After exiting from Epworth Hospital, I purchased a Fitbit HR wrist monitor. Checked it against a cuff BP and heart rate monitor. Good enough. Pulse rate all over the place. easy to send it to 112 with eating big meal including bread and marmelade. After been given a prawn at Mabel's house , noticed the pulse rate was lowered after 30 minutes to 71. Very interesting, suggestive of needed amino acid or other factor or maybe tie up to Cocca allergy , but then saw work on glycine and that cascade of links to cardiovascular thinking and liver lipid metabolism.
Cardiac Troponin
Sunday 31 May 2015
Thursday 21 May 2015
Myocarditis
MAy 21st
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A significant minority of patients with pericarditis also have myocarditis. Myocarditis associated with pericarditis, including vaccinia-associated disease (myocarditis and/or pericarditis), is discussed separately. (See "Myopericarditis".)
In hospital- or clinic-based referral populations, the prognosis of myocarditis varies with the type or cause and the severity of presenting symptoms [2]. In the majority of asymptomatic patients who develop inflammation as evidenced by electrocardiographic changes, the inflammatory process is apparently self-limited without short-term, overt sequelae. A minority of initially asymptomatic patients develop heart failure (HF), serious arrhythmias, or disturbances of conduction. Rarely, post-viral myocarditis is fatal due to myocardial failure or sudden, unexpected death [3].
In contrast, most patients with symptomatic post-viral or lymphocytic myocarditis present with HF and dilated cardiomyopathy (DCM). However, subtle signs and symptoms of cardiac involvement may be overshadowed by systemic manifestations of the viral infection. As an example, in the United States Myocarditis Treatment Trial, 89 percent of subjects reported a syndrome consistent with a viral prodrome [4].
Myocarditis is a cause of ventricular and atrial arrhythmias. Although only a small fraction of patients with lymphocytic myocarditis present with ventricular arrhythmias, as many as one-third of patients diagnosed with idiopathic ventricular tachycardia may have myocarditis [5-7]. Myocarditis also causes some cases of atrial fibrillation [8,9].
In a significant minority of patients with acute myocarditis, impaired ventricular function, arrhythmias, and/or disturbances of conduction may persist for months to years; this can be due to residual scar tissue, persistent active myocarditis, or occasionally persistent viral infection [10-12]. In a review of 1230 patients with initially unexplained cardiomyopathy, 9 percent had myocarditis [2]. (See "Causes of dilated cardiomyopathy".)
Predictors of adverse outcome in acute myocarditis include severity of left ventricular or biventricular dysfunction [17,18]. In a series of 109 cases with Dallas criteria positive (active or borderline) myocarditis, findings at presentation that were predictive of subsequent death or transplantation were syncope (relative risk 8.5), bundle branch block (relative risk 2.9), and an LVEF <40 percent (relative risk 2.9) [17]. Although borderline histology was protective, this was not seen in other series [16,19]. In a prospective study on 174 patients with biopsy-proven myocarditis, presence of signs and symptoms of biventricular dysfunction was the main predictor of death or heart transplantation [18].
Another adverse prognostic factor is the development of secondary pulmonary hypertension. This was illustrated in a prospective study of 1134 patients with a new cardiomyopathy who underwent right heart catheterization and EMB and were followed for 4.4 years [20]. In a multivariate model, mean pulmonary artery pressure was the most important hemodynamic predictor of death, especially in the 93 patients (8.3 percent) with a diagnosis of myocarditis. For each 5 mmHg increase in baseline mean pulmonary artery pressure, the mortality in those with and without myocarditis increased with a relative hazard of 1.85 and 1.23, respectively.
However, other case series in which parvovirus B19 was the most frequent pathogen have not demonstrated an effect of viral genome on the risk of death or heart transplantation, raising a possibility that viral genomes may sometimes reflect latent and not active viral infection [24].
Although these data suggest that persistence of viral genome may predict a gradual deterioration of left ventricular function in chronic DCM, a clinical role for EMB in the management of such patients will depend upon more definitive evidence of effective treatment of viral cardiomyopathy.
Further support for the role of Fas comes from a study of 20 patients with recent-onset idiopathic DCM [26]. The patients in the highest tertile of Fas expression in the myocardium had minimal improvement in LVEF at six months compared to those in the intermediate and lowest tertiles (3 versus 10 and 21 percent, respectively).
A higher serum IL-10 concentration on admission may be predictive of cardiogenic shock and death in patients with fulminant (predominantly lymphocytic) myocarditis [27].
Treatment with a combination of immunosuppressive agents may improve prognosis [29,30]. A report from Helsinki of 32 patients with GCM (including 26 patients treated with combined immunosuppression [two to four drugs]) found survival rates similar to those previously reported for lymphocytic myocarditis [30]. The Kaplan-Meier estimates of transplant–free survival from symptom onset were 69 percent at one year, 58 percent at two years, and 52 percent at five years. The risk of ventricular arrhythmias was high. Of the transplant-free survivors, 10 of 17 experienced sustained ventricular tachycardia during follow-up with three receiving appropriate implantable cardioverter-defibrillator shocks. (See 'Giant cell myocarditis' below.)
Treatment in hemodynamically stable patients includes diuresis as needed, and early initiation of angiotensin converting enzyme inhibitor (or angiotensin receptor blocker). In stable patients with systolic HF, treatment includes an evidence-based beta blocker (carvedilol, extended release metoprolol, and bisoprolol) with addition of mineralocorticoid receptor antagonist in patients with symptomatic HF with left ventricular ejection fraction <35 percent (with exclusions for patients at risk for hyperkalemia) (figure 4). (See "Overview of the therapy of heart failure due to systolic dysfunction".)
Angiotensin converting enzyme inhibitor and beta blocker therapy may have specific benefits in patients with myocarditis, in addition to their proven benefits in reducing morbidity and mortality in patients with systolic HF generally. A study in murine coxsackievirus myocarditis showed that captopril administration on day three led to less myonecrosis and dystrophic calcification, suggesting benefits by mechanisms other than vasodilatation [37]. In a murine model of coxsackievirus myocarditis, treatment with a nonselective beta blocker improved outcome [38]. (See "Overview of the therapy of heart failure due to systolic dysfunction" and "ACE inhibitors in heart failure due to systolic dysfunction: Therapeutic use" and "Use of beta blockers in heart failure due to systolic dysfunction".)
Although digoxin provides symptomatic benefit in patients with systolic HF generally, its efficacy and safety in patients with myocarditis is uncertain. Digoxin increased mortality in a mouse model of viral myocarditis [39]. Since the effects of digoxin in acute clinical myocarditis are uncertain, we avoid its use in this setting [40]. (See "Use of digoxin in heart failure due to systolic dysfunction".)
Mechanical circulatory support with a VAD should be considered when HF is intractable or when cardiogenic shock does not respond to medical therapy [41,42]. Several reports suggest that in some patients, these devices can be used successfully as a bridge to spontaneous recovery in the setting of fulminant myocarditis. Among patients with fulminant myocarditis with cardiogenic shock treated with a VAD, a more rapid initial course is associated with greater likelihood of recovery. In a series of 24 patients implanted with VADs for fulminant myocarditis, patients who recovered had a more acute initial decompensation (ie, 7 versus 22 days from onset of symptoms to VAD implantation) than those who required heart transplantation [43]. Similarly, in a case series of 373 patients with recent onset nonischemic cardiomyopathy, presence of myocarditis was the strongest predictor of bridge to recovery [44].
Candidacy for cardiac transplantation should be considered in patients with chronic myocarditis presenting as an intractable cardiomyopathy with refractory HF. Although a case series of 12 patients with active lymphocytic myocarditis at the time of transplant suggested an increased surgical risk in such patients [45], patients with biopsy-proven myocarditis (n = 142) in the much larger United Network for Organ Sharing registry did at least as well as other cardiac transplantation patients over one-year follow-up [46]. (See "Prognosis after cardiac transplantation".)
When mechanical circulatory support is anticipated, a diagnosis of giant cell myocarditis (GCM) may lead to use of a biventricular device because of the likelihood of progressive right ventricular failure and to an early heart transplant listing. Transplantation is an effective therapy for GCM. Among 34 patients who underwent transplantation for this disease, recurrence was documented in nine after an average follow-up of three years [47]. Post-transplantation survival was 71 percent at three years despite a 25 percent rate of histologic recurrence on post-transplant endomyocardial biopsy.
Our suggested approach is in broad agreement with major society guidelines [48]:
Preliminary data suggest that antiviral therapy with interferon beta may be beneficial for patients with chronic dilated cardiomyopathy (DCM) and evidence of viral genome in endomyocardial biopsy (EMB) specimens by the polymerase chain reaction (PCR). In the randomized controlled multicenter Beta Interferon for Chronic Cardiomyopathy trial, 143 patients with DCM with evidence of myocarditis and confirmed myocardial viral infection were randomly assigned to interferon beta or placebo; preliminary results were presented in abstract form [61]. Treatment with beta interferon significantly reduced myocardial viral load but virus (particularly parvovirus B19) persisted in some patients [62]. Beta interferon improved patient global assessment compared to placebo at 24 weeks and improved New York Heart Association functional class compared to placebo at 12 weeks but not at 24 weeks [61].
A systematic review including eight randomized controlled trials found that glucocorticoid therapy did not reduce mortality or improve functional status in patients with viral myocarditis, though improvement in left ventricular ejection fraction (LVEF) was suggested [67]. Although some observational, mostly uncontrolled, clinical studies have suggested clinical benefit from combination immunosuppressive therapy with glucocorticoids, azathioprine, or cyclosporine [68-70], evaluation of true effectiveness is difficult in myocarditis because of the high rate of spontaneous recovery [71,72].
No benefit from immunosuppressive therapy was found in acute myocarditis of unspecified etiology. In the randomized, controlled trial Myocarditis Treatment Trial, 111 patients with a histopathologic diagnosis of myocarditis of unspecified etiology and an LVEF of less than 45 percent were randomly assigned to receive conventional therapy alone or immunosuppression with either cyclosporine or azathioprine for 28 weeks [4]. In all patients, the LVEF improved from 25 to 34 percent and the mortality rate was 20 percent at one year and 56 percent at 4.3 years. There was no difference in outcome in the two treatment groups. A more robust inflammatory response was associated with less severe disease and a greater improvement in cardiac function.
In contrast to the lack of benefit seen in acute myocarditis of unspecified etiology, patients with chronic myocardial inflammation may respond to immunomodulatory therapy, as suggested by two randomized controlled trials:
A possible relationship between responsiveness to immunosuppressive therapy and presence of cardiac autoantibodies was suggested by an uncontrolled study of 41 patients with progressive HF for six months or more who were unresponsive to standard therapy and who had active lymphocytic myocarditis on biopsy [23]. All 41 were treated with prednisone and azathioprine. The following findings were noted:
Limited data are available on the use of immunosuppressive therapy of lymphocytic myocarditis in the setting of unexplained ventricular arrhythmias. In one study, 17 of 65 patients had unexplained ventricular arrhythmias in the apparent absence of structural heart disease [81]. Twelve of these patients underwent EMB and six had evidence of lymphocytic myocarditis. These six patients were treated with prednisone and azathioprine; none had recurrent spontaneous arrhythmias and none had ventricular arrhythmias that could be induced by electrophysiologic stimulation despite cessation of antiarrhythmic medications. Since data are limited, the indications for and value of detection of myocarditis in this setting are controversial. (See "Endomyocardial biopsy", section on 'Unexplained arrhythmias'.)
The randomized controlled IMAC trial of 62 patients with recent-onset (≤6 months of symptoms) DCM with LVEF ≤40 percent found that the improvement in LV function was the same with IVIG (1 g/kg per day for two days) and placebo [71]. Eleven percent of patients had "Dallas criteria" positive myocarditis. At one year, both groups of patients did well as the LVEF rose from 25 percent at baseline to 42 percent. Thirty-six percent had a normal LVEF, and the transplant-free survival at one and two years was 92 and 88 percent. [71].
In contrast, in a randomized, placebo-controlled trial of 40 patients with chronic DCM of unspecified etiology, IVIG significantly improved LVEF, while no improvement in LVEF was seen with placebo [83].
Disclosures: Leslie T Cooper, Jr, MD Nothing to disclose. William J McKenna, MD Nothing to disclose. Susan B Yeon, MD, JD, FACC Nothing to disclose.
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Treatment and prognosis of myocarditis in adults
Author
Leslie T Cooper, Jr, MD
Leslie T Cooper, Jr, MD
Section Editor
William J McKenna, MD
William J McKenna, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC
Susan B Yeon, MD, JD, FACC
All topics are updated as new evidence becomes
available and our peer review process is complete.
Literature review current
through: Apr 2015. | This topic last
updated: May 11, 2015.
INTRODUCTION — Myocarditis refers to inflammation of the heart
muscle. The diagnosis may be suspected by clinical and noninvasive features and
is confirmed by histopathologic criteria on endomyocardial biopsy. The clinical
manifestations of this disorder vary greatly from asymptomatic changes on an
electrocardiogram to fulminant heart failure (HF). (See "Clinical manifestations
and diagnosis of myocarditis in adults".)
This topic will review the prognosis and treatment of myocarditis in adults.
Treatment of myocarditis consists of both specific therapy aimed at the cause of
the myocarditis and nonspecific therapy aimed at the clinical manifestations
such as HF and arrhythmias. The etiology, incidence, pathogenesis, clinical
manifestations, and diagnosis of myocarditis are discussed separately. (See
"Etiology and pathogenesis of myocarditis" and "Clinical manifestations and
diagnosis of myocarditis in adults".) A significant minority of patients with pericarditis also have myocarditis. Myocarditis associated with pericarditis, including vaccinia-associated disease (myocarditis and/or pericarditis), is discussed separately. (See "Myopericarditis".)
NATURAL HISTORY AND
PROGNOSIS
Variable disease
course — Limited data are available on
the natural history and prognosis of myocarditis because there is no widely
available noninvasive diagnostic test to confirm the diagnosis, and
endomyocardial biopsy (EMB) is not performed in many suspected cases. The
available evidence suggests that the prognosis in adults with myocarditis varies
widely.
The prevalence and outcomes of myocarditis in community-based populations are
unknown. However, seroepidemiologic studies suggest that the majority of cases
of Coxsackie B virus infection are subclinical and have a benign course [1].In hospital- or clinic-based referral populations, the prognosis of myocarditis varies with the type or cause and the severity of presenting symptoms [2]. In the majority of asymptomatic patients who develop inflammation as evidenced by electrocardiographic changes, the inflammatory process is apparently self-limited without short-term, overt sequelae. A minority of initially asymptomatic patients develop heart failure (HF), serious arrhythmias, or disturbances of conduction. Rarely, post-viral myocarditis is fatal due to myocardial failure or sudden, unexpected death [3].
In contrast, most patients with symptomatic post-viral or lymphocytic myocarditis present with HF and dilated cardiomyopathy (DCM). However, subtle signs and symptoms of cardiac involvement may be overshadowed by systemic manifestations of the viral infection. As an example, in the United States Myocarditis Treatment Trial, 89 percent of subjects reported a syndrome consistent with a viral prodrome [4].
Myocarditis is a cause of ventricular and atrial arrhythmias. Although only a small fraction of patients with lymphocytic myocarditis present with ventricular arrhythmias, as many as one-third of patients diagnosed with idiopathic ventricular tachycardia may have myocarditis [5-7]. Myocarditis also causes some cases of atrial fibrillation [8,9].
In a significant minority of patients with acute myocarditis, impaired ventricular function, arrhythmias, and/or disturbances of conduction may persist for months to years; this can be due to residual scar tissue, persistent active myocarditis, or occasionally persistent viral infection [10-12]. In a review of 1230 patients with initially unexplained cardiomyopathy, 9 percent had myocarditis [2]. (See "Causes of dilated cardiomyopathy".)
Predictive value of
autoantibodies — Cardiac-specific
autoantibodies have been identified in subsets of patients with acute or chronic
myocarditis [13-15]
and appear to be associated with a worse prognosis in patients with chronic
myocarditis and a better prognosis in patients with acute myocarditis. Presence
of autoantibodies was associated with increased risk of progression from chronic
myocarditis to DCM (figure 1) [14].
As an example, the presence of anti-alpha myosin autoantibodies was associated
with lower likelihood of improvement in left ventricular systolic and diastolic
function in a series of 33 patients with chronic myocarditis [14].
Patients with antibodies had no improvement in left ventricular ejection
fraction (LVEF) at six months compared to a 9 percent absolute increase in those
without antibodies. Similarly, the presence of anti-heart antibodies in
relatives of patients with idiopathic DCM predicted future left ventricular
dilation [15].
In contrast, in patients with acute myocarditis, higher titers of IgG were
associated with better left ventricular function in the Myocarditis Treatment
Trial [4].
One possible explantation is that the acute immune response to viral infection
usually serves to eliminate the pathogen and improve heart function, but in
genetically susceptible patients, autoimmunity is induced, leading to
progression to chronic DCM. (See "Etiology and pathogenesis of myocarditis",
section on 'Autoimmune mechanisms'.)
Prognosis based on
etiology — The available data suggest
that prognosis of myocarditis likely varies among clinicopathologic types. (See
"Clinical manifestations and diagnosis of myocarditis in adults", section on
'Clinicopathologic classification'.)
Lymphocytic myocarditis
Spectrum of
disease — Lymphocytic myocarditis has a
variable course, including the following presentations:
●Some patients have subclinical
disease
●Some have indolent disease that
progresses to DCM
●Others present with fulminant
disease that may be fatal or may fully resolve after acute hemodynamic
support
In one report of 27 patients (mean age 47) with myocardial biopsy-proven
definite or borderline myocarditis, the five-year survival was 56 percent,
similar to that in a comparison cohort of patients with idiopathic DCM without
myocarditis (figure 2) [16].Predictors of adverse outcome in acute myocarditis include severity of left ventricular or biventricular dysfunction [17,18]. In a series of 109 cases with Dallas criteria positive (active or borderline) myocarditis, findings at presentation that were predictive of subsequent death or transplantation were syncope (relative risk 8.5), bundle branch block (relative risk 2.9), and an LVEF <40 percent (relative risk 2.9) [17]. Although borderline histology was protective, this was not seen in other series [16,19]. In a prospective study on 174 patients with biopsy-proven myocarditis, presence of signs and symptoms of biventricular dysfunction was the main predictor of death or heart transplantation [18].
Another adverse prognostic factor is the development of secondary pulmonary hypertension. This was illustrated in a prospective study of 1134 patients with a new cardiomyopathy who underwent right heart catheterization and EMB and were followed for 4.4 years [20]. In a multivariate model, mean pulmonary artery pressure was the most important hemodynamic predictor of death, especially in the 93 patients (8.3 percent) with a diagnosis of myocarditis. For each 5 mmHg increase in baseline mean pulmonary artery pressure, the mortality in those with and without myocarditis increased with a relative hazard of 1.85 and 1.23, respectively.
Fulminant myocarditis — Patients who present with fulminant lymphocytic
myocarditis (ie, those presenting with acute HF with severe hemodynamic
compromse), although more severely ill, may be more likely to fully recover than
those with acute myocarditis if they survive the acute phase of the disease [19,21].
This hypothesis was examined in a study of 147 patients (age >15 years) with
biopsy-proven myocarditis, 15 of whom had fulminant myocarditis based upon
presenting clinical features, which included severe hemodynamic compromise,
rapid onset of symptoms, and fever [19].
After an 11-year follow-up, survival free of transplant was significantly better
in those with fulminant myocarditis (93 versus 45 percent for acute or
borderline myocarditis) (figure 3). After adjusting for age, hemodynamic
variables, and histopathologic variables, fulminant myocarditis was an
independent predictor of survival.
Persistence of viral
genome — An important predictor of
outcome in patients with viral myocarditis may be the persistence of the viral
genome in the myocardium. This was suggested in a consecutive series of 172
patients with biopsy-proven viral infection; the patients had a relatively long
duration of symptoms (5.1 months) before the initial EMB and were already on a
reasonable HF regimen [22].
Among the 151 patients with a single infection (most frequently enterovirus),
follow-up biopsy at a median of 6.8 months revealed spontaneous clearance of the
viral genome in 55 (36 percent). These patients had a significant increase in
LVEF (from 50 to 58 percent), while those with persisting viral genomes had a
significant reduction in LVEF (from 54 to 51 percent).
Persistence of viral genome may also identify patients particularly unlikely
to respond to immunosuppressive therapy [23].
(See 'Immunosuppressive therapy' below.)However, other case series in which parvovirus B19 was the most frequent pathogen have not demonstrated an effect of viral genome on the risk of death or heart transplantation, raising a possibility that viral genomes may sometimes reflect latent and not active viral infection [24].
Although these data suggest that persistence of viral genome may predict a gradual deterioration of left ventricular function in chronic DCM, a clinical role for EMB in the management of such patients will depend upon more definitive evidence of effective treatment of viral cardiomyopathy.
Predictive value of serologic
markers — Although clinical parameters
are only partly predictive of outcome, serologic markers, particularly soluble
Fas ligand (FasL) and interleukin (IL)-10, may be useful in acute, severe
myocarditis. Fas (CD95), a member of the tumor necrosis factor receptor family,
is expressed following B-cell activation. Binding of Fas with its natural ligand
(FasL, which is expressed on activated T-cells) triggers apoptotic cell death.
As a result, Fas regulates clonal expansion of autoreactive B-cells.
In one series, serum concentrations of soluble Fas and FasL were
significantly higher in patients with acute myocarditis (predominantly
lymphocytic) compared to normals or patients with an old myocardial infarction
[25].
Among the patients with myocarditis, Fas and FasL concentrations were
significantly higher in those who died during hospitalization compared to those
discharged from the hospital after recovery.Further support for the role of Fas comes from a study of 20 patients with recent-onset idiopathic DCM [26]. The patients in the highest tertile of Fas expression in the myocardium had minimal improvement in LVEF at six months compared to those in the intermediate and lowest tertiles (3 versus 10 and 21 percent, respectively).
A higher serum IL-10 concentration on admission may be predictive of cardiogenic shock and death in patients with fulminant (predominantly lymphocytic) myocarditis [27].
Overlap with recent-onset
idiopathic dilated cardiomyopathy — Some patients presenting with recent-onset (≤6
months) idiopathic DCM have myocarditis. The prognosis in patients with
recent-onset idiopathic DCM may be fairly good. In a multicenter registry of 377
patients with acute DCM who received contemporary HF treatment and an average
baseline LVEF of 24 percent at entry, LVEF improved to 40 percent at six months
[28].
Transplant-free survival at one, two, and four years was 94, 92, and 88 percent,
respectively.
Giant cell myocarditis — Idiopathic giant cell myocarditis (GCM) is a rare
and frequently fatal type of myocarditis. In contrast to the variable clinical
course of DCM due to lymphocytic myocarditis, the clinical course in GCM is
usually characterized by acute or fulminant deterioration in left ventricular
systolic function despite standard HF treatment, frequent ventricular
arrhythmias, and heart block.
The prognosis of GCM with no or limited immunosuppressive therapy is poor. In
a study published in 1997 based on international case reports of 63 patients
with GCM, the presenting symptoms were HF (75 percent), ventricular arrhythmias
(14 percent), and heart block (5 percent) [29].
Initial symptoms resembling an acute myocardial infarction were present in 6
percent. The rate of death or cardiac transplant was 89 percent and the median
survival from onset of symptoms was 5.5 months. This represents a significantly
worse prognosis compared to lymphocytic or presumed viral myocarditis. As an
example, in the Myocarditis Treatment Trial, approximately 50 percent of
patients with lymphocytic myocarditis were alive without cardiac transplant at
five years [4].
Treatment with a combination of immunosuppressive agents may improve prognosis [29,30]. A report from Helsinki of 32 patients with GCM (including 26 patients treated with combined immunosuppression [two to four drugs]) found survival rates similar to those previously reported for lymphocytic myocarditis [30]. The Kaplan-Meier estimates of transplant–free survival from symptom onset were 69 percent at one year, 58 percent at two years, and 52 percent at five years. The risk of ventricular arrhythmias was high. Of the transplant-free survivors, 10 of 17 experienced sustained ventricular tachycardia during follow-up with three receiving appropriate implantable cardioverter-defibrillator shocks. (See 'Giant cell myocarditis' below.)
Eosinophilic
myocarditis — Myocarditis characterized
by a predominantly eosinophilic infiltrate may occur in association with
malignancy, parasite infection, hypersensitivity myocarditis (HSM),
endomyocardial fibrosis, and with the idiopathic hypereosinophilic syndrome.
(See "Etiology and pathogenesis of myocarditis", section on 'Hypersensitivity
myocarditis'.)
●HSM presents as sudden death or
rapidly progressive HF sometimes with rash, fever, and peripheral eosinophilia.
Necrotizing eosinophilic myocarditis has an exceptionally poor prognosis with
most cases diagnosed at autopsy.
●In contrast, eosinophilic
myocarditis associated with the hypereosinophilic syndrome typically evolves
over weeks to months. The presentation is usually biventricular HF, although
arrhythmias may lead to sudden death [31].
(See "Clinical manifestations, pathophysiology, and diagnosis of the
hypereosinophilic syndromes".)
Celiac disease — Limited data suggest a risk of progression with
HF and arrhythmias in untreated patients with myocarditis or DCM associated with
celiac disease. Case reports have described celiac disease, often clinically
unsuspected, associated with myocarditis or DCM [32-34].
In one series of nine patients with celiac disease and autoimmune myocarditis,
none had classic gastrointestinal symptoms of celiac disease (recurrent
abdominal pain, diarrhea, and weight loss), but all had iron deficiency anemia
refractory to iron replacement [32].
Cardiac
sarcoidosis — The prognosis of cardiac
sarcoidosis is worse in patients with cardiac symptoms and signs as discussed
separately. (See "Cardiac sarcoidosis", section on 'Prognosis'.)
MANAGEMENT — Treatment of myocarditis includes general
measures common to patients with various types of myocarditis or cardiomyopathy
as well as therapy targeting specific disorders.
General
management — Treatment of myocarditis
includes nonspecific measures to treat the sequelae of heart disease, including
heart failure (HF) therapy and treatment of arrhythmias according to current
guidelines, and in select cases, anticoagulation. Our approach is generally
similar to that in the European Society of Cardiology Working Group on
Myocardial and Pericardial Diseases position statement [35].
Heart failure
therapy — Patients with myocarditis
with HF should receive standard therapy for acute and chronic HF, depending upon
the clinical presentation. (See "Treatment of acute decompensated heart failure:
General considerations" and "Treatment of acute decompensated heart failure:
Components of therapy" and "Overview of the therapy of heart failure due to
systolic dysfunction".)
Agents — Oxygen administration is recommended to treat
hypoxia and may impact myocarditis since hypoxia aggravates experimental viral
myocarditis [36].
(See "Treatment of acute decompensated heart failure: Components of therapy",
section on 'Supplemental oxygen and assisted ventilation'.)
Beta blocker therapy is avoided with acute decompensated HF. (See
"Circulatory assist devices: Cardiopulmonary assist device and short-term left
ventricular assist devices" and "Intermediate- and long-term mechanical
circulatory support" and "Extracorporeal membrane oxygenation (ECMO) in
adults".)Treatment in hemodynamically stable patients includes diuresis as needed, and early initiation of angiotensin converting enzyme inhibitor (or angiotensin receptor blocker). In stable patients with systolic HF, treatment includes an evidence-based beta blocker (carvedilol, extended release metoprolol, and bisoprolol) with addition of mineralocorticoid receptor antagonist in patients with symptomatic HF with left ventricular ejection fraction <35 percent (with exclusions for patients at risk for hyperkalemia) (figure 4). (See "Overview of the therapy of heart failure due to systolic dysfunction".)
Angiotensin converting enzyme inhibitor and beta blocker therapy may have specific benefits in patients with myocarditis, in addition to their proven benefits in reducing morbidity and mortality in patients with systolic HF generally. A study in murine coxsackievirus myocarditis showed that captopril administration on day three led to less myonecrosis and dystrophic calcification, suggesting benefits by mechanisms other than vasodilatation [37]. In a murine model of coxsackievirus myocarditis, treatment with a nonselective beta blocker improved outcome [38]. (See "Overview of the therapy of heart failure due to systolic dysfunction" and "ACE inhibitors in heart failure due to systolic dysfunction: Therapeutic use" and "Use of beta blockers in heart failure due to systolic dysfunction".)
Although digoxin provides symptomatic benefit in patients with systolic HF generally, its efficacy and safety in patients with myocarditis is uncertain. Digoxin increased mortality in a mouse model of viral myocarditis [39]. Since the effects of digoxin in acute clinical myocarditis are uncertain, we avoid its use in this setting [40]. (See "Use of digoxin in heart failure due to systolic dysfunction".)
Mechanical circulatory
support and transplantation — Potential
options for patients with refractory HF despite optimum medical therapy include
mechanical circulatory support and cardiac transplantation. (See "Intermediate-
and long-term mechanical circulatory support" and "Practical management of
long-term mechanical circulatory support devices" and "Indications and
contraindications for cardiac transplantation".)
Hemodynamically unstable patients with HF may require mechanical circulatory
support (eg, ventricular assist device [VAD]) or extracorporeal membrane
oxygenation. Mechanical circulatory support with a VAD should be considered when HF is intractable or when cardiogenic shock does not respond to medical therapy [41,42]. Several reports suggest that in some patients, these devices can be used successfully as a bridge to spontaneous recovery in the setting of fulminant myocarditis. Among patients with fulminant myocarditis with cardiogenic shock treated with a VAD, a more rapid initial course is associated with greater likelihood of recovery. In a series of 24 patients implanted with VADs for fulminant myocarditis, patients who recovered had a more acute initial decompensation (ie, 7 versus 22 days from onset of symptoms to VAD implantation) than those who required heart transplantation [43]. Similarly, in a case series of 373 patients with recent onset nonischemic cardiomyopathy, presence of myocarditis was the strongest predictor of bridge to recovery [44].
Candidacy for cardiac transplantation should be considered in patients with chronic myocarditis presenting as an intractable cardiomyopathy with refractory HF. Although a case series of 12 patients with active lymphocytic myocarditis at the time of transplant suggested an increased surgical risk in such patients [45], patients with biopsy-proven myocarditis (n = 142) in the much larger United Network for Organ Sharing registry did at least as well as other cardiac transplantation patients over one-year follow-up [46]. (See "Prognosis after cardiac transplantation".)
When mechanical circulatory support is anticipated, a diagnosis of giant cell myocarditis (GCM) may lead to use of a biventricular device because of the likelihood of progressive right ventricular failure and to an early heart transplant listing. Transplantation is an effective therapy for GCM. Among 34 patients who underwent transplantation for this disease, recurrence was documented in nine after an average follow-up of three years [47]. Post-transplantation survival was 71 percent at three years despite a 25 percent rate of histologic recurrence on post-transplant endomyocardial biopsy.
Arrhythmias — Patients with myocarditis can develop both tachy-
and bradyarrhythmias. Because these arrhythmias often resolve after the acute
phase of myocarditis, therapy is generally supportive.
Electrocardiographic monitoring can permit early detection of asymptomatic
yet potentially life-threatening arrhythmias and/or
conduction defects. For this reason, it is recommended that patients with acute
and often unstable myocarditis be admitted to the hospital.Our suggested approach is in broad agreement with major society guidelines [48]:
●Antiarrhythmic therapy should
not be given for asymptomatic atrial and ventricular premature beats or for
asymptomatic nonsustained arrhythmias. (See "Supraventricular premature beats"
and "Ventricular premature beats" and "Management of nonsustained ventricular
tachycardia".)
●When antiarrhythmic therapy is
necessary (as indicated below), options include amiodarone, dofetilide (with
precautions for potential proarrhythmia), and in patients without class IV HF,
cautious use of beta blockers or calcium channel blockers. Due to the
proarrhythmic and negative inotropic effects, other class I and III
antiarrhythmic drugs are generally avoided in patients with acute
myocarditis.
●Supraventricular tachycardias
(SVTs) can induce or aggravate HF. For sustained, symptomatic SVT, restoration
of sinus rhythm is the recommended initial approach. For recurrent sustained
SVT, options include rate control therapy and antiarrhythmic therapy. The
specific approach to restoring sinus rhythm, controlling the ventricular rate,
and selecting an antiarrhythmic drug depends upon the arrhythmia and the overall
clinical scenario. (See "Overview of the acute management of
tachyarrhythmias".)
●For ventricular
arrhythmias:
•Symptomatic nonsustained
ventricular tachycardia can be treated with antiarrhythmic drugs. (See
"Management of nonsustained ventricular tachycardia".)
•Sustained ventricular
arrhythmias should be treated with urgent cardioversion, and recurrent
arrhythmias should be treated with antiarrhythmic drugs. (See "Secondary
prevention of sudden cardiac death in heart failure and cardiomyopathy".)
•Role of implantable
cardioverter-defibrillator (ICD) therapy:
-ICD implantation is generally
deferred in patients with acute myocarditis since myocarditis and arrhythmia
risk may resolve. A potential role for a wearable cardioverter-defibrillator for
patients at risk for sudden cardiac arrest has been suggested but the evidence
to support such therapy is scant [49].
-ICD implantation can be
beneficial in patients with life-threatening ventricular arrhythmias who are not
in the acute phase of myocarditis, who are receiving optimal medical therapy,
and who have reasonable expectation of survival with a good functional status
for more than one year. Data are lacking regarding specific late risks of VT and
sudden cardiac arrest in subjects with myocarditis who present with VT or sudden
cardiac arrest, so this recommendation is based solely upon indirect data on
patients with various types of heart disease (particularly ischemic heart
disease). (See "Secondary prevention of sudden cardiac death in heart failure
and cardiomyopathy".)
●Complete heart block and/or symptomatic bradycardia are indications for pacing
during the acute phase of myocarditis. This conduction abnormality is often
transient; as a result, use of a temporary pacemaker should be the first
step.
Anticoagulation — Indications for anticoagulation in patients with
myocarditis include standard general indications such as evidence of systemic
embolism or presence of acute left ventricular thrombus. Standard criteria for
anticoagulation for atrial fibrillation should be applied; most patients with
atrial fibrillation and HF meet criteria for long-term anticoagulation due to
the significantly increased risk of embolization. In contrast, HF and/or low ejection fraction in patients with sinus rhythm
are not generally accepted as indications for anticoagulation. (See "Secondary
prevention for specific causes of ischemic stroke and transient ischemic attack"
and "The management of atrial fibrillation in patients with heart failure",
section on 'Anticoagulation' and "Atrial fibrillation: Anticoagulant therapy to
prevent embolization" and "Secondary prevention for specific causes of ischemic
stroke and transient ischemic attack", section on 'Cardiogenic embolism' and
"Antithrombotic therapy in patients with heart failure".)
Things to avoid
Nonsteroidal
antiinflammatory drugs — In animal
models of myocarditis, nonsteroidal antiinflammatory drugs are not
effective [50-52].
To the contrary, they may actually enhance the myocarditic process and increase
mortality.
In addition, nonsteroidal antiinflammatory drugs should be avoided in
patients with HF generally, given the risk of HF exacerbation and possible risk
of increase mortality. (See "Drugs that should be avoided or used with caution
in patients with heart failure", section on 'Nonsteroidal antiinflammatory
drugs' and "Nonselective NSAIDs: Adverse cardiovascular effects", section on
'Patients with heart failure'.)
Heavy alcohol
consumption — We suggest alcohol
restriction to at most one alcoholic drink per day (14 to 15 g alcohol), since
heavy alcohol intake may enhance the severity of the myocarditis [53].
However, the optimum threshold for alcohol consumption in this clinical setting
is uncertain (See "Cardiovascular benefits and risks of moderate alcohol
consumption".)
Exercise — Physical activity should be restricted to reduce
the work of the heart during the acute phase of myocarditis, especially when
there is fever, active systemic infection, or HF. The efficacy of this
recommendation has been demonstrated in animal models. Exercise in murine
coxsackievirus infection increased viral replication in the heart and heart
weight compared to controls [54].
The optimum duration of exercise restriction is uncertain. We agree with the
suggestion of the European Society of Cardiology Working Group on Myocardial and
Pericardial Diseases to restrict physical activity of athletes as well as
non-athletes during the acute phase of myocarditis and for at least six months
[35].
This recommendation is based upon expert opinion.
MANAGEMENT OF SPECIFIC
DISORDERS — Limited data are available
to support specific therapies directed at the causes of myocarditis.
Immunosuppressive therapy is suggested for specific autoreactive disorders such
as giant cell myocarditis (GCM), sarcoidosis, noninfectious eosinophilic
myocarditis, and autoreactive myocarditis in the context of known extra-cardiac
autoimmune disease (eg, lupus myocarditis). For lymphocytic myocarditis,
combination immunosuppressive therapy is an option in select patients with
biopsy-proven, virus-negative lymphocytic myocarditis refractory to standard
heart failure (HF) therapy.
In addition, rare non-viral infectious forms can be treated according to
specific etiology (table 1). There are a number of causes (primarily infectious)
of myocarditis for which there is specific therapy, such as Mycoplasma or Lyme
disease (Borrelia burgdorferi) (table 1) [1].
Of note, though specific therapy is available for these causes, it has not been
established that such therapy favorably affects the myocarditic process.
Lymphocytic myocarditis
Overview of therapy for
lymphocytic myocarditis — The efficacy
of antiviral, immunosuppressive, and intravenous immunoglobulin therapies in
patients with lymphocytic myocarditis has not been established. Although data
are limited, combination immunosuppressive therapy is an option in select
patients with biopsy-proven, virus-negative lymphocytic myocarditis refractory
to standard symptomatic HF therapy. (See 'Immunosuppressive therapy' below.)
Antiviral therapy — Although viral infection is the most common
identified cause of lymphocytic myocarditis [1,55],
the efficacy of antiviral therapy for myocarditis is uncertain. Routine
antiviral therapy is not recommended to treat myocarditis.
Antiviral therapy with ribavirin or interferon alfa reduces the severity of
myocardial lesions and mortality in experimental murine myocarditis due to
Coxsackievirus B3 [56-59].
However, this beneficial effect is seen only if therapy is started prior to
inoculation or soon thereafter. The applicability of these findings to humans is
therefore uncertain, since patients with viral myocarditis are usually not seen
in the earlier stages. A case report suggested possible benefit from alpha
interferon in patients with enterovirus-proven myocarditis [60].Preliminary data suggest that antiviral therapy with interferon beta may be beneficial for patients with chronic dilated cardiomyopathy (DCM) and evidence of viral genome in endomyocardial biopsy (EMB) specimens by the polymerase chain reaction (PCR). In the randomized controlled multicenter Beta Interferon for Chronic Cardiomyopathy trial, 143 patients with DCM with evidence of myocarditis and confirmed myocardial viral infection were randomly assigned to interferon beta or placebo; preliminary results were presented in abstract form [61]. Treatment with beta interferon significantly reduced myocardial viral load but virus (particularly parvovirus B19) persisted in some patients [62]. Beta interferon improved patient global assessment compared to placebo at 24 weeks and improved New York Heart Association functional class compared to placebo at 12 weeks but not at 24 weeks [61].
Immunosuppressive
therapy — Preliminary studies suggest
that immunosuppressive therapy may be beneficial in selected patients with
chronic myocarditis but it has not proven to be effective in acute lymphocytic
myocarditis of unspecified etiology. Further study is needed to determine if the
absence of viral genomes on EMB identifies patients who are more likely to
improve with immunosuppressive therapy [23,63].
Because inflammation may persist in the myocardium after clearance of the
initial pathogen, triggered by endogenous autoantigens, it has been postulated
that immunosuppressive therapy might be effective in select cases of
myocarditis, as supported by some experimental work. However, the effect of
immunosuppression varies with the mouse strain, virus, and treatment and timing
of therapy. As an example, mycophenolate mofetil inhibited the development of
Coxsackie B virus myocarditis [64].
Conversely, both glucocorticoids and cyclosporine exacerbate acute murine viral
myocarditis [65,66].
A systematic review including eight randomized controlled trials found that glucocorticoid therapy did not reduce mortality or improve functional status in patients with viral myocarditis, though improvement in left ventricular ejection fraction (LVEF) was suggested [67]. Although some observational, mostly uncontrolled, clinical studies have suggested clinical benefit from combination immunosuppressive therapy with glucocorticoids, azathioprine, or cyclosporine [68-70], evaluation of true effectiveness is difficult in myocarditis because of the high rate of spontaneous recovery [71,72].
No benefit from immunosuppressive therapy was found in acute myocarditis of unspecified etiology. In the randomized, controlled trial Myocarditis Treatment Trial, 111 patients with a histopathologic diagnosis of myocarditis of unspecified etiology and an LVEF of less than 45 percent were randomly assigned to receive conventional therapy alone or immunosuppression with either cyclosporine or azathioprine for 28 weeks [4]. In all patients, the LVEF improved from 25 to 34 percent and the mortality rate was 20 percent at one year and 56 percent at 4.3 years. There was no difference in outcome in the two treatment groups. A more robust inflammatory response was associated with less severe disease and a greater improvement in cardiac function.
In contrast to the lack of benefit seen in acute myocarditis of unspecified etiology, patients with chronic myocardial inflammation may respond to immunomodulatory therapy, as suggested by two randomized controlled trials:
●In a trial of 84 patients with
a DCM of greater than six months duration who had evidence of chronic
inflammation on biopsy, the patients were randomly assigned to receive either
immunosuppression (with glucocorticoid plus azathioprine) or placebo for three
months and then were followed for two years [73].
There was no difference in the primary end point (death, heart transplantation,
or hospital readmission) at two years (23 versus 21 percent for placebo).
However, patients treated with immunosuppressive therapy had a significantly
greater improvement in LVEF and clinical status.
●A randomized trial (the
Tailored Immunosuppression in Inflammatory Cardiomyopthy [TIMIC] study) compared
outcomes with immunosuppressive treatment (glucocorticoid plus azathioprine) as
compared to placebo in a chronic stable DCM population [63].
Of 512 patients with LVEF ≤45 percent who were screened with EMB, 85 subjects
without viral genomes by PCR were assigned to either azathioprine and prednisone
or placebo for six months. The immunohistological criteria were the presence of
>14 CD45 or >2 CD3 positive T cells per high power field. The presence of
circulating anti-heart antibodies was not required for enrollment. The LVEF
improved by >10 percent in 38 of 43 patients treated with immunosuppression,
compared to none of the patients treated with placebo. The placebo-treated
patients' mean LVEF declined from 27.8 percent to 19.7 percent after six months.
Clinical improvement in the immunosuppression treated subjects was reflected in
significantly lower average New York Heart Association functional class (table
2) at six months.
There are several possible explanations for the lack of effect on event-free
survival in the studies of acute cardiomyopathy:
●Most patients with acute
cardiomyopathy improve with standard HF care. As a result, an additive effect of
immunosuppressive treatment is not detectable, because of this improvement in
the control arms.
●Patients in the Myocarditis
Treatment Trial were treated without excluding those with active or chronic
viral myocarditis, in whom immunosuppression is not indicated and may be
detrimental [23,65,66].
Conversely, immunosuppression was beneficial in patients with virus-negative
autoreactive acute and chronic myocarditis with or without positive serum
anti-heart autoantibodies [23,63].
●Immunohistochemical markers of
immune activation may be more sensitive compared with the standard Dallas
criteria to identify a patient population, especially in chronic DCM, in which
there may be benefit to immunosuppression [73,74].
It is possible that further studies may identify a subset of patients with
acute myocarditis responsive to such a regimen [75,76].
A possible relationship between responsiveness to immunosuppressive therapy and presence of cardiac autoantibodies was suggested by an uncontrolled study of 41 patients with progressive HF for six months or more who were unresponsive to standard therapy and who had active lymphocytic myocarditis on biopsy [23]. All 41 were treated with prednisone and azathioprine. The following findings were noted:
●Twenty patients were
nonresponders (no improvement in LVEF), 17 had viral genomes in biopsy
specimens, and none had cardiac autoantibodies.
●Twenty-one patients were
responders (rapid improvement in LVEF from 26 to 47 percent) with evidence of
healed myocarditis on repeat myocardial biopsy; 19 had cardiac autoantibodies
(identified by indirect immunofluorescence) and only three had viral genomes in
biopsy specimens (all hepatitis C virus).
Although it is possible that the presence of cardiac autoantibodies simply
identified patients who had spontaneous improvement, other data cited above
suggested that such patients may have a worse prognosis [14].
Further support for the pathogenicity of autoantibodies, perhaps particularly
those of the IgG3 subclass, comes from clinical improvement following
immunoadsorption against columns that remove these antibodies in patients with
idiopathic DCM [77-80].Limited data are available on the use of immunosuppressive therapy of lymphocytic myocarditis in the setting of unexplained ventricular arrhythmias. In one study, 17 of 65 patients had unexplained ventricular arrhythmias in the apparent absence of structural heart disease [81]. Twelve of these patients underwent EMB and six had evidence of lymphocytic myocarditis. These six patients were treated with prednisone and azathioprine; none had recurrent spontaneous arrhythmias and none had ventricular arrhythmias that could be induced by electrophysiologic stimulation despite cessation of antiarrhythmic medications. Since data are limited, the indications for and value of detection of myocarditis in this setting are controversial. (See "Endomyocardial biopsy", section on 'Unexplained arrhythmias'.)
Intravenous
immunoglobulin
Myocarditis — Intravenous immunoglobulin (IVIG) has antiviral
and immunomodulatory effects, suggesting that it may play a role in the
treatment of viral myocarditis. However, a systematic review concluded that
there are insufficient data from methodologically strong studies to recommend
routine IVIG therapy in patients with acute myocarditis [82].
There are no controlled randomized data on IVIG in pediatric or adult patients
with acute or chronic myocarditis or DCM with biopsy-proven viral or
autoreactive myocardial inflammation.
Dilated
cardiomyopathy — The efficacy of IVIG
in treating DCM is uncertain. As noted above, some patients with DCM have
evidence of myocarditis. Although viral infection is the most commonly
identified cause for myocarditis presenting as DCM, investigation does not
reveal an etiology in approximately 50 percent of patients. The majority of
these cases probably result from an occult infection, an autoimmune process, or
the early stages of a genetically determined myocardial disease. The possible
role of autoimmunity has led to evaluation of the effectiveness of IVIG in
patients with DCM.
As described below, a small randomized trial found no benefit in patients
with acute (recent-onset) DCM [71]
but another trial suggested a benefit in patients with chronic DCM [83].
The randomized controlled IMAC trial of 62 patients with recent-onset (≤6 months of symptoms) DCM with LVEF ≤40 percent found that the improvement in LV function was the same with IVIG (1 g/kg per day for two days) and placebo [71]. Eleven percent of patients had "Dallas criteria" positive myocarditis. At one year, both groups of patients did well as the LVEF rose from 25 percent at baseline to 42 percent. Thirty-six percent had a normal LVEF, and the transplant-free survival at one and two years was 92 and 88 percent. [71].
In contrast, in a randomized, placebo-controlled trial of 40 patients with chronic DCM of unspecified etiology, IVIG significantly improved LVEF, while no improvement in LVEF was seen with placebo [83].
Giant cell myocarditis — Observational data suggest that patients with GCM
treated with certain immunosuppressive regimes have improved survival compared
to patients who do not receive immunosuppressive treatment [29,84].
Among 22 patients treated with immunosuppressive medications that included
cyclosporine, the average transplant-free survival was 13 months compared with
only three months among 30 patients who did not receive therapy [29].
These results were confirmed in a prospective uncontrolled study of 11 patients
with GCM who were treated with one year of cyclosporine and glucocorticoids;
nine patients also received 7 to 10 days of muromonab-CD3 [84].
Among the 11 patients, there was only one death and two transplantations during
one-year follow-up. A benefit from immunosuppressive therapy was also suggested
by a study of 32 patients with GCM, including 26 patients treated with combined
immunosuppression (two to four drugs; including cyclosporine in 20 patients) [30].
Among the 26 patients treated with immunosuppression, the Kaplan–Meier estimate
of transplant-free survival from diagnosis was 77 percent at one year, 63
percent at two years, and 63 percent at five years.
Myocardial inflammation appears mediated by T cells and giant cells. Therapy
directed at T cells may therefore be of benefit, as suggested by case reports of
treatment with muromonab-CD3 [84-86].
Further study is needed to determine the efficacy of this approach.
Eosinophilic
myocarditis — Eosinophilic myocarditis
may occur in association with malignancy, parasite infection, hypersensitivity
myocarditis (HSM), endomyocardial fibrosis, and with the idiopathic
hypereosinophilic syndrome. (See "Etiology and pathogenesis of myocarditis",
section on 'Hypersensitivity myocarditis' and "Approach to the patient with
unexplained eosinophilia" and "Clinical manifestations, pathophysiology, and
diagnosis of the hypereosinophilic syndromes" and "Endomyocardial
fibrosis".)
Treatment of the various types of eosinophilic myocarditis includes high-dose
glucocorticoid therapy and removal of the offending drug (in the case of HSM) or
treatment of the underlying disorder (eg, parasite infection or
hypereosinophilic syndrome) [87].
(See "Treatment of the hypereosinophilic syndromes".)
Cardiac sarcoidosis — Treatment of cardiac sarcoidosis, including the
role of glucocorticoid therapy and implantable cardioverter defibrillator
implantation, is discussed separately. (See "Cardiac sarcoidosis".)
Celiac disease — Improved cardiac function and arrhythmias have
been reported in patients with celiac disease and myocarditis or DCM following a
gluten-free diet with or without immunosuppressive therapy, but controlled data
are lacking [32,33].
(See "Etiology and pathogenesis of myocarditis", section on 'Celiac
disease'.)
Experimental
therapies — A number of experimental
therapies have been evaluated in rodent models of myocarditis, including
verapamil [88],
anti-tumor necrosis factor antibodies [89],
opiate receptor antagonists [90],
and the nasal administration of cardiac myosin, which induces antigen-specific
tolerance and suppresses the autoimmune response to native cardiac myosin
induced by viral infection [91].
The relevance of these therapies to human disease remains to be determined.
The possible beneficial effect of herbal remedies in viral myocarditis was
evaluated in a review [92].
Forty randomized trials including 3448 patients were included; all trials were
conducted and published in China. The methodologic quality of the trials was
generally low. Significant effects on arrhythmia, cardiac enzymes, and/or cardiac function were seen in studies of three
agents. Further study of these agents may be justified [93],
but clinical use cannot be recommended at present.
FOLLOW-UP — As noted above, most patients with acute
myocarditis have partial or full clinical recovery. In some cases, however, the
process may continue subclinically, eventually becoming severe enough to produce
symptoms, often with dilated cardiomyopathy [10-12,16,94,95].
The likelihood of these late complications is increased in patients who present
with greatly diminished left ventricular function.
As a result, all patients with myocarditis should be followed, initially at
intervals of one to three months. Physical activity, especially competitive
sports, should be permitted only gradually, and their tolerance monitored. The
examiner should be alert to persistent or recurring S3 and S4 gallops.
Echocardiography should be used for monitoring the size of the cardiac chambers,
valve function, and the left ventricular ejection fraction. If the
echocardiogram does not provide the necessary information, cardiovascular
magnetic resonance, nuclear testing, or cardiac computed tomography are
alternatives, depending upon availability. We assess cardiac function at one and
six months and then yearly or as indicated by symptoms.
PREVENTION — Vaccination has been effective in preventing some
forms of viral myocarditis but the role for vaccination and other types of
infection control in preventing other types of myocarditis is largely unknown
[96].
As a result of the widespread use of vaccination in developed countries,
myocarditis secondary to measles, rubella, mumps, poliomyelitis, and influenza
is now rare. Similarly, the recognition of trichinellosis by meat inspection has
all but eliminated this infection. It is possible that vaccines against other
cardiotropic viruses may prevent viral myocarditis, as suggested by success with
this approach in murine models [96].
INFORMATION FOR
PATIENTS — UpToDate offers two types of
patient education materials, “The Basics” and “Beyond the Basics.” The Basics
patient education pieces are written in plain language, at the 5th to
6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best
for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the
10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
“patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient
information: Myocarditis (The Basics)")
SUMMARY AND
RECOMMENDATIONS
●The prognosis of myocarditis
varies widely and varies with the underlying cause and the severity of
presenting symptoms. (See 'Variable disease course' above.)
•Patients with lymphocytic
myocarditis may have subclinical disease, slowly progressive disease leading to
dilated cardiomyopathy (DCM), or fulminant disease that may be fatal or may
fully resolve with supportive care. (See 'Spectrum of disease' above.)
•The clinical course for giant
cell myocarditis usually includes acute or fulminant deterioration in left
ventricular systolic function despite standard treatment for heart failure (HF),
frequent ventricular arrhythmias, and heart block. (See 'Giant cell myocarditis'
above.)
•Eosinophilic myocarditis occurs
in a variety of clinical settings, including hypersensitivity myocarditis
(typically with a rapidly progressive course) and hypereosinophilic syndrome
(typically with a more gradual course of biventricular HF). (See 'Eosinophilic
myocarditis' above.)
•Patients with myocarditis or
DCM associated with celiac disease are at risk for progressive HF and
arrhythmias if untreated. (See 'Celiac disease' above.)
●Treatment of myocarditis
includes general measures, including HF therapy and treatment of arrhythmias.
Potential options for patients with refractory HF despite optimum medical
therapy include mechanical circulatory support (eg, ventricular assist devices)
and cardiac transplantation. (See 'General management' above.)
●Immunosuppressive therapy is
suggested for specific autoreactive disorders such as giant cell myocarditis,
sarcoidosis, noninfectious eosinophilic myocarditis, and autoreactive
myocarditis in the context of known extra-cardiac autoimmune disease (eg, lupus
myocarditis). (See 'Management of specific disorders' above.)
●Patients with myocarditis
should avoid nonsteroidal antiinflammatory drugs, heavy alcohol consumption, and
exercise. (See 'Things to avoid' above.)
●All patients with myocarditis
should receive routine follow-up, including serial echocardiography (or other
cardiac imaging). (See 'Follow-up' above.)
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and License Agreement.
REFERENCES
Topic 4935 Version 5.0
• All rights reserved. •
© 2015 UpToDate, Inc.
Disclosures
Disclosures: Leslie T Cooper, Jr, MD Nothing to disclose. William J McKenna, MD Nothing to disclose. Susan B Yeon, MD, JD, FACC Nothing to disclose.
Contributor disclosures are reviewed for
conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced
content is required of all authors and must conform to UpToDate standards of
evidence.
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