Myocarditis and pericarditis (the ACS mimic and the positional chest pain)

Myocarditis and pericarditis are the inflammations of the heart muscle and the pericardium, most commonly from a viral infection, and they share a clinical space with the acute coronary syndrome — the chest pain, the ECG changes and the troponin rise that can mimic an infarct exactly. The Fellowship candidate must distinguish the pericarditis (the positional, the pleuritic pain, the diffuse ECG changes, the NSAID-responsive course) from the myocarditis (the ACS-mimic, the arrhythmia, the heart failure, the fulminant shock), because the management and the prognosis are very different.[1][2]

Definition and classification

Pericarditis is the inflammation of the pericardium, usually from a viral infection (the coxsackie, the echovirus, the adenovirus, the influenza, the SARS-CoV-2), but also from the bacterial infection, the autoimmune disease (the systemic lupus, the rheumatoid, the vasculitis), the uraemia, the malignancy, the radiation, the post-MI (the Dressler syndrome) and the post-pericardiotomy. Myocarditis is the inflammation of the myocardium, most commonly viral (the same spectrum), but also from the autoimmune disease, the drug (the anthracycline, the clozapine), the heavy metal, the radiation and the post-vaccine (the rare mRNA COVID-vaccine myocarditis in the young male). The two conditions often co-exist — the myopericarditis — because the pericardium and the epicardial myocardium are anatomically contiguous. [1]

Pathophysiology — why the troponin rises and the ECG changes

The pericardial inflammation produces an exudate (the pericardial effusion) and the characteristic ECG changes — the diffuse ST elevation (from the epicardial injury, unlike the focal ST elevation of the STEMI) and the PR depression (from the atrial involvement). The troponin rises when the inflammation extends into the myocardium (the myopericarditis), which is common. The myocarditis in isolation produces a myocyte injury that raises the troponin and may produce a regional wall motion abnormality on the echo (mimicking a STEMI), a heart failure or an arrhythmia. The fulminant myocarditis — a massive, rapidly progressive inflammation of the myocardium — produces a cardiogenic shock within days of a viral prodrome and may need a mechanical circulatory support or an extracorporeal membrane oxygenation as a bridge to recovery. [1]

Differential diagnosis — the ACS mimic and the chest pain

The differential of the pericarditis and the myocarditis is the acute coronary syndrome, and the distinction is the emergency department's task. [1]

Investigations — the ECG, the troponin and the echo

The ECG of the pericarditis shows the diffuse, concave ST elevation in multiple leads (not the focal, convex elevation of the STEMI), the PR depression (in the limb and the precordial leads), and, later, the T-wave inversion. The ECG of the myocarditis may be non-specific, may mimic the STEMI (the regional ST elevation), or may show an arrhythmia (the ventricular ectopics, the VT, the heart block). The troponin is raised in both (higher and more dynamic in the myocarditis; mildly raised in the pure pericarditis). The CRP and the ESR are raised (the inflammatory markers). The echocardiography shows a pericardial effusion (in the pericarditis) and a regional or a global wall motion abnormality (in the myocarditis) with a reduced ejection fraction in the severe case. The cardiac MRI is the gold standard for the myocarditis — it shows the late gadolinium enhancement in the mid-wall (not the subendocardial pattern of the infarct), the T1 and the T2 mapping (the oedema), and the biventricular function. The coronary angiography is the definitive test when the ACS cannot be excluded — the normal coronaries with the elevated troponin and the wall motion abnormality confirm the myocarditis. [1]

Immediate management — the pericarditis and the myocarditis

The management differs by the condition, and the distinction from the ACS is the prerequisite. [1]

Complications and pitfalls

The complications of the pericarditis are the recurrence (30 per cent after the first episode — the colchicine halves it), the constrictive pericarditis (a late, chronic constriction from the organised pericardial thickening — needs the pericardiectomy), and the tamponade (from a large effusion — the serial echo monitors for it). The complications of the myocarditis are the heart failure (the dilated cardiomyopathy), the arrhythmia (the atrial and the ventricular, the heart block, the sudden cardiac death), and the fulminant course (the cardiogenic shock needing the mechanical support). The pitfalls are: giving the NSAIDs to the myocarditis (they may worsen the injury); giving the corticosteroids to the first-episode pericarditis (they increase the recurrence); not monitoring the effusion for the tamponade; not restricting the sport after the myocarditis; and missing the fulminant myocarditis behind a "viral illness with a chest pain." [1]

Prognosis and disposition

The pericarditis is a benign, self-limiting condition in most cases — the symptoms resolve over days to weeks with the NSAID and the colchicine, and the prognosis is excellent (apart from the recurrence). The myocarditis has a variable prognosis — the mild case recovers fully, the severe case may leave a residual cardiomyopathy, and the fulminant case has a mortality of up to 20 per cent but may recover completely with the mechanical support. The patient is admitted for the pericarditis if a large effusion or a high-risk feature is present; the myocarditis is admitted for the troponin rise, the arrhythmia, the heart failure, or the diagnostic uncertainty (the ACS exclusion). The follow-up includes the serial echo, the ECG, the troponin, and the sport-medicine assessment before the return to the exercise. [1]

Aetiology of myocarditis — the viral, the autoimmune and the drug

The myocarditis is the inflammation of the myocardium with the necrosis and the degeneration of the myocyte, and the aetiology is best held in four buckets — the infectious, the immune-mediated, the toxin and the drug, and the systemic.[4][11] The infectious causes dominate: the viruses are the commonest in the developed world (the coxsackie B, the parvovirus B19, the adenovirus, the echovirus, the influenza, the Epstein–Barr, the cytomegalovirus, the HIV, the SARS-CoV-2), followed by the bacterial (the staphylococcus, the streptococcus, the Borrelia of the Lyme disease, the Mycoplasma), the protozoal (the Trypanosoma cruzi — the Chagas disease, the commonest cause of the myocarditis worldwide), the rickettsial, and the fungal. The immune-mediated causes are the giant-cell myocarditis (a rare, rapidly fatal autoimmune disease of the young adult — a medical emergency), the sarcoid, the eosinophilic (the Churg–Strauss, the drug-hypersensitivity), and the collagen-vascular (the systemic lupus, the rheumatoid). The toxin and the drug causes are the anthracycline (the doxorubicin — the dose-dependent cumulative cardiotoxicity), the clozapine, the trastuzumab, the alcohol, the cocaine, the heavy metals, the snake and the scorpion venom, and the immune-checkpoint inhibitors (the anti-PD-1/PD-L1 — an increasingly recognised cause). The systemic causes include the peri-partum cardiomyopathy and the severe sepsis.

Aetiology of pericarditis — the spectrum

The pericarditis is most often idiopathic or viral (together over 80 per cent of the cases in the developed world — the same viral spectrum as the myocarditis, with the coxsackie, the echovirus, the adenovirus, the influenza, and the SARS-CoV-2).[3] The non-viral causes are best remembered by the system: metabolic (the uraemia of the renal failure, the hypothyroid and the myxoedema), autoimmune (the systemic lupus, the rheumatoid, the Dressler syndrome — 2 to 10 weeks after the MI; the post-cardiotomy syndrome), neoplastic (the lung, the breast, the melanoma; the mesothelioma), infectious (the tuberculosis — the commonest cause worldwide; the purulent bacterial from the contiguous pneumonia or the empyema), radiation, and the drug-induced (the procainamide, the hydralazine, the isoniazid — the drug-induced lupus). The tuberculous pericarditis is a high-yield aetiology — suspect it in the endemic area, the HIV-positive patient, or the chronic effusion with the fever and the weight loss, and treat with the anti-tuberculous therapy plus the adjunctive corticosteroid (it reduces the progression to the constriction).

The four ECG stages of acute pericarditis

The ECG of the acute pericarditis evolves through four stages over days to weeks, and recognising the stage is a classic Fellowship question. [1]

The cardiac MRI — the Lake Louise criteria

The cardiac magnetic resonance is the non-invasive gold standard for the myocarditis, and the diagnosis rests on the Lake Louise criteria (updated in 2018).[5][6] The diagnosis requires at least TWO of the three classical criteria — combined, the sensitivity is about 67 per cent and the specificity about 91 per cent, rising further with the parametric T1 and T2 mapping in the 2018 update:

The endomyocardial biopsy and the Dallas criteria

The endomyocardial biopsy is the historical gold standard for the myocarditis, but it is invasive, the inter-observer variability is high, and the sensitivity is low (under 50 per cent because of the patchy disease — the sampling error).[4][11] The Dallas criteria (1987) classify the biopsy as the active myocarditis (the inflammatory infiltrate with the myocyte necrosis), the borderline myocarditis (the inflammatory infiltrate without the myocyte necrosis), or the no myocarditis.[12] The biopsy is now reserved for the clinically suspected fulminant or giant-cell myocarditis (where the histology changes the management — the immunosuppression or the transplant), the refractory cardiogenic shock of the unclear cause, and the suspected cardiac sarcoid or the infiltrative disease. For the routine case, the cardiac MRI has replaced the biopsy.

Fulminant myocarditis — recognition and the resuscitation

The fulminant myocarditis is the distinct, severe phenotype — a sudden, diffuse myocardial inflammation presenting as the cardiogenic shock within hours to days of a viral prodrome — that the emergency physician must not miss behind a flu with the chest pain and the breathlessness.[7][10] The McCarthy cohort established the paradox: the fulminant myocarditis has a HIGHER in-hospital mortality than the non-fulminant acute myocarditis, but a BETTER long-term survival in the survivors (the recovery of the ventricular function is near-complete in those who survive the acute episode).[10]

Drug-induced myocarditis — the high-yield agents

Recurrent pericarditis — the colchicine, the steroid and the anakinra

The recurrent pericarditis — the symptomatic recurrence after a symptom-free interval of at least 4 to 6 weeks — affects about 30 per cent after the first episode, and the recurrence rate climbs with each subsequent episode.[3] The colchicine is the evidence-based prevention: the ICAP trial (the New England Journal 2013) showed that the colchicine 0.5 mg twice daily for 3 months halved the recurrence at 18 months (from 37 to 16 per cent).[9] The management of the recurrence is the same as the first episode (the NSAID plus the colchicine); the corticosteroid is reserved for the failure of the NSAID or the autoimmune cause (it INCREASES the recurrence when used in the first episode). The refractory recurrent pericarditis responds to the anakinra (the recombinant IL-1 receptor antagonist) — an emerging and effective therapy — and the pericardiectomy is the last resort.

Constrictive pericarditis vs restrictive cardiomyopathy

Both present with the right heart failure (the elevated JVP, the hepatomegaly, the ascites, the peripheral oedema) and are notoriously hard to distinguish — the distinction is high-yield because the constriction is curable (the pericardiectomy) and the restriction is not. [1]

The trial evidence — the landmark studies

The disposition — who is admitted and who is discharged

The disposition follows the risk stratification, not the diagnosis. Admit the pericarditis with ANY of: a fever over 38 °C, a subacute onset (over a week), a large pericardial effusion (over 2 cm in diastole), a tamponade physiology, an immunosuppression, an oral anticoagulation, a trauma, a myopericarditis (the troponin raised), or the failure of the first-line therapy. The low-risk pericarditis (the classic viral presentation, a small or no effusion, a negative troponin) may be discharged on the NSAID plus the colchicine with the 24 to 48 hour review and the warning about the red flags. Admit ALL the myocarditis — the troponin rise, the arrhythmia, the heart failure, and the diagnostic uncertainty (the ACS exclusion) all warrant the admission and the monitoring. The fulminant myocarditis goes to the ICU or the HDU and the tertiary centre. [1]

High-yield one-liners — the aetiology and the diagnosis

• The pericardial rub is a triphasic (the systolic, the diastolic, the pre-systolic) scratch best heard at the left sternal border with the patient leaning forward in full expiration — its presence does not exclude a large effusion, and its absence does not exclude the pericarditis.
• The PR depression is the single best ECG discriminator of the pericarditis from the STEMI — and it may be the ONLY early ECG sign.
• The troponin is raised in BOTH the pericarditis and the myocarditis (the myopericarditis) — a raised troponin does NOT distinguish them, and does NOT, by itself, mandate the angiography if the ECG and the echo are typical for the pericarditis.
• The NSAIDs are AVOIDED in the acute myocarditis (they impair the healing, they increase the viral replication in the animal models, and they worsen the myocyte injury) — give the heart-failure therapy and the rest, NOT the ibuprofen.
• The corticosteroids INCREASE the recurrence of the pericarditis when given for the first episode — reserve them for the autoimmune cause, the uraemia, the failure of the NSAID, or the contraindication to the NSAID.
• The colchicine is the ONLY drug proven to reduce the recurrence (the ICAP and the COPE trials) — give it for 3 months.
• The Dressler syndrome is the pericarditis 2 to 10 weeks post-MI — the immune-mediated; treat with the aspirin (avoid the NSAID in the first week post-MI).
• The giant-cell myocarditis is the young adult with the rapidly progressive heart failure and the VT — the biopsy (the giant cells), the immunosuppression, and the transplant.
• The cardiac MRI Lake Louise criteria — TWO of the three: the T2 oedema, the early gadolinium, the late gadolinium (the mid-wall or the subepicardial, NOT the subendocardial).
• The fulminant myocarditis — support with the MCS (the VA-ECMO) as the bridge to recovery; the survivors recover the ventricular function.
• The recurrent pericarditis — the anakinra (the IL-1 receptor antagonist) for the refractory case. [1]

The bedside red flags — the clinical triggers

Special populations

The athlete with the myocarditis is at a high risk of the sudden cardiac death — the return to the sport is restricted for 3 to 6 months, and the clearance requires a normal echo, a normal ECG, a normal exercise test, and no biomarker evidence of the ongoing inflammation. The post-COVID-vaccine myocarditis (the rare mRNA-vaccine-associated myocarditis in the young male, typically within a week of the second dose) is usually mild and self-limiting. The pregnant patient with the pericarditis is managed with the aspirin (the ibuprofen is avoided in the third trimester — the premature closure of the ductus). The anticoagulated patient is managed with caution (the NSAID increases the bleeding risk). [1]

Evidence and regional guidelines

The contemporary framework is the ESC 2015 pericardial-disease guideline (the NSAID + colchicine for the pericarditis)[2] and the contemporary myocarditis literature (the MRI diagnosis, the sport restriction, the mechanical support for the fulminant).[1] The drug choices and the sport-restriction criteria follow the local cardiology and the sports-medicine protocol.

SAQs

Exam pearls

• Pericarditis: positional, pleuritic pain + diffuse ST elevation + PR depression → NSAID + colchicine 0.5 mg bid for 3 months.
• Myocarditis: ACS mimic (the troponin, the ECG, the wall motion) in a young patient with a viral prodrome → supportive + sport restriction 3-6 months.
• The troponin is raised in BOTH (the myopericarditis) — it does not distinguish them.
• The coronary angiography (the normal coronaries) excludes the ACS and confirms the myocarditis in the unclear case.
• The colchicine halves the recurrence rate (from 30 to 15 per cent).
• The fulminant myocarditis → mechanical circulatory support (Impella/VA-ECMO).
• NSAIDs are AVOIDED in the myocarditis (they worsen the myocyte injury); corticosteroids are avoided in the first-episode pericarditis. [1]

Red flags