Transcript Clinical Pathology Conference “62 year old woman with

Clinical Pathology
Conference
“62 year old woman with weakness
and shortness of breath”
Heather Henderson, MD
Internal Medicine Resident, PGY-3
Scott & White/Texas A&M HSC
Case Presentation
CC: “I am so weak and short of breath”
HPI: 62 year old white woman with
multiple sclerosis
2-3 days of worsening lower extremity
swelling
Increasing shortness of breath
Generalized weakness
No prior history of heart failure symptoms
Case Presentation
Past Medical History:
– Relapsing, remitting multiple sclerosis
– HTN
– History of herpes zoster
– Raynaud’s phenomenon
– S/P TAH/BSO
Case Presentation
Allergies: NKDA
Medications:
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Amantadine 200 mg po qam
Avonex 30 mcg IM qweekly
Baclofen 10 mg po qid
Amitriptyline 50 mg po qday
Oxybutynin 5 mg po bid
Maxzide 75/50 po daily, but has not taken for last
week
– Conjugated estrogen 0.625 mg po daily
Case Presentation
Social History:
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Tobacco: None
ETOH: None
Lives alone in Temple
Inactive, but performs ADL’s
Family History:
– Prostate Ca – brother
– HTN - brother
Case Presentation
Review of Systems:
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Weak with poor appetite
Dyspnea on exertion with some wheezing lately
No fever or chills
Constipated for last 2-3 days
Nauseated at times without emesis
No headaches or blurred vision
No dysuria
No recent problem with Raynaud’s
Physical Examination
VS:151/60, 120, 20, 93% RA, 36.1, Wt: 91kg
Gen: wn/wd white woman appearing chronically ill, weak,
and tired, but no acute distress
HEENT: normal except JVP =10 cm of water
Chest: bilateral breath sounds decreased bilateral lower
lobes, bibasilar crackles
CV: PMI slightly displaced inferolaterally; tachycardic at
120 bpm; normal S1 and S2 with normal splitting, no S3
or S4 gallop; II/VI diastolic decrescendo murmur at LLSB
with patient sitting up; pulses 2+/2+, bilateral throughout
Physical Examination
Back: pitting sacral edema
Abd: soft, nd/nt; nabs, no abd bruit, no
hepatosplenomegaly
Ext: no clubbing/cyanosis; positive 0.5cm depth pitting
edema of the lower extremities L>R to the level of the
upper tibia
Skin: chronic venous stasis changes bilateral lower
extremities
Neuro: bulk and tone normal in UE’s, LE’s with
decrease motor strength with patient unable to lift left leg
(known to be chronic); no new sensory deficits
Laboratory Evaluation
BNP=1940
TnI=0.07, CK=35, CK-MB=1.8
Na=140, K=3.7, Cr=1.0, BUN=6
TSH=1.3
WBC=12.7, Hbg=13.9, Plat=391k
Chol=178, TG=152, HDL=67, LDL=81
Electrocardiogram
NSR, rate = 84
Marked t-wave inversion in the anterior
leads and scooping of the ST segment in
the inferior leads, suggests ischemia
No voltage criteria for LVH
Chest X-ray
Cardiomegaly
Pulmonary vascular congestion
Small bilateral pleural effusions
Echocardiogram
LV enlargement with EF=25%
(globally depressed)
Normal LV wall thickness
Increased echo densities in the LV apex
suggesting possible thrombus
LA enlargement with mild MR
Moderate to severe AI with normal aortic
root size
Transesophageal
Echocardiogram
AI was mild to moderate
Prominent myocardial trabeculations
No LV thrombus
Coronary Angiogram
Normal coronary anatomy
No significant angiographic coronary
artery disease
Problem List
Weakness
Shortness of breath
Multiple Sclerosis
Congestive Heart
Failure
Dilated
Cardiomyopathy
EF =25%
Tachycardia
Aortic Insufficiency
with normal aortic root
Prominent myocardial
trabeculations
No significant
Coronary Artery
Disease
Things are not as they appear
Objectives
Define cardiomyopathy
Discussion of causes of dilated cardiomyopathy
Diagnostic evaluation of a dilated
cardiomyopathy
Review of the literature for a correlation between
multiple sclerosis and cardiomyopathy
A discussion of a rare cause of dilated
cardiomyopathy
Cardiomyopathy Defined
A group of disorders in which the dominant
feature is direct involvement of the heart
muscle.
(Not the result of pericardial, hypertensive,
congenital, or valvular diseases)
Classification of Primary
Cardiomyopathies
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Arrhythmogenic right ventricular
cardiomyopathy
Unclassified cardiomyopathy
Specific Cardiomyopathies
Ischemic cardiomyopathy
Valvular cardiomyopathy
Hypertensive cardiomyopathy
Inflammatory cardiomyopathy
Metabolic cardiomyopathy
General-systemic disease cardiomyopathy
Muscular dystrophies
Neuromuscular disorders
Sensitivity and toxic reactions
Peripartal cardiomyopathy
Dilated Cardiomyopathy
5-8 cases per 100,000 population/year
10,000 deaths each year in the US
46,000 hospitalizations each year in the
United States
¼ of the cases of congestive heart failure
in the United States
75 different diseases cause DCM
Objectives
Define cardiomyopathy
Discussion of causes of dilated cardiomyopathy
Diagnostic evaluation of a dilated
cardiomyopathy
Review of the literature for a correlation between
multiple sclerosis and cardiomyopathy
A discussion of a rare cause of dilated
cardiomyopathy
Causes of Dilated
Cardiomyopathy
Ischemia
Infectious diseases
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Coxsackievirus
Cytomegalovirus
HIV
Varicella
Hepatitis
Epstein-Barr
Echovirus
Streptococci-rheumatic
fever
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Typhoid fever
Diphtheria
Brucellosis
Psittacosis
Rickettsial disease
Lyme disease
Histoplasmosis
Cryptococcosis
Toxoplasmosis
Trypanosomiasis
Shistosomiasis
Trichinosis
Causes of Dilated
Cardiomyopathy
Medications
– Chemotherapeutic agent
Anthracyclines
Cyclophosphamide
Trastuzumab
– Antiretroviral drugs
Zidovudine
Didanosine
Zalcitabine
– Phenothiazines
– Chloroquine
– Clozapine
Toxins
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Ethanol
Cocaine
Amphetamines
Cobalt
Lead
Mercury
Carbon Monoxide
Beryllium
Causes of Dilated
Cardiomyopathy
Rheumatologic diseases
– Systemic lupus
– Scleroderma
– Giant cell arteritis
Endocrinologic disorders
– Hypo/Hyperthyroidism
– Growth hormone excess or
deficiency
– Pheochromocytoma
– Diabetes Mellitus
– Cushing’s disease
Neuromuscular diseases
– Duchenne’s Muscular
Dystrophy
– Myotonic dystrophy
– Friedreich’s ataxia
Deposition Disease
– Hemochromatosis
– Amyloidosis
Causes of Dilated
Cardiomyopathy
Electrolyte abnormalities
– Hypocalcemia
– Hypophosphatemia
– Uremia
Nutritional deficiencies
– Thiamine
– Selenium
– Carnitine
Miscellaneous
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Peripartum cardiomyopathy
Tachycardia
Sarcoidosis
Familial
Sleep Apnea
Autoimmune myocarditis
Radiation
Calcium Overload
Oxygen free radical
damage
Frequency of Different Causes
Idiopathic – 50 percent
Myocarditis – 9 percent
Ischemic heart disease – 7 percent
Infiltrative disease – 5 percent
Peripartum cardiomyopathy – 4 percent
HIV infection – 4 percent
Connective tissue disease – 3 percent
Substance abuse – 3 percent
Doxorubicin – 1 percent
Other – 10 percent
Differential Diagnosis
Dilated Cardiomyopathy
– Idiopathic dilated cardiomyopathy
– Valvular cardiomyopathy
– Medications
– Multiple Sclerosis
– Left ventricular noncompaction
Objectives
Define cardiomyopathy
Discussion of causes of dilated cardiomyopathy
Diagnostic evaluation of a dilated
cardiomyopathy
Review of the literature for a correlation between
multiple sclerosis and cardiomyopathy
A discussion of a rare cause of dilated
cardiomyopathy
Noninvasive Laboratory Evaluation
Ca
Phos
Creatinine, BUN
Thyroid function studies
Iron studies
HIV
Invasive Evaluation
Endomyocardial biopsy
– May be of benefit in certain situations
– Definite clinical benefit
Infiltrative disorders
Anthracycline toxicity
Cardiac transplant rejection
– No definitive pattern histologically in DCM
– Estimated that a specific diagnosis is obtained by
biopsy in fewer than 10 percent of patients
Cardiac Catheterization and Angiography
– To determine ischemic disease
Objectives
Define cardiomyopathy
Discussion of causes of dilated cardiomyopathy
Diagnostic evaluation of a dilated
cardiomyopathy
Review of the literature for a correlation between
multiple sclerosis and cardiomyopathy
A discussion of a rare cause of dilated
cardiomyopathy
Multiple Sclerosis and
Cardiomyopathy: Is there a link?
Subclinical left ventricular dysfunction in
multiple sclerosis, per Akgul
41 patients with MS and 32 healthy
controls
LV ejection fraction was decreased in MS
patients compared with controls (p<0.05)
Medications
Amantadine
<1% CHF
1%-10% orthostatic hypotension,
peripheral edema
Use in caution in patients with heart
failure, peripheral edema, or orthostatic
hypotension
Triamterene has been reported to increase
the potential for toxicity with amantadine
More Medications
Interferon beta 1a – Avonex
<1% cardiomyopathy, CHF
1%-10% chest pain, vasodilatation
Use in caution in patients with pre-existing
cardiovascular disease
Interferons increase the adverse effects of
ACE inhibitors, specifically the
development of granulocytopenia
More Medications
Amitriptyline
– Rare cause of cardiomyopathy
– 2 case reports in the literature:
Case report: Cardiomyopathy developed during
treatment with imipramine, recovered after
withdrawal, recurred 9 years later during treatment
with amitriptyline
Case report: Cardiomyopathy in a patient on
amitriptyline and perphenazine
More Medications
Mitoxantrone
Cause of cardiomyopathy
Dose related, approved cumulative dose is
140 mg/m2
Prospective study in Germany in 73
patients showed no significant change in
end-diastolic diameter, end-systolic
diameter, fractional shortening, or EF in
23 month follow up with mean dose of 114
mg/m2
Objectives
Define cardiomyopathy
Discussion of causes of dilated cardiomyopathy
Diagnostic evaluation of a dilated
cardiomyopathy
Review of the literature for a correlation between
multiple sclerosis and cardiomyopathy
A discussion of a rare cause of dilated
cardiomyopathy
This is not a zebra!
Isolated Left Ventricular
Noncompaction
Characteristics of Isolated Left Ventricular
Concompaction
Prevalence
Genetics
Noncompaction associated with other diseases
Clinical Manifestations
Imaging
Managment
Isolated Left Ventricular
Noncompaction
Characterized by the following feautures:
– Altered myocardial wall
– Prominent trabeculae and deep
intertrabecular recesses
– Thickened myocardium with two layers
consisting of compacted and noncompacted
myocardium
Isolated Left Ventricular
Noncompaction
Isolated Left Ventricular
Noncompaction
Also Characterized by the following
feautures:
– Continuity between the left ventricular cavity
and the deep intratrabecular recesses, which
are filled with blood
– No communication to epicardial coronaries
– Decreased coronary flow reserve
Prevalence of Isolated Left
Ventricular Noncompaction
A rare form of cardiomyopathy
All adult echocardiograms with global LV
dysfunction and an EF of <45% were
reviewed for signs of LV compaction
3.7% prevalence for LVEF <45%
0.26% for all patients
A review from Switzerland identified 34
cases in 15 years
Genetics of Isolated Left Ventricular
Noncompaction
LVNC can be familial
Mutations have been found in the following
genes
– G4.5
– P121L
– Cypher/ZASP
– Chromosome 11p15
Family Screening
Left Ventricular Noncompaction
Congenital right or left ventricular outflow tract
abnormalities
– Pulmonary atresia with intact ventricular septum
Rarely seen with other congenital cardiac
disorders
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Ebstein’s anomaly
Bicuspid aortic valve
Aorta-to-left ventricular tunnel
Congenitally corrected transposition
Isomerism of the left atrial appendage
VSD
Left Ventricular Noncompaction
LVNC is associated with Neuromuscular
diseases
86 patients with LVNC underwent
neurological evaluation
– Metabolic myopathy(14), Leber’s hereditary
optic neuropathy(3), myotonic(2), Becker(1),
Duchenne(1), NMD of unknown etiology in 32,
normal in 13, 20 patients refused
LV Noncompaction and NMD
Noncompaction and neuromuscular
disease in a nonagerian
– 94 year old male presented with a surprising
find of left ventricle hypertrabeculation
– Upon neurologic investigation, patient had a
polyneuropathy and possible myopathy
Clinical Manifestations
Report from Switzerland on 34 patients
– At the time of diagnosis, clinical
manifestations included:
Dyspnea – 27 (79%)
NYHA Class III or IV heart failure – 12 (35%)
Chest Pain – 9 (26%)
Chronic Atrial Fibrillation – 9 (26%)
ECG in Noncompaction
No characteristic changes
Usually abnormal
Diagnosis of Noncompaction
Echocardiography
Cardiac MRI
Cardiac CT Scan
Left Ventriculography
Echocardiographic Criteria for
Diagnosis
Absence of coexisting cardiac abnormalities
Segmental thickening of the left ventricular myocardial
wall consisting of two layers; a ratio of noncompacted to
compacted myocardium of >2:1 and end-systole with
thickening of the myocardial wall
Predominant localization of the pathology in the apical
mid-lateral, and mid-inferior regions of the left ventricle
Color doppler evidence of flow within the deep perfused
intertrabecular recesses
Echocardiogram
Echocardiogram
MRI in Noncompaction
Noninvasive way to evaluate the presence
and extent of myocardial fibrosis
Cardiac MRI shows trabecular delayed
hyperenhancement in left ventricle
noncompaction
Cardiac MRI
Management
No specific therapy
– Treat heart failure, arrhythmias, etc
Holter monitoring once a year
Heart transplantation
What is?
What is the answer?
Final Diagnosis
What is the answer?
Final Diagnosis
Left Ventricular Noncompaction
associated with Multiple Sclerosis
vs.
Idiopathic Dilated Cardiomyopathy
What is the answer?
Final Diagnosis
Left Ventricular Noncompaction associated
with Multiple Sclerosis
vs.
Idiopathic Dilated Cardiomyopathy
Diagnostic Study/Procedure
Cardiac MRI
References
Uptodate
Kasper, Braunwald, Fauci, Hauser, Longo, Jameson. Harrison’s Principles
of Internal Medicine. 16th edition. 2005
Zipes, Libby, Bonow, Braunwald. Braunwald’s Heart Disease Textbook of
Cardiovascular Medicine. 7th edition. 2005
Kuhn H, Lawrenz T, Beer G. Indication for Myocardial Biopsy in myocarditis
and dilated cardiomyopathy. Med Klin. 2005 Sep15;100(9):553-61.
Alsaileek AA, Syed I, Seward JB, Julsrud P. Myocardial fibrosis of left
ventricle: Magnetic resonance imaging in noncompaction. J Magn Reson
Imaging. 2008 Jan 24
Bruder O, et al. Detection and characterization of left ventricular thrombi by
MRI compared to transthoracic echocardiography. Rofo. 2005
Mar;177(3):344-9.
Sandhu R, et al. Prevalence and characteristics of left ventricular
noncompaction in a community hospital cohort of patients with systolic
dysfunction. Echocardiography. 2008 Jan;25(1):8-12.
Zaragoza MV, et al. Noncompaction of the left ventricle: primary
cardiomyopathy with an elusive genetic etiology. Curr Opin Pediatr. 2007
Dec;19(6):619-27.
References
Finsterer J, et al. Noncompaction and neuromuscular disease with positive
troponin-T in a nonagenerian. Clin Cardiol. 2007 Oct;(10):527-8.
Dodd JD, et al. Quantification of left ventricular noncompaction and
trabecular delayed hyperenhancement with cardiac MRI: correlation with
clinical severity. AJR AM J Roentgenol. 2007 Oct;189(4):974-80.
Briec F, et al. Recurrence of dilated cardiomyopathy after re-introduction of
a tricyclic antidepressant. Arch Mal Coeur Vaiss. 2006 Oct;99(10):933-5.
Ansari A, et al. Drug induced toxic myocarditis. Tex Heart Inst J.
2003;30(1):76-9.
Akgul F, et al. Subclinical left ventricular dysfunction in multiple sclerosis.
Acta Neurol Scand. 2006 Aug;114(2):114-8.
Cohen BA, Mikol DD. Mitoxantrone treatment of multiple sclerosis: safety
considerations. Neurology. 2004 Dec 28;63(12 Suppl 6):s28-32.
Zingler VC, et al. Assessment of potential cardiotoxic side effects of
mitoxantrone in patients with multiple sclerosis. Eur Neurol. 2005;54(1):2833
Stollberger C, Winkler-Dworak M, et al. Cardiology. 2007;107(4):374-9.
Thank you
Dr. Scott
Dr. Pruett
Dr. Hager
Dr. Mock
Dr. Brust
Questions?