules on pulp of fingers Janeway lesions: nontender hemorrhagic/ Janeway lesions: nontender hemorrhagic/

pustular lesions on palms, solespustular lesions on palms, soles

Diagnosis:Diagnosis: Integration of clinical, lab and echo findingsIntegration of clinical, lab and echo findings

Nonspecific labs: anemia, leukocytosis, abnormal Nonspecific labs: anemia, leukocytosis, abnormal UA, elevated ESR and CRPUA, elevated ESR and CRP

Duke Criteria (1994)*Duke Criteria (1994)* Predisposing factors, Blood cx isolate, Predisposing factors, Blood cx isolate,

persistence of bacteremia, echo findingspersistence of bacteremia, echo findings• Specificity 0.99 negative predictive value >92%Specificity 0.99 negative predictive value >92%

Duke Criteria Expansion w/ TEE: more sensitive, Duke Criteria Expansion w/ TEE: more sensitive, better for smaller vegetations and perivalvular better for smaller vegetations and perivalvular vegetations: Negative predictive value: 92-100%**vegetations: Negative predictive value: 92-100%**

* Am J med 1994;9:200- **NEJM 2001;345(18):1322* Am J med 1994;9:200- **NEJM 2001;345(18):1322

Complications: CHF and Complications: CHF and Neurological EventsNeurological Events

EmbolicEmbolic 23-35% patients, encephalopathy, stroke, 23-35% patients, encephalopathy, stroke,

abscess, seizuresabscess, seizures Local spread of infection : heart valve Local spread of infection : heart valve

destructiondestruction HF most common cause of death, perivalvular HF most common cause of death, perivalvular

abscesses are noted in 30-40% at autopsyabscesses are noted in 30-40% at autopsy Think of abscess when fever persistsThink of abscess when fever persists

Metastatic infection: vertebral osteomyelitisMetastatic infection: vertebral osteomyelitis Immune mediated damage: Immune mediated damage:

glomerulonephritisglomerulonephritis

Musculoskeletal ComplicationsMusculoskeletal Complications

Acute septic arthritisAcute septic arthritis Axial skeletal infections( sacroiliac, Axial skeletal infections( sacroiliac,

pubic, sternal)pubic, sternal) Typical IE organisms grow from joint Typical IE organisms grow from joint

tap/ culturetap/ culture Multiple joints infectedMultiple joints infected

EmbolizationEmbolization StrokeStroke BlindnessBlindness Painful ischemic or gangrenous extremitiesPainful ischemic or gangrenous extremities Pain syndromes, splenic infarctionPain syndromes, splenic infarction HypoxiaHypoxia ParalysisParalysis Consider IE with systemic arterial Consider IE with systemic arterial

embolizationembolization Embolic events can occur weeks after Embolic events can occur weeks after

antibiotic therapyantibiotic therapy Usually related to large vegetations, S. Bovis Usually related to large vegetations, S. Bovis

and S. aureus, Left-sided vegetations, and S. aureus, Left-sided vegetations, antiphospholipid antibodiesantiphospholipid antibodies

MortalityMortality

Causative organismCausative organism 4-16% mortality from viridans streptococci4-16% mortality from viridans streptococci

Presence of complications or coexisting Presence of complications or coexisting conditionsconditions CHF, ARF, immmunosupression, neurologic CHF, ARF, immmunosupression, neurologic

eventsevents Development of perivalvular abscesses, Development of perivalvular abscesses, Use of combined medical and surgical Use of combined medical and surgical

therapytherapy Overall MORTALITY: 20-25%Overall MORTALITY: 20-25%

Theoretical Basis for Theoretical Basis for Antimicrobial ProphylaxisAntimicrobial Prophylaxis

Formation of a small noninfected Formation of a small noninfected thrombus on an abnormal endothelial thrombus on an abnormal endothelial surfacesurface

Secondary infection of this nidus with Secondary infection of this nidus with bacteria that are transiently circulatingbacteria that are transiently circulating

Proliferation of bacteria resulting in the Proliferation of bacteria resulting in the formation of vegetations on the formation of vegetations on the endothelial surfaceendothelial surface Durack, DT, Prevention of Infective Durack, DT, Prevention of Infective

Endocarditis NEJM 1995;332:38.Endocarditis NEJM 1995;332:38.

Biologic PlausibilityBiologic Plausibility

Animal studies: IE can be predictably induced if Animal studies: IE can be predictably induced if bacteria are injected into lab animals after heart bacteria are injected into lab animals after heart valves have been traumatized with catheters, valves have been traumatized with catheters, and prevented with timely use of antibioticsand prevented with timely use of antibiotics

Children (n=100) with endotracheal intubation, Children (n=100) with endotracheal intubation, and routine dental cleaning/ext had +BCand routine dental cleaning/ext had +BC 1.5 minutes p last extraction; +BC significantly less 1.5 minutes p last extraction; +BC significantly less

with amoxicillin ( 33 vs. 84 percent)with amoxicillin ( 33 vs. 84 percent)

• Antibacterial prophylaxis for dental, GI and GU procedures Antibacterial prophylaxis for dental, GI and GU procedures Medical Lett drugs Ther. 2005;47-59Medical Lett drugs Ther. 2005;47-59

IE and Antimicrobial ProphylaxisIE and Antimicrobial Prophylaxis

Standard, yet no prospective study has proven that such Standard, yet no prospective study has proven that such therapy is beneficialtherapy is beneficial

Cochrane(2004*): out of 980 studies, no RCTs, CCTs or Cochrane(2004*): out of 980 studies, no RCTs, CCTs or cohort studiescohort studies Netherlands: all cases for two years (n=24) paired with Netherlands: all cases for two years (n=24) paired with

controls in local cardiology clinics: No significant controls in local cardiology clinics: No significant effect of PCN prophylaxis on incidence of endocarditis effect of PCN prophylaxis on incidence of endocarditis could be seen, no data on other outcomescould be seen, no data on other outcomes

Malpractice claims and rewards for damages are commonMalpractice claims and rewards for damages are common—discuss with patients; informed consent necessary—discuss with patients; informed consent necessary

• *Oliver, et al Cochrane Database 2006;vol 1 [no pp #]*Oliver, et al Cochrane Database 2006;vol 1 [no pp #]

Medical Treatment of Native Medical Treatment of Native Valve EndocarditisValve Endocarditis

Prolonged iv administration of bacteriocidal Prolonged iv administration of bacteriocidal antibiotic or combination of agentsantibiotic or combination of agents Outpatient once fever has resolved and BC are Outpatient once fever has resolved and BC are

negative, if medically stablenegative, if medically stable An adverse outcome of these pts can occur An adverse outcome of these pts can occur

despite having received appropriate despite having received appropriate antimicrobial rx in a timely manner, despite antimicrobial rx in a timely manner, despite use of modern diagnostic techniques*use of modern diagnostic techniques*

• *Unpublished data from the Internat’l Collaboration on *Unpublished data from the Internat’l Collaboration on Endocarditis Prospective Cohort StudyEndocarditis Prospective Cohort Study

Surgery in Native Valve Surgery in Native Valve EndocarditisEndocarditis

1961 Key and colleagues excised fungal vegetations from 1961 Key and colleagues excised fungal vegetations from TV of patient w/ IETV of patient w/ IE

After 20 years of case by case treatment, retrospective After 20 years of case by case treatment, retrospective observational cohort study (n=513)* observational cohort study (n=513)*

pts with complicated left sided IE valve, surgery significantly pts with complicated left sided IE valve, surgery significantly reduced mortality at 6 mos*reduced mortality at 6 mos*

CHF is strongest indication for surgeryCHF is strongest indication for surgery 25% of pts with active endocarditis have surgery**25% of pts with active endocarditis have surgery** 1998 ACC/AHA guidelines1998 ACC/AHA guidelines

HF due to valve dysfnHF due to valve dysfn -perivalvular infection-perivalvular infection Persistent infectionPersistent infection -fungal endocarditis-fungal endocarditis Recurrent emboliRecurrent emboli -relapse-relapse

• **JJ Am Coll Cardiol 1998;32:3207Am Coll Cardiol 1998;32:3207

• ***Delahaye R, Long term prognosis of IE, Eur Heart J 1995;16:48-***Delahaye R, Long term prognosis of IE, Eur Heart J 1995;16:48-..

Follow up on my patientFollow up on my patient Blood cx: strep viridans Blood cx: strep viridans Rxd with nafcillin, vanco and gent; then gent 2 Rxd with nafcillin, vanco and gent; then gent 2

weeks and ceftriaxone 4-6weeksweeks and ceftriaxone 4-6weeks ID: severe valve disease, so broad coverage ID: severe valve disease, so broad coverage

until cx return; until cx return; Cardiology: 4/6 systolic plus diastolic murmur; Cardiology: 4/6 systolic plus diastolic murmur;

lisinopril for htn, cath prior to surgerylisinopril for htn, cath prior to surgery CT Surgery: TEE not needed, 6 wks iv antibx, CT Surgery: TEE not needed, 6 wks iv antibx,

repair vs. replacement of MVrepair vs. replacement of MV The patient: I want to work half time until The patient: I want to work half time until

surgery; I want to take care of my health. surgery; I want to take care of my health.

The physician as patientThe physician as patient

Subacute Bacterial Endocarditis observed: the Subacute Bacterial Endocarditis observed: the illness of Alfred S. Reinhart (1904-1931)illness of Alfred S. Reinhart (1904-1931)

The physician relies on what the pt conveys in a The physician relies on what the pt conveys in a language that itself must be interpretedlanguage that itself must be interpreted

One disease in which language plays a critical One disease in which language plays a critical role in awakening the clinician’s mind to it role in awakening the clinician’s mind to it presence is [SBE], for the seat of this disease is presence is [SBE], for the seat of this disease is a vital organ, whereas it’s manifestations are a vital organ, whereas it’s manifestations are almost entirely elsewherealmost entirely elsewhere

Harvard University medical studentHarvard University medical studentAlfred S. Reinhart, who died of SBEAlfred S. Reinhart, who died of SBE

Born in 1907, Boston, Son of immigrantsBorn in 1907, Boston, Son of immigrants Entered Harvard in 1924; HMS 1928, where he Entered Harvard in 1924; HMS 1928, where he

was a student until his death in 1931was a student until his death in 1931 ARF age 13 caused AIARF age 13 caused AI April-October, 1931 SBE gradually revealed April-October, 1931 SBE gradually revealed

itself to him and skeptical MDsitself to him and skeptical MDs Without antibx, his course of SBE was what the Without antibx, his course of SBE was what the

name implied: slow and inexorable worseningname implied: slow and inexorable worsening

Rheinhart’s illness*: “I took one glance at the Rheinhart’s illness*: “I took one glance at the pretty little collection of spots…and said, “I pretty little collection of spots…and said, “I

shall be dead in 6 months”.shall be dead in 6 months”. 1920 severe recurrent tonsillitis leads to T and A1920 severe recurrent tonsillitis leads to T and A 1921: PB Brigham with DOE and a murmur c/w AI1921: PB Brigham with DOE and a murmur c/w AI 1931: salvos of palpitations on exertion, petechial 1931: salvos of palpitations on exertion, petechial

showers on left armshowers on left arm House officer asked for his chief complaint: “ I have House officer asked for his chief complaint: “ I have

subacute bacterial endocarditis”subacute bacterial endocarditis” August : a splenic infarct led to BC: + Strep ViridansAugust : a splenic infarct led to BC: + Strep Viridans Sept: anemia, tender cutaneous nodules and joints, Sept: anemia, tender cutaneous nodules and joints,

excruciating pain from splenic infarctionexcruciating pain from splenic infarction October : attacks of transient aphasia , then R October : attacks of transient aphasia , then R

hemiplegiahemiplegia October 26: Rheinhart diesOctober 26: Rheinhart dies

Flegel, KM CMAJ 2002;167(12):1379Flegel, KM CMAJ 2002;167(12):1379

Final WordsFinal Words IE: consider as a diagnosisIE: consider as a diagnosis Importance of dialogue between MD and patient Importance of dialogue between MD and patient

[in determining IE][in determining IE] Rare opportunity in treating a fellow physicianRare opportunity in treating a fellow physician

““There is little evidence to indicate that Reinhart’s There is little evidence to indicate that Reinhart’s disease was any different than any one else’s, but his disease was any different than any one else’s, but his account allows the reader to know about it at a level account allows the reader to know about it at a level rarely encountered in clinical practice. One can only rarely encountered in clinical practice. One can only confront the suffering of another with humility, but we confront the suffering of another with humility, but we physicians are supposed to know something about physicians are supposed to know something about what a patient suffers…how routinely do we fail to what a patient suffers…how routinely do we fail to understand that for which we brazenly propose understand that for which we brazenly propose action” Kenneth Flegel action” Kenneth Flegel