Clinical Pathology Conference 62 year old woman with weakness and shortness of breath

1
Clinical Pathology Conference62 year old woman
with weakness and shortness of breath

• Heather Henderson, MD
• Internal Medicine Resident, PGY-3
• Scott White/Texas AM HSC

2
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

3
Case Presentation

• Past Medical History
• Relapsing, remitting multiple sclerosis
• HTN
• History of herpes zoster
• Raynauds phenomenon
• S/P TAH/BSO

4
Case Presentation

• Allergies NKDA
• Medications
• 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

5
Case Presentation

• Social History
• Tobacco None
• ETOH None
• Lives alone in Temple
• Inactive, but performs ADLs
• Family History
• Prostate Ca brother
• HTN - brother

6
Case Presentation

• Review of Systems
• 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 Raynauds

7
Physical Examination

• VS151/60, 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

8
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 LgtR to the
  level of the upper tibia
• Skin chronic venous stasis changes bilateral
  lower extremities
• Neuro bulk and tone normal in UEs, LEs with
  decrease motor strength with patient unable to
  lift left leg (known to be chronic) no new
  sensory deficits

9
Laboratory Evaluation

• BNP1940
• TnI0.07, CK35, CK-MB1.8
• Na140, K3.7, Cr1.0, BUN6
• TSH1.3
• WBC12.7, Hbg13.9, Plat391k
• Chol178, TG152, HDL67, LDL81

10
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

11
Chest X-ray

• Cardiomegaly
• Pulmonary vascular congestion
• Small bilateral pleural effusions

12
Echocardiogram

• LV enlargement with EF25 (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

13
Transesophageal Echocardiogram

• AI was mild to moderate
• Prominent myocardial trabeculations
• No LV thrombus

14
Coronary Angiogram

• Normal coronary anatomy
• No significant angiographic coronary artery
  disease

15
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

16
Things are not as they appear
17
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

18
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)

19
Classification of Primary Cardiomyopathies

• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
• Arrhythmogenic right ventricular cardiomyopathy
• Unclassified cardiomyopathy

20
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

21
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

22
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

23
Causes of Dilated Cardiomyopathy

• Ischemia
• Infectious diseases
• Coxsackievirus
• Cytomegalovirus
• HIV
• Varicella
• Hepatitis
• Epstein-Barr
• Echovirus
• Streptococci-rheumatic fever

• Typhoid fever
• Diphtheria
• Brucellosis
• Psittacosis
• Rickettsial disease
• Lyme disease
• Histoplasmosis
• Cryptococcosis
• Toxoplasmosis
• Trypanosomiasis
• Shistosomiasis
• Trichinosis

24
Causes of Dilated Cardiomyopathy

• Medications
• Chemotherapeutic agent
• Anthracyclines
• Cyclophosphamide
• Trastuzumab
• Antiretroviral drugs
• Zidovudine
• Didanosine
• Zalcitabine

• Phenothiazines
• Chloroquine
• Clozapine
• Toxins
• Ethanol
• Cocaine
• Amphetamines
• Cobalt
• Lead
• Mercury
• Carbon Monoxide
• Beryllium

25
Causes of Dilated Cardiomyopathy

• Rheumatologic diseases
• Systemic lupus
• Scleroderma
• Giant cell arteritis
• Endocrinologic disorders
• Hypo/Hyperthyroidism
• Growth hormone excess or deficiency
• Pheochromocytoma
• Diabetes Mellitus
• Cushings disease

• Neuromuscular diseases
• Duchennes Muscular Dystrophy
• Myotonic dystrophy
• Friedreichs ataxia
• Deposition Disease
• Hemochromatosis
• Amyloidosis

26
Causes of Dilated Cardiomyopathy

• Electrolyte abnormalities
• Hypocalcemia
• Hypophosphatemia
• Uremia
• Nutritional deficiencies
• Thiamine
• Selenium
• Carnitine

• Miscellaneous
• Peripartum cardiomyopathy
• Tachycardia
• Sarcoidosis
• Familial
• Sleep Apnea
• Autoimmune myocarditis
• Radiation
• Calcium Overload
• Oxygen free radical damage

27
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

28
Differential Diagnosis

• Dilated Cardiomyopathy
• Idiopathic dilated cardiomyopathy
• Valvular cardiomyopathy
• Medications
• Multiple Sclerosis
• Left ventricular noncompaction

29
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

30
Noninvasive Laboratory Evaluation

• Ca
• Phos
• Creatinine, BUN
• Thyroid function studies
• Iron studies
• HIV

31
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

32
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

33
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 (plt0.05)

34
Medications

• Amantadine
• lt1 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

35
More Medications

• Interferon beta 1a Avonex
• lt1 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

36
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

37
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

38
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

39
This is not a zebra!
40
Isolated Left Ventricular Noncompaction

• Characteristics of Isolated Left Ventricular
  Concompaction
• Prevalence
• Genetics
• Noncompaction associated with other diseases
• Clinical Manifestations
• Imaging
• Managment

41
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

42
Isolated Left Ventricular Noncompaction
43
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

44
Prevalence of Isolated Left Ventricular
Noncompaction

• A rare form of cardiomyopathy
• All adult echocardiograms with global LV
  dysfunction and an EF of lt45 were reviewed for
  signs of LV compaction
• 3.7 prevalence for LVEF lt45
• 0.26 for all patients
• A review from Switzerland identified 34 cases in
  15 years

45
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

46
Left Ventricular Noncompaction

• Congenital right or left ventricular outflow
  tract abnormalities
• Pulmonary atresia with intact ventricular septum
• Rarely seen with other congenital cardiac
  disorders
• Ebsteins anomaly
• Bicuspid aortic valve
• Aorta-to-left ventricular tunnel
• Congenitally corrected transposition
• Isomerism of the left atrial appendage
• VSD

47
Left Ventricular Noncompaction

• LVNC is associated with Neuromuscular diseases
• 86 patients with LVNC underwent neurological
  evaluation
• Metabolic myopathy(14), Lebers hereditary optic
  neuropathy(3), myotonic(2), Becker(1),
  Duchenne(1), NMD of unknown etiology in 32,
  normal in 13, 20 patients refused

48
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

49
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)

50
ECG in Noncompaction

• No characteristic changes
• Usually abnormal

51
Diagnosis of Noncompaction

• Echocardiography
• Cardiac MRI
• Cardiac CT Scan
• Left Ventriculography

52
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 gt21
  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

53
Echocardiogram
54
Echocardiogram
55
MRI in Noncompaction

• Noninvasive way to evaluate the presence and
  extent of myocardial fibrosis
• Cardiac MRI shows trabecular delayed
  hyperenhancement in left ventricle noncompaction

56
Cardiac MRI
57
Management

• No specific therapy
• Treat heart failure, arrhythmias, etc
• Holter monitoring once a year
• Heart transplantation

58
What is?
59
What is the answer?

• Final Diagnosis

60
What is the answer?

• Final Diagnosis
• Left Ventricular Noncompaction associated with
  Multiple Sclerosis
• vs.
• Idiopathic Dilated Cardiomyopathy

61
What is the answer?

• Final Diagnosis
• Left Ventricular Noncompaction associated with
  Multiple Sclerosis
• vs.
• Idiopathic Dilated Cardiomyopathy
• Diagnostic Study/Procedure
• Cardiac MRI

62
References

• Uptodate
• Kasper, Braunwald, Fauci, Hauser, Longo, Jameson.
  Harrisons Principles of Internal Medicine. 16th
  edition. 2005
• Zipes, Libby, Bonow, Braunwald. Braunwalds
  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 Sep15100(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
  Mar177(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
  Jan25(1)8-12.
• Zaragoza MV, et al. Noncompaction of the left
  ventricle primary cardiomyopathy with an elusive
  genetic etiology. Curr Opin Pediatr. 2007
  Dec19(6)619-27.

63
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
  Oct189(4)974-80.
• Briec F, et al. Recurrence of dilated
  cardiomyopathy after re-introduction of a
  tricyclic antidepressant. Arch Mal Coeur Vaiss.
  2006 Oct99(10)933-5.
• Ansari A, et al. Drug induced toxic myocarditis.
  Tex Heart Inst J. 200330(1)76-9.
• Akgul F, et al. Subclinical left ventricular
  dysfunction in multiple sclerosis. Acta Neurol
  Scand. 2006 Aug114(2)114-8.
• Cohen BA, Mikol DD. Mitoxantrone treatment of
  multiple sclerosis safety considerations.
  Neurology. 2004 Dec 2863(12 Suppl 6)s28-32.
• Zingler VC, et al. Assessment of potential
  cardiotoxic side effects of mitoxantrone in
  patients with multiple sclerosis. Eur Neurol.
  200554(1)28-33
• Stollberger C, Winkler-Dworak M, et al.
  Cardiology. 2007107(4)374-9.

64
Thank you

• Dr. Scott
• Dr. Pruett
• Dr. Hager
• Dr. Mock
• Dr. Brust

65
Questions?