Systemic capillary leak syndrome presenting with fulminant recurrent cardiogenic shock

A 32 year old male, employee at a local brewery, with a history of hypertension presents to the emergency department with cough, myalgia, progressive shortness of breath and substernal chest pain. At the emergency department, the patient was noted to have sinus tachycardia at 110–120 beats per minute, blood pressure of 85–100/55–75 mmHg and otherwise normal vital signs. Initial evaluation revealed leukocytosis at 18,000 cells/mm³, erythrocytosis with hemoglobin 20.5 g/dL, elevated troponin T at 0.12 ng/mL, elevated whole blood lactate at 3.9 mmol/L and pro Brain Natriuretic Peptide (proBNP) at 1,419 pg/mL. A bedside echocardiogram showed normal left and right ventricular function, mild left ventricular hypertrophy and a moderate size pericardial effusion. The patient received 3 liters intravenous normal saline with no improvement in blood pressure which prompted his transfer to a tertiary care facility.

During the patient’s transfer to our hospital, his condition deteriorated with worsening hypoxia and hypotension. On arrival to our coronary care unit, he was immediately intubated for hypoxemic respiratory failure. An arterial line was placed that revealed blood pressure 80–95/65–80 mmHg with no pulsus paradoxus. A repeat echocardiogram revealed severe global left ventricular systolic dysfunction without left ventricular dilatation, thickened left and right ventricular walls, and a moderate size pericardial effusion with no signs of tamponade. Mitral inflow doppler interrogation was not consistent with restrictive physiology. Over concern for cardiogenic shock from fulminant myocarditis, inotropic support with dobutamine was initiated. Right heart catheterization was performed and revealed right atrial pressure of 13 mmHg, pulmonary artery pressure 23/18 mmHg, pulmonary capillary wedge pressure (PCWP) of 18 mmHg and cardiac index of 1.04 L/min/m².

Given signs of hemodynamic decompensation despite inotropic support, the decision was made to initiate veno-arterial extracorporeal membrane oxygenation (VA-ECMO) via femoral vessels. A percutaneous LVAD was implanted to promote unloading and help with recovery of LV function while the patient’s circulation was supported by VA-ECMO¹. Coronary angiography at the time of VAD implantation revealed no significant coronary disease. Endomyocardial biopsy showed a lack of significant immune cell infiltration and some degree of cardiomyocyte vacuolization (Figure 1A), a non-specific finding that has been associated with increased catecholamine levels² and endothelial dysfunction in response to ischemic injury³. Thyroid function studies were normal, whole blood cobalt levels were undetectable, an expanded urine toxicology was unremarkable. An extended viral panel (including HSV 1 and 2, CMV, EBV, Coxsackie A and B, Parainfluenza, Adenovirus, Hepatitis A, B and C and HIV) was negative. A cardiac MRI showed no late gadolinium enhancement.

Figure 1.

A. Endomyocardial biopsy pathology showing cardiomyocyte vacuolization. B. Electric cell-substrate impedance censing results. Human aortic endothelial cells were cultured in separate sterile wells and exposed to the patient’s acute phase serum, serum from a healthy human volunteer, fetal bovine serum and thrombin. Impedance was measured as a function of time after exposure. Cells exposed to the patient’s serum demonstrated a statistically significant decrease in impedance compared to the other subgroups (p<0.0001), consistent with loss of endothelial cell barrier function and increased permeability. Additionally, cells exposed to the patient’s serum showed a longer time to cell barrier recovery compared to the other subgroups (p<0.0001).

Within a week, the patient’s myocardial function improved and mechanical circulatory support was weaned successfully. The patient fully recovered and was discharged from the hospital two weeks after his initial presentation with a presumed diagnosis of atypical stress cardiomyopathy. During the next year the patient had no health-related incidents. Repeat echocardiogram during regular follow up was normal. His leukocytosis and erythrocytosis resolved.

A year after his original hospital admission, the patient presented in the emergency department with shortness of breath preceded by laboratory confirmed Influenza A infection. His initial presentation was notable for marked hemoconcentration (hemoglobin of 22.1 g/dL). His echocardiogram revealed diffuse left and right ventricular hypokinesis along with a small size pericardial effusion and mild left ventricular hypertrophy (LVH). His condition rapidly deteriorated with progressive cardiogenic shock requiring mechanical circulatory support with VA-ECMO. Repeat endomyocardial biopsy did not reveal any evidence of inflammation.

The patient’s recurrent presentation with shock and profound hemoconcentration prompted evaluation for Systemic Capillary Leak Syndrome⁴, a rare disorder whose hallmark are episodic attacks of hemoconcentration and hypovolemia from acute fluid shifts into skeletal muscle; but that has also been reported as an unusual cause of fulminant cardiogenic shock⁵. The diagnosis was confirmed with an elevated VEGF level and a 0.34 g/dL monoclonal spike in the gamma region on serum protein electrophoresis³ which is often present in patients with the disease⁴. Additional confirmation of the disease pathophysiology followed with cardiac MRI that revealed diffuse myocardial edema and with a subsequent experimental assay where human aortic endothelial cells were exposed to a sample of the patient’s acute phase serum and showed a loss of endothelial cell barrier function, increased permeability and longer time to cell barrier recovery compared to cells treated with control human serum^6,7 (Figure 1B). The patient was started on monthly intravenous immunoglobulin (IVIG) therapy for SCLS.

He recovered fully from his second hospital admission and was discharged home. His erythrocytosis resolved and left ventricular size and function normalized. Movies I and II show the transient LVH that was present in the acute phase and resolved in recovery. He has had no further episodes in over one year follow up. In summary, our report highlights an atypical case of SCLS presenting with primary myocardial involvement. Therefore, SCLS should be in the differential diagnosis of patients presenting with otherwise unexplained fulminant cardiogenic shock.