Diagnosis is often made by exclusion via cardiac imaging due to overlap of symptom presentation with ACS.

Young age (<35 years) and lack of coronary risk factors raise the suspicion of congenital coronary anomalies or congenital coronary aneurysm. A careful history to exclude cocaine use (supported by tox screen if needed) is mandatory in STEMI patients without significant atherosclerotic risk factors, as is rheumatic history.

Coronary spasm has also been described with patients receiving chemotherapeutic drugs such as 5-fluorouracil and those taking herbal medicines. A careful medical reconciliation should be performed on all chest pain patients and review of “vasospastic potential” performed, and this includes use of estrogen replacement therapy (coronary dissection).

Hypercoagulable/malignancy history should be reviewed, and subtherapeutic INR for patients on Coumadin should be assessed for the possibility of coronary embolism.

Patients may present with fatigue, weakness, fever, myalgias, arthralgia, headache, abdominal pain, hypertension, nosebleeds, palpable purpura, and/or mononeuritis.

Coronary artery imaging (angiography, MRI, CT) that reveals a “stringof-pearls” sign of sequential proximal coronary aneurysms is suggestive of a vasculitic process. A focused rheumatic history should be performed in all patients with this angiographic finding.

Hematology: ESR is increased in 90% of cases, often to very high levels; C-reactive protein (CRP) correlates with disease activity even better than ESR. Normochromic anemia of chronic disease, thrombocytosis, and mild leukocytosis occur in 30-40% of patients; eosinophilia may occur but is not a feature. Leukopenia or thrombocytopenia occurs only during cytotoxic therapy.

Urinalysis: hematuria, proteinuria, and azotemia.

Core laboratory: serum globulins (IgG and IgA) are increased in ≤50% of cases. Serum C3 and C4 complement levels may be increased. Rheumatoid factor may be present in low titer and ANA positive in vasculitis secondary to connective tissue disorders. ANCA determination provides valuable information and is highly specific for the diagnosis of small vessel vasculitides, particularly Wegener granulomatosis.

Imaging studies: arteriogram, MRI, and ultrasound.

Considerations: cANCA (antiproteinase 3; coarse diffuse cytoplasmic pattern) is highly specific (>90%) for active Wegener granulomatosis. Sensitivity is >90% in systemic vasculitic phase, approximately 65% in predominantly granulomatous disease of respiratory tract and approximately 30% during complete remission.

This condition is seen more commonly in children (90% of cases) but it may affect adults as well.

In adults, renal disease is common. The renal picture may vary, with minimal urinary abnormalities occurring for years. Patients may present with palpable purpura without thrombocytopenia or a coagulopathy and acute abdominal pain, or with purpura and joint symptoms.

Histology: renal or skin biopsy supports the diagnosis; it shows focal segmental necrotizing GN that becomes more diffuse and crescentic with IgA and C3 deposition.

Urinalysis: RBCs, casts, and slight protein in 25-50% of patients. The renal picture varies from minimal urinary abnormalities for years to endstage renal disease within months. Gross hematuria and proteinuria are uncommon.

Hematology: coagulation tests are normal.

Core laboratory: Blood urea nitrogen (BUN) and creatinine may be increased.

Histology: diagnosis is confirmed by histologic examination of the coronary artery (same as for polyarteritis nodosa).

Hematology: anemia (approximately 50% of patients). Leukocytosis (20,000-30,000/µL) with shift to the left occurs during the 1st week; lymphocytosis appears thereafter, peaking at the end of the 2nd week, and is a hallmark of this illness. Increased ESR.

CSF findings: increased mononuclear cells with normal protein and sugar.

Urinalysis: increased mononuclear cells; dipstick negative.

Joint fluid findings: increased white blood cell (WBC) count (predominantly PMNs) in patients with arthritis.

Core laboratory: laboratory changes due to AMI. Acute-phase reactants are increased (e.g., CRP, α-1-antitrypsin); these usually return to normal after 6-8 weeks.

Hematology: increased ESR is found in approximately 75% of cases during active disease but is normal in only 50% of cases during remission. WBC count is usually normal.

Core laboratory: serum proteins are abnormal, with increased γ-globulins (mostly composed of IgM). Female patients have a continuous high level of urinary total estrogens (rather than the usual rise during the luteal phase after a low excretion during the follicular phase).

Tuberculosis coronary arteritis occurs mainly in patients with preexisting pericardial or myocardial tuberculosis.

Syphilitic arteritis can involve the first 3-4 mm of the left and right coronary arteries with an obliterative arteritis.

When a nonviral infectious angiitis occurs, it is almost always accompanied by myocarditis with abscesses and pericarditis.

Core lab blood work, cultures, and PCR analysis should be dictated by systemic clues to the underlying infectious process.

Hematology: increased WBC count (often >20,000/µL), with marked shift to the left and toxic changes in neutrophils. DIC may be present.

Core laboratory: azotemia.

Culture: positive blood culture (Staphylococcus aureus is the most frequent organism; others are Klebsiella, Pseudomonas aeruginosa, enterococci, Candida).

Any recent trauma victim in shock, post-MI patients, patients with comorbid conditions predisposed to effusion (neoplasm, chronic inflammatory disease), and patients with chest pain after a viral prodrome.

Typical signs and symptoms of acute pericarditis include chest pain (often pleuritic and worse with inspiration and supine position), pericardial
friction rub (pathognomonic), ECG changes (e.g., ST elevation, PR depression), and pericardial effusion.

Not all patients will manifest all of these features; the presence or absence of an effusion does not exclude the diagnosis.

Echocardiography: Most useful imaging technique for the evaluation of acute pericarditis and is critical for patients if tamponade is suspected. Small pericardial effusions, undetectable by routine examinations, may be detected, providing support for the diagnosis of pericardial disease. Typically >1 cm of effusion is required for safe performance of pericardiocentesis. Doppler-derived flow-velocity measures of mitral and tricuspid flow may assist in diagnosing tamponade, but it is ultimately a clinical diagnosis based on inspiratory decline in systolic arterial pressure exceeding 10 mm Hg (pulsus paradoxus), which can be also seen in chronic obstructive pulmonary disease (COPD) and pulmonary embolism. The absence of any chamber collapse on echocardiography has a high negative predictive value for tamponade (92%), although the positive predictive value is low (58%). Abnormalities of right heart venous return (expiratory diastolic reversal) are more predictive but cannot be obtained in one third of patients.

Electrocardiography: ECG abnormalities may support a diagnosis or suggest alternative diagnoses, such as MI or early repolarization abnormalities. There are several important distinguishing characters of pericarditis ECGs from that of STEMI patients. There is upward concavity of ST elevations (compared with downward for ischemic) that rarely exceeds 5 mm with PR-segment depression (not in aVR) that is not present with repolarization abnormalities. T-wave inversions may persist with tuberculous, uremic, or neoplastic pericarditis. Electrical alternans suggests large effusion.

Chest x-ray: Generally normal but may detect specific abnormalities, like increased cardiac silhouette with effusions (water-bottle heart), pleural effusion, or evidence of underlying etiology (TB, fungal disease, pneumonia, neoplasm).

Chest CT and MRI detect effusions with high sensitivity and specificity and may provide useful information pertinent to performing pericardiocentesis (hematocrit of effusion, loculations, pericardial thickening). Often, concern of tamponade makes echocardiography the imaging modality of choice for clinically tenuous patients due to its mobility.

Tuberculin skin test or interferon-gamma release assay: Evaluation to rule out TB is recommended for all patients. Additional diagnostic testing for TB, like AFB cultures, should be performed on patients at increased risk on the basis of epidemiologic and clinical factors.