B P6 C55 Myocarditis Flashcards
_____ refers to inflammation of the heart muscle occurring as a result of exposure to either discrete external antigens, such as viruses, bacteria, parasites, toxins, or drugs, or internal triggers, such as autoimmune activation against self-antigens.
Classic myocarditis
Although _____ remains the most commonly identified cause of myocarditis, drug hypersensitivity and toxic drug reactions, other infections, and peripartum cardiomyopathy also can lead to myocarditis.
Viral infection
The pathogenesis of myocarditis is a classic paradigm of cardiac injury followed by _____ response from the host resulting in cardiac inflammation.
Immunologic
Indeed, more than 20 viruses have been associated with myocarditis, and the most frequent are currently _____.
Parvovirus B19 (B19V)
HHV-6
If the host immune response is overwhelming or inappropriate, the inflammation may destroy the heart tissue acutely or may linger, producing cardiac remodeling that leads to _____.
DCM
HF
Death
Disability from myocarditis is largely due to _____.
Heart Failure
The death rate from myocarditis is higher in the _____ year of life than between ages 1 and 14 years for both males and females.
After age 15 years, DALYs, number of deaths, and death rate due to myocarditis are higher in males than females.
1st year of life
After age 15: M>F
Myocarditis is responsible for sudden cardiovascular death in approximately ___% of infants, ___% of children, and ___% of young athletes
2% - Infants
5% - Children
5-14% Young athletes
The standard Dallas criteria define idiopathic myocarditis as an _____.
Inflammatory infiltrate of the myocardium
+
Necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease
The presence of viral genomes in heart tissue may indicate an active infectious myocarditis.
In the posttransplantation setting, the presence of viral genomes in myocardial biopsy material predicts future _____ in children
Rejection episodes and graft loss
In most cases, myocarditis is triggered by an inciting event, such as _____ that activates the immune response
Infection
or
Exposure to a drug or toxin
_____ has been implicated as one of the most common infectious causes of myocarditis
Viral infection
Modern virologic and molecular techniques have demonstrated that _____ are among the most commonly identified infectious agents in myocarditis.
Adenoviruses
Parvovirus
Enteroviruses
Endomyocardial Biopsy Diagnosis of Myocarditis: The Dallas Criteria Definition
Idiopathic myocarditis: “an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease”
Endomyocardial Biopsy Diagnosis of Myocarditis: The Dallas Criteria Classification
*First biopsy
Myocarditis with or without fibrosis
Borderline myocarditis (repeat biopsy may be indicated)
No myocarditis
*Subsequent biopsy
Ongoing (persistent) myocarditis +/- fibrosis
Resolving (healing) myocarditis +/- fibrosis
Resolved (healed) myocarditis +/- fibrosis
Possible subclinical acute myocarditis criteria
In the clinical context of possible myocardial injury WITHOUT cardiovascular symptoms but with at least one of the following:
Biomarkers of cardiac injury raised
ECG findings suggestive of cardiac injury
Abnormal cardiac function on echocardiogram or CMR
Probable acute myocarditis criteria
In clinical context of possible myocardial injury WITH cardiovascular symptoms and at least one of the following:
Biomarkers of cardiac injury raised
ECG findings suggestive of cardiac injury
Abnormal cardiac function on echocardiogram or CMR
Definite myocarditis criteria
Histologic or immunohistologic evidence of myocarditis
_____ virus infection appears to be mainly associated with cardiomyopathy in Asian countries such as Japan
Hepatitis C
Frequent causes of myocarditis
Adenovirus
Coxsackievirus
Cytomegalovirus
Anthracyclines
Cocaine
Alcohol
As the world has turned its attention to the COVID-19 pandemic, it became clear during the early stages of the disease that patients who were admitted to the hospital for COVID-19 had a ____% incidence of myocardial injury manifested by an increase in troponin and type B natriuretic factor
20-35%
The pathogenesis of cardiac injury in COVID-19 is complex with mechanisms that include _____.
Viral mediated injury
Microvascular dysfunction/ thrombosis
Cytokines
Type II myocardial infarctions
It was assumed initially that this myocardial injury was secondary to a _____ form of myocarditis precipitated by infection of cardiac cells by SARS-CoV-2.
Classical form
The histological features seen at autopsy include _____.
Classic lymphocytic myocarditis is relatively uncommon in COVID-19 patients.
Increased macrophages and cytokine elevation
In retrospective series and autopsy studies in patients infected with HIV, the incidence of cardiac involvement ranged from _____%.
25-75%
Myocarditis with _____ infiltration has been reported in 40% to 52% of patients who die of acquired immunodeficiency syndrome (AIDS)
Lymphocytic infilatration
The incidence of cardiomyopathy, myocarditis, and pericardial diseases correlates with the severity of the HIV infection as measured by a low _____ or high _____.
Low CD4+ count or high viral titers.
In the post–antiretroviral therapy era, _____ are the major cardiovascular diseases that occur in HIV-infected patients in the United States.
ACS and CAD
Nonviral pathogens such as bacteria and parasites can affect the heart and, in some cases, activate an immune reaction in the heart.
Virtually any bacterial agent can cause ______, but it does not necessarily mean that the bacterium has infected the myocardium.
Myocardial dysfunction
In the case of sepsis or other severe bacterial infections, the myocardial dysfunction generally is attributed to ______.
Activation of inflammatory mediators
Of note, however, bloodstream infection by virtually any bacterial infection can result in metastatic foci in the myocardium.
This finding is most commonly associated with _____.
Bacterial endocarditis
Some bacterial infections are well known to have specific effects on the heart that can be mediated by direct infection or activation of inflammatory mechanisms.
The most common of these include _____.
Diphtheria
RHD
Streptococcal infections
Myocardial involvement with _____ is a serious complication and is the most common cause of death in diphtheria.
Corynebacterium diphtheriae
C. diphtheriae produces an _____ that severely damages the myocardium and the cardiac conduction system.
Exotoxin
Cardiac damage is due to the liberation of this exotoxin, which inhibits protein synthesis by interfering with host translational mechanisms.
The toxin appears to have an affinity for the cardiac conduction system. Both antitoxin therapy and antibiotics are important in the treatment of diphtheria.
The most commonly detected cardiac com-plication after _____ infection is acute rheumatic fever, which is followed by rheumatic valve disease in approximately 60% of affected patients.
Beta-hemolytic streptococcal
Rarely, involvement of the heart by the streptococcus may produce a ______ distinct from acute rheumatic carditis.
Nonrheumatic myocarditis
This clinical entity is characterized by the presence of an interstitial infiltrate composed of mononuclear cells with occasional polymorphonuclear leukocytes, which may be focal or diffuse
In contrast with rheumatic heart disease, streptococcal myocarditis usually occurs _____.
Coincident with the acute infection or within a few days of the pharyngitis
Tuberculous involvement of the myocardium occurs by means of ______.
(1) Hematogenous
(2) Lymphatic spread
(3) Arise directly from contiguous structures and may cause nodular, miliary, or diffuse infiltrative disease
In Whipple Disease, electron microscopy has demonstrated rod-shaped structures in the myocardium similar to those found in the small intestine, representing the causative agent of the disease, Tropheryma whipplei, a gram-negative bacillus related to the actinomycetes. An inflammatory infiltrate and foci of fibrosis also may be present. The valvular fibrosis may be severe enough to result in _____. Although it usually is asymptomatic, nonspecific electrocardiographic changes are most common.
AR or MS
Lyme disease is caused by a tick-borne spirochete _____. It usually begins during the summer months with a characteristic rash _____, followed by acute neurologic, joint, or cardiac involvement, usually with few long-term sequelae.
Borrelia burgdorferi
Erythema chronicum migrans
Early studies indicated that up to 10% of untreated patients with Lyme disease demonstrated evidence of transient cardiac involvement, the most common manifestation being _____ of variable degree.
AV block of variable degree
An abnormal _____ scan is compatible with cardiac involvement, and the demonstration of spirochetes in myocardial biopsy specimens of patients with Lyme carditis suggests a direct cardiac effect.
Gallium scan
Patients with Lyme Carditis with second-degree or complete heart block should be hospitalized and undergo continuous electrocardiographic monitoring. _____ may be required for a week or longer in patients with a high-grade block
Temporary transvenous pacing
Intravenous antibiotics are suggested for Lyme carditis, although oral antibiotics can be used when only mild cardiac involvement is present.
_____ may reduce myocardial inflammation and edema, which in turn can shorten the duration of the heart block. It is thought that treatment of the early manifestations of the disease will prevent development of late complications.
Corticosteroids
Chagas disease is one of the major causes of _____ cardiomyopathy throughout the world, although the incidence is changing.
Nonischemic CMP
Symptoms from T. cruzi infection typically begin _____ weeks after a bite from an infected triatomine, or can occur up to a few months after transfusion of infected blood.
1-2 weeks
The parasite load with T. cruzi infection can affect the severity of clinical presentation.
The initial acute phase of the disease begins 1 to 2 weeks after infection and lasts for up to _____ weeks.
4-8 weeks
In the acute phase, the most sensitive diagnostic test is the identification of T. cruzi genetic material in the blood using _____. During the acute phase of parasite infection, most affected patients are either asymptomatic or have mild, subacute febrile illness. Other potential manifestations include adenopathy, hepatomegaly, myocarditis, and meningoencephalitis
PCR assay
Cardiovascular abnormalities during the acute phase of T. cruzi infection might include _____.
Nonspecific ECG changes
1st-degree AVB
Cardiomegaly on chest x-ray examination
In up to ____% of patients with acute Chagas Disease, the symptoms of disease resolve spontaneously, even without therapeutic intervention.
Of these, approximately 60% to 70% develop an intermediate form of the disease that is characterized by the _____ of signs or symptoms of cardiac or gastrointestinal involvement
90%
Absence
The other 30% to 40% of patients will develop manifestations of the chronic Chagas disease 5 to 15 years after the acute phases of the disease
Cardiac involvement in the _____ form of Chagas is characterized by myocardial fibrosis, destruction of the conduction system, ventricular dilation, thinning of the apex of the heart, and formation of a thrombus in the apex of the heart.
These changes lead to DCM, symptomatic heart failure, arrhythmias, atrioventricular and bundle branch block, and possible thromboembolism.
Chronic
_____, which both inhibit T. cruzi DNA replication,and are effective against the trypomastigote and amastigote forms of the parasite, are currently the only treatments for treating Chagas disease.
Benznidazole and nifurtimox
_____ is considered to be the first line of therapy because of its better tolerability in Chagas disease
Benznidazole
The _____ trial was a prospective study of 2854 patients with Chagas cardiomyopathy randomized to receive benznidazole or placebo for up to 80 days.The primary outcome variable was a clinical composite of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.
BENEFIT showed that although benznidazole significantly reduced the detection of parasite in the serum, it had no effect on the primary outcome (adjusted HR,0.92;95% CI, 0.81 to 1.06; p = 0.26).2
BENEFIT
The usual host of Echinococcus granulosus is the _____, but _____ may serve as intermediate hosts if they accidentally ingest ova from contaminated dog feces.
When cardiac involvement is present, the cysts usually are _____.
Usual Host: DOG
Intermediate host: Humans
Intramyocardial
Interventricular septum
LV free wall
A myocardial cyst (E granulosus) can _____.
Degenerate and calcify
Develop daughter cysts
Rupture
_____ is the most dreaded complication of hydatid cysts
Rupture of the cyst
Rupture into the pericardium can result in acute pericarditis, which may progress to chronic constrictive pericarditis.
Rupture into the cardiac chambers can result in systemic or pulmonary emboli.
Rapidly progressive ______ can occur with rupture of right-sided cysts, with subsequent embolization of hundreds of scolices, fragments of the tapeworm, into the pulmonary circulation
Pulmonary hypertension
The liberation of hydatid fluid into the circulation can produce profound, fatal circulatory collapse as a result of an _____ to the protein constituents of the fluid
Anaphylactic reaction
Chest pain in patients with Echinococcosis usually is due to ______.
Rupture of the cyst into the pericardial space with resultant pericarditis
In Echinococcosis, 2D echocardiography, computed tomography, or cardiac magnetic resonance (CMR) imaging may aid in the detection and localization of heart cysts.
_____, when present, is a useful adjunctive laboratory finding
Eosinophilia
In terms of therapy for Echinococcosis, despite the availability of effective drugs such as mebendazole and albendazole, _____ generally is recommended, even for asymptomatic patients.
This is because of the significant risk of rupture of the cyst and its attendant serious and sometimes fatal consequences.
Surgical excision
Infection with Trichinella spiralis is common after ingestion of infected meat, usually _____.
Pork
Trichinella spiralis typically infects _____.
Reports of the incidence of clinically detectable cardiac involvement average around 25% of infected patients worldwide
Skeletal muscle
_____ may develop in some patients and constitute the most common cause of death in Trichinosis
Cardiomyopathy and arrhythmias
In trichinosis, a prominent focal infiltrate composed primarily of _____ can be found, with occasional microthrombi in the intramural arterioles.
Areas of muscle degeneration and necrosis are present.
Eosinophils
The clinical myocarditis in trichinosis may be mild and go unnoticed, but in a subset of cases it is manifested by heart failure and chest pain, usually appearing around the _____ week of the disease.
3rd week
Electrocardiographic abnormalities in trichinosis are detected in approximately 20% of patients with trichinosis and parallel the time course of clinical cardiac involvement, initially appearing in the ____ week and usually resolving by the _____ week.
Appears at: 2nd - 3rd week
Resolves: 7th week
The most common electrocardiographic abnormalities in trichinosis are _____.
Repolarization abnormalities
VPCs
Treatment of trichinosis is with _____; dramatic improvement in cardiac function has been reported after completion of an appropriate regimen of these agents.
Anthelminthics and corticosteroids
Briefly, radiation therapy can lead to a variety of cardiac complications that arise long after the completion of the therapy, including _____.
(1) Pericarditis with effusion, tamponade, or constriction
(2) Coronary artery fibrosis and myocardial infarction
(3) Valvular abnormalities
(4) Myocardial fibrosis
(5) Conduction disturbance
Radiation-induced cardiac damage is related to the _____.
(1) Cumulative dose of the radiation
(2) Mass of heart irradiated.
The late cardiac damage that may follow irradiation appears to result from a long-lasting injury of the capillary endothelial cells, which leads to cell death, capillary rupture, and microthrombi.
Because of this damage to the microvasculature, _____ results and is followed by _____.
Ischemia
Myocardial fibrosis
In addition to microvascular damage in radiation exposure, the major epicardial coronary arteries can become narrowed, especially at the _____.
Ostia
Occasionally a patient will develop acute cardiac complications after radiation therapy.
This typically manifests as _____.
A mild, transient, _____ of left ventricular function is sometimes seen early after radiation therapy.
Acute pericarditis
Symptomatic depression
The more common clinical expressions of heart disease occur months or years after the exposure to radiation.
The ______ is the most common site of clinical involvement, with findings of _____.
Pericardium
Chronic pericardial effusion or pericardial constriction
Left and/or right ventricular dysfunction at rest or with exercise appears to be a common, albeit usually asymptomatic, finding _____ years after radiation therapy
5 to 20 years
_____ may be seen months or years after therapeutic radiation, although the ultimate clinical significance is unclear.
ECG abnormalities
Heart block
Accelerated atherosclerosis
Variety of arrhythmias
Heat stroke results from failure of the thermoregulatory center following exposure to a high ambient temperature.
It is manifested principally by _____.
Hyperpyrexia
Renal insufficiency
DIC
CNS dysfunction
In heat stroke, pathologic cardiac changes include _____.
Dilation of the right side of the heart, particularly the right atrium
Hemorrhages of the subendocardium and the subepicardium are frequently seen at necropsy and often involve the _____ in heat stroke
IVS and posterior wall of the LV
In heat stroke, sinus tachycardia is invariably present, whereas _____ arrhythmias usually are absent.
Atrial and ventricular arrhythmias - ABSENT
Transient prolongation of the QT interval may be seen, along with ST-segment and T wave abnormalities.
It can take up to several months for these repolarization abnormalities to resolve.
Clinical manifestations of hypothermia include _____.
Sinus bradycardia
Conduction disturbances
Atrial (and occasionally ventricular) fibrillation,
Hypotension
Fall in cardiac output
Reversible myocardial depression
Characteristic deflection of the terminal portion of the QRS pattern (Osborn wave)
Classically, patients with acute myocarditis present with ____ symptoms related to the heart.
Nonspecific symptoms
In a recent series of 245 patients with clinically suspected myocarditis, the most common symptoms included _____.
Fatigue (82%)
Dyspnea on exertion (81%)
Arrhythmias (55%, both SV and ventricular)
Palpitations (49%)
Chest pain at rest (26%)
The viral prodrome of _____ occurs in 20% to 80% of the cases of acute myocarditis and can be readily missed by the patient; thus, they cannot be relied on for a diagnosis.
Fever, chills, myalgias, and constitutional symptoms
Approximately _____% of patients with biopsy-proven myocarditis display fulminant myocarditis.
This entity is characterized by an abrupt onset, usually within 2 weeks of a viral illness.
10%
The echocardiogram in fulminant myocarditis reveals _____.
Diffuse global hypofunction
Cardiac dilation, (Rare)
Thickening of the ventricular wall, probably due to myocardial edema from myocardial inflammation and cytokine release.
Endomyocardial biopsy (EMB) in fulminant myocarditis reveals _____ myocarditis in virtually each histologic section, making it a reliable source of confirmation
Typical and diffuse
Endomyocardial biopsy in giant cell myocarditis reveals a distinctive pattern of _____.
Giant cells with active inflammation + scar tissue
Patients with giant cell myocarditis often have other autoimmune disorders including _____.
Thymoma and Crohn disease
Pathologic examination in chronic active myocarditis with a myocardial biopsy specimen may show active myocarditis, but more frequently it is only _____.
Borderline
or g
Generalized chronic myopathic changes with fibrosis and myocyte dropout
Some patients with chronic active myocarditis may progress to diastolic dysfunction with predominantly fibrosis; this condition ultimately resembles a _____ cardiomyopathy.
Restrictive CMP
This category encompasses 60% to 70% of patients with active or borderline myocarditis who present with DCM of unknown cause.
Chronic active myocarditis
_____ myocarditis is caused by a hypersensitivity reaction to a foreign antigen, almost always a drug
Allergic eosinophilic myocarditis
The heart may be inflamed in association with systemic eosinophilic disorders, resulting in myocardial, endocardial, and valvular involvement (“_____”)
Löffler endocarditis
Allergic eosinophilic myocarditis requires a high degree of suspicion (related to the initiation of new agents) and subtle declines in left ventricular function.
Withdrawal of the offending agent and administration of _____ usually result in resolution
Corticosteroids
Peripartum cardiomyopathy is characterized by the onset of left ventricular dysfunction in the _____, with no preexisting cardiac dysfunction and no recognized cause of the cardiomyopathy.
Last month of pregnancy or within 5 months of delivery
There is evidence that patients submitted to endomyocardial biopsy early after presentation have a high frequency of myocarditis.
Because most patients with PPCM recover with standard therapy, biopsy is recommended only for those with _____.
Persistent LV dysfunction and symptoms despite heart failure management
The presence of a QRS width greater than ____ milliseconds in duration and _____ is associated with a great risk of cardiac death or need for heart transplantation
QRS > 120 ms
Q waves
Pathognomonic ECG findings are lacking in acute myocarditis, but _____ are common.
_____ may accompany a clinical presentation of myopericarditis.
Nonspecific repolarization changes and sinus tachycardia
PR-segment depression and diffuse ST-segment elevation
In patients who have an acute cardiomyopathy ,the most common pattern is a _____ ventricle with ___ systolic function.
Dilated, spherical ventricle with reduced systolic function
Patients with heart failure due to fulminant myocarditis typically present with _____ cardiac chambers and mild and _____ ventricular hypertrophy from inflammation.
____ dysfunction is less common and heralds a poor prognosis
Small cardiac chambers
Reversible
RV dysfunction: Poor prognosis
A pericardial effusion usually signifies _____.
Myopericarditis
The _____ technique can quantitate regions of damage and possibly predict the risk of cardiovascular death and ventricular arrhythmias after myocarditis
T1-weighted, myocardial-delayed enhancement
T2- weighted imaging can be used to detect myocardial _____.
Edema
The sensitivity and specificity of CMR in suspected myocarditis more than 14 days after symptom onset were _____.
Poor (sensitivity, 63%; specificity, 40%)
Thus, CMR performs best in the setting of acute cardiomyopathy or chest pain with elevated troponin.
An _____ pattern of delayed enhancement is associated with greater risk of MACE as is an _____ in DGE on follow-up CMR 6 months after presentation
Anteroseptal pattern
Increase in DGE
A _____ in LGE on follow-up CMR is associated with a low risk of MACE
Decrease
The diagnostic accuracy of the Lake Louise Criteria ranges from _____%, depending on the number of tissue markers used in CMR studies
68% to 78%
Lake Louise Consensus Criteria Cardiac Magnetic Resonance Diagnosis of Myocarditis
In the setting of clinically suspected myocarditis,* CMR findings are consistent with myocardial inflammation, if at least two of the following criteria are present:
1. Regional or global myocardial SI increase in T2-weighted images.†
2. Increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1- weighted images.‡
3. There is at least one focal lesion with nonischemic regional distribution in IR-prepared gadolinium-enhanced T1-weighted images(“late gadolinium enhancement”).§A CMR study is consistent with myocyte injury and/or scar caused by myocardial inflammation, if criterion 3 is present
A repeat CMR study between 1 and 2 weeks after the initial CMR study is recommended, if
none of the criteria are present, but the onset of symptoms has been very recent and there is strong clinical evidence for myocardial inflammation.
- one criteria is present
The presence of LV dysfunction or pericardial effusion provides additional, supportive evidence for myocarditis.
The rate of major complications with EMB is less than _____ in 1000 when the procedure is done by experienced operators
<1 in 1000
The clinical scenarios in which EMB is most useful are _____.
Supected GCM and fulminant lymphocytic myocarditis in the setting of an acute cardiomyopathy
_____ should be considered in acute DCM that fails to respond to usual care or is complicated by high-grade heart block or sustained ventricular tachycardia
GCM
Histologically, GCM is defined by a _____.
Diffuse or multifocal inflammatory infiltrate of lymphocytes and multinucleated giant cells
+
Absence of granuloma
In contrast with cardiac sarcoidosis, in which the giant cells are located _____, the giant cells often are located at the ____ of the inflammation, where myocyte damage is present
Cardiac sarcoidosis: within the granuloma
GCM: Edges of the inflammation
Algorithm for the evaluation of suspected myocarditis in the setting of unexplained acute cardiomyopathy.
If with the following:
Requiring inotropic support
Mobitz type 2 or higher HB
Sustained or symptomatic VT
Faiulre to respond to GDMT within 1-2 weeks
Yes»> Class I EMB
No»_space; Class 2b CMR
The presence of _____ on EMB may portend a poor outcome.
Viral genomes
The first-line therapy for all patients with myocarditis and heart failure is _____.
Supportive care
Treatment of _____ may be helpful in the management of posttransplantation viral heart disease in children.
However, in adult patients with chronic DCM and viral genomes detected by PCR in heart biopsy tissues, one trial series suggests that _____ improves enteroviral or adenoviral heart infection
Viral infection
6 mIU of IFN-gamma three times per week
There may be a role for a short course of immunosuppression in patients with chronic DCM who fail to respond to guideline-based heart failure management. In the _____ trial, patients with chronic inflammatory cardiomyopathy without persistent viral infection were randomly assigned to receive either prednisone and azathioprine or placebo. Immunosuppressive treatment was associated with an increase in the left ventricular ejection fraction from 26% to 46% and an improved quality of life, whereas none of the patients in the placebo arm improved their left ventricular ejection fraction
Tailored Immunosuppression in Inflammatory Cardiomyopathy (TIMIC)
