53 year old man

Question 1

Monomorphic ventricular tachycardia vs polymorphic ventricular tachycardia

Answer 1

• Mono- single focus and single port of exit
• Poly- multiple focus and multiple exits

Question 2

Causes of polymorphic VT

Answer 2

• Acute MI
• Abnormalities of ion channels
• Idiopathic ventricular fibrillation
• Structural disease: hypertrophy, recent infarction, cardiomyopathy

Question 3

Causes of monomorphic VT

Answer 3

Scar-related reentry and Purkinje disease

Question 4

What do GP 2b/3a antagonists do?

Answer 4

They block the final common pathway of platelet aggregation
After platelets are activated by local agonists, fibrinogen binds to the platelet surface glycoprotein 2b/3a receptor to link adjacent platelets and cause platelet aggregation. Intraluminal thrombus propagation follows platelet aggregation

Question 5

What can antiarrhythmic drugs be divided into?

Answer 5

Four classes:
Class 1: Na+ channel blocker (e.g. lidocaine and quinidine)
Class 2: Beta blockers (e.g. propanolol and metoprolol
Class 3: K+ channel blocker (e..g. amiodarone)
Class 4: Ca2+ channel blocker (e.g. verapamil)

Question 6

What is a right bundle branch block?

Answer 6

Electrical activity through the His-Purkinje system (responsible for the rapid electric conduction in the ventricles. It relays electrical impulses from the atrioventricular node to the muscle cells and, thus, coordinates the contraction of ventricles in order to ensure proper cardiac pump function.) is interrupted, especially through the right bundle

Question 7

What can right bundle branch block be caused by?

Answer 7

• Structural heart disease
• Iatrogenic
• Athletes (incomplete)

Question 8

What can disorders of myocarditis be divided into?

Answer 8

• Disorders that cause inflammatory myocarditis can be narrowed down to
  infectious and autoimmune diseases.
• Approximately 50% (82% in children) of the time, miocarditis is classified as idiopathic

Question 9

Why is infectious myocarditis, in particular parasitic not likely in this patient?

Answer 9

• Echinococcus and T. solium may explain his recent diarrheal illness. However , myocarditis is due to a ruptured cyst that causes direct inflammation, and imaging studies in this patient did not show evidence of a cystic lesion.
• Strongyloides and ascaris also cause gastrointestinal symptoms. However,
  myocarditis is due to a high parasitic burden resulting in a systemic eosinophilic
  response that can then cause inflammation in distant organs. T he absence of a
  clinically significant peripheral eosinophilia and the history of gastrointestinal
  symptoms that spontaneously resolved make them an unlikely cause.
• Giardia has been identified in some patients with acute myocarditis, although
  its precise role in the pathogenesis has not been elucidated . Patients with
  giardiasis may have indolent or relapsing gastrointestinal syndromes. Although
  giardiasis has not been definitively ruled out in this patient, the absence of
  ongoing gastrointestinal symptoms make this an unlikely diagnosis.

Question 10

Why is autoimmune myocarditis not a possibility in this patient?

Answer 10

• Hyper-eosinophilic syndrome (in the absence of a parasitic infection)
  should be considered. Typically the degree of organ involvement
  parallels the severity of peripheral eosinophilia , but since Roy did not
  have a significant eosinophilia, this diagnosis is unlikely
• Celiac disease has an increased prevalence in patients with acute
  myocarditis. Although the exact mechanism is not well understood,
  celiac disease is presumed to cause myocarditis by means of bacterial
  translocation and immune dysregulation . Celiac disease can cause
  indolent or relapsing gastrointestinal symptoms. Although this diagnosis
  cannot be ruled out, it is unlikely to cause myocarditis in the absence of
  ongoing gastrointestinal symptoms or other systemic manifestations.

Question 11

Which etiologies of myocarditis also show electrical instability?

Answer 11

Two distinct types of myocarditis show significant electrical instability:
1. giant cell myocarditis
2. cardiac sarcoidosis

Question 12

Signs on patients of giant cell myocarditis and cardiac sarcoidosis on heart

Answer 12

Sarcoidosis: Rapid onset HF and ventricular tachyarrhythmia accompanied by conduction block
Giant cell myocarditis: Typically with rapidly progressive HF and ventricular tachycardia

Question 13

What is giant cell myocarditis and cardiac sarcoidosis characterized by?

Answer 13

• Giant cell myocarditis is characterized by a mixed inflammatory infiltrate
  that affects the heart alone, and it has been linked to infectious and
  systemic autoimmune diseases. The characteristic pathological features
  include multinucleated giant cells and myocyte necrosis.
• Sarcoidosis is known to cause systemic manifestations , but it sometimes
  affects the heart alone, as the sole manifestation. The pathological
  features include multinucleated giant cells, but the hallmark features of
  non caseating granulomas, fibrosis, and scarring are more prominent.

Question 14

Treatment of giant cell myocarditis vs cardiac sarcoidosis

Answer 14

Parsing out these diseases is quite important, since giant cell
myocarditis require aggressive treatment with multiple
immunosuppressive medications, whereas cardiac sarcoidosis can be
treated with glucocorticoids alone.

Question 15

Diagnosis of cardiac sarcoidosis and giant cell myocarditis historicaly

Answer 15

• These two entities are clinically indistinguishable.
• For many years, giant cell myocarditis and cardiac sarcoidosis were
  considered to be the same disease, characterized by the presence of
  multinucleated giant cells with or without granulomas.
• They are now recognized as two pathologically distinct entities , but
  distinguishing them clinically remains a challenge.

Question 16

Differential diagnosis of giant cell myocarditis vs cardiac sarcoidosis

Answer 16

• Several features of this patient’s presentation point toward a diagnosis of
  giant cell myocarditis rather than cardiac sarcoidosis , including his white
  race and the rapidly progressive and fulminant course of the disease.
• Giant cell myocarditis causes myocyte necrosis, which is the most likely
  explanation for the aggressive nature; in contrast, sarcoidosis typically
  causes fibrosis and is associated with a more indolent progression.
• MRI findings may be helpful in distinguishing the two diseases.
  Involvement of the right ventricular side of basal interventricular septum is
  specific for sarcoidosis but was absent, whereas subendocardial cardiac
  involvement is specific for giant cell myocarditis.

Question 17

Definition and Microscopic pathology of giant cell myocarditis

Answer 17

• Widespread or serpiginous inflammation with myocyte necrosis in the absence of well formed granulomas of specific etiology
• Widespread or serpiginous inflammation with giant cells, lymphocytes and often eosinophils. Myocyte necrosis is always present. Poorly formed granulomas may be seen

Question 18

Definition and Microscopic pathology of cardiac sarcoidosis

Answer 18

• Granulomatous myocarditis with no evidence of infectious or other specific cause
• Non necrotizing/caseating granulomas, fibrosis with few eosinophils. Myocyte necrosis is rare

Question 19

T cells and eosinophils in myocarditis

Answer 19

• Sarcoidosis is typically associated with the presence of compact
  granulomas, extensive scarring, and more CD4 expressing helper T cells
  than CD8 expressing cytotoxic T cells.
• In acute necrotizing eosinophilic myocarditis, eosinophils are numerous
  and giant cells may be present but tend not to be located at the leading
  edge of the inflammation, as are typically seen in giant cell myocarditis.

Question 20

Treatment approach for giant cell myocarditis

Answer 20

• Immunosuppression with glucocorticoids alone does not increase
  survival or decrease the likelihood of heart transplantation , although
  combined treatment with glucocorticoids and agents as azathioprine ,
  calcineurin inhibitors , antithymocyte globulin , mycophenolate mofetil , or
  methotrexate may increase long term survival
• Ventricular tachycardia commonly occurs in patients who do not undergo
  heart transplantation , and thus , it is appropriate ICD implantation even
  when left ventricular dysfunction is only mild to moderate
• Mechanical circulatory support is often necessary during early treatment
  and in patients for whom heart transplantation is indicated
  Many patients have biventricular dysfunction , and extracorporeal
  membrane oxygenation can provide lifesaving stability
  *
  Short term treatment with extracorporeal membrane oxygenation may
  be transitioned to more permanent treatment with a ventricular assist
  device implanted on the left or right side of the heart (or both ), either as
  destination therapy or as a bridge to heart transplantation
• For patients who do not have a response to immunosuppressive therapy and receive mechanical circulatory support , heart transplantation is the
  best long term therapeutic option.

Question 21

Recurrence of cardiac sarcoidosis and giant cell myocarditis in heart transplant patients

Answer 21

• Sufficient data about the recurrence of cardiac sarcoidosis in the transplanted heart, which has been well described. The good news about it is that, with or augmentation of immunosuppression it usually resolves
• We have less information about the recurrence of giant cell myocarditis, because not many patients have undergone transplantation. In general, recurrence rate is very low. Similar to sarcoidosis, recurrent giant-cell myocarditis is usually effectively treated with enhance immunosuppression

Question 22

Cause of giant cell myocarditis

Answer 22

• The cause is generally unknown, and the disease is limited to the heart.
• Autoimmune disorders (e.g., IBD, fibromyalgia , Hashimoto’s thyroiditis )
  may occur in up to 20% of patients
• In addition, giant cell myocarditis may be part of a systemic giant cell
  polymyositis , which occurs as a paraneoplastic syndrome in thymoma
• On rare occasions, drug reactions can result in a pattern of inflammatory
  response similar to that of giant cell myocarditis.

Question 23

Prognosis of giant cell myocarditis

Answer 23

• Giant cell myocarditis is aggressive and often fatal , with a rate of death
  or heart transplantation of 89% and a median survival of only 6 months
  after symptom onset
• The disease can progress rapidly , leading to cardiogenic shock or intractable ventricular arrhythmias as in this patient
  \

Question 24

When do patients usually present and what are the clinical features of giant cell myocarditis

Answer 24

• Patients typically present in the fourth or fifth decade
• The clinical presentation can include:
  heart failure or new onset cardiomyopathy in 75% of patients
  syncope
  sudden death due to ventricular tachycardia in 15%
  heart block (in 5%)
• An initial electrocardiogram frequently shows evidence of bifascicular
  block (as in this patient) or left bundle branch block.

Question 25

Cardiac MRI usefulness in giant cell myocarditis diagnosis

Answer 25

Cardiac MRI is useful in detecting acute inflammation in all forms of
acute myocarditis but cannot be used to differentiate between fulminant
lymphocytic myocarditis and giant cell disease

Question 26

What is essential in the diagnosis of giant cell myocarditis

Answer 26

Endomyocardial biopsy is essential and should be performed promptly

Question 27

Positive inotropic agents in giant cell myocarditis

Answer 27

Positive inotropic agents often exacerbate underlying ventricular
arrhythmias and are generally avoided

Question 28

Risk of acute transplant rejection in giant cell myocarditis

Answer 28

The risk of acute rejection is higher with giant cell myocarditis than with dilated cardiomyopathy 16% vs. 5%), but no substantial difference in survival has been reported

Question 29

What is myocarditis?

Answer 29

Inflammatory disease of the myocardium occuring in the absence of ischemia

Question 30

How is myocarditis diagnosed

Answer 30

Diagnosed by established histological/immunological, and immunohistochemical criteria

Question 31

Inflammatory cardiomyopathy definition

Answer 31

Myocarditis in association with cardiac dysfunction

Question 32

Dallas criteria

Answer 32

Question 33

WHO Marburg classification for acute myocarditis

Answer 33

Necrosis or degeneration is compulsory

Question 34

Acute myocarditis epidemiology

Answer 34

• Age is around 20-51 years
• Slight preponderance in men

Question 35

Laboratory studies to be performed in patients with myocarditis

Answer 35

• CBC to check for leukocytosis (may demonstrate eosinophilia)
• Elevated ESR or other APR such as CRP
• Rheumatological screening to rule out systemic inflammatory diseases
• Enzymes for cardiac myonecrosis (I or T and CKMB)

Question 36

Troponin and CKM elevation in myocarditis

Answer 36

• Cardiac troponin I or T is elevated in at least 50% of patients with biopsy proven myocarditis
• CKMB is are elevated in only 5.7% of patients with biopsy proven myocarditis

Question 37

Sensitivity and features of ECG for myocarditis

Answer 37

Sinus tachycardia with non specific ST segment and T wave abnormalities
Sensitivity Low at around 47%
Presence of Q waves or LBBB block is associated with higher rates of death or cardiac transplantation

Question 38

Tissue characteristics of myocarditis on Cardiac MRI

Answer 38

• Edema
• Hyperemia and capillary leak (if done with myocardial early gadolinium enhancement)
• Necrosis and fibrosis (late gadolinium enhancement)

Question 39

Myocarditis treatment

Answer 39

Question 40

Viruses in myocarditis

Answer 40