Dyspnea, Syncope, and Fatigue in a Middle-Age Patient

What is the cause of this middle-age patient’s dyspnea, syncope, and fatigue? That’s the question addressed by Yi Zhang, PhD, of Hunan Provincial People’s Hospital and Hunan Normal University in China, and colleagues.

As they reported in JAMA Internal Medicine, a patient in their 50s presented to the emergency department with dyspnea, heart palpitations, fatigue, and syncope over the past 4 days. The patient described having symptoms of an upper respiratory tract infection and a fever about 10 days previously. There was no history of cardiovascular disease.

Upon physical examination, the patient’s blood pressure was 98/65 mm Hg, heart rate was 65 beats per minute, and body temperature was 36.6 °C. Lab tests revealed a serum troponin I level of 12.8 ng/mL (normal range <0.10 ng/mL) and a N-terminal pro-B-type natriuretic peptide level of 13,800 pg/mL (normal range <300 pg/mL).

A transthoracic echocardiogram revealed that the patient’s left ventricular ejection fraction was 34%, with decreased range of motion notable in the interventricular septum and left anterior and right ventricular walls. An angiogram showed no evidence of coronary stenosis.

Upon admission to hospital, the patient’s blood pressure dropped to 60/40 mm Hg. The initial ECG showed a wide QRS complex tachycardia. The following day, complete atrioventricular block developed, which required temporary pacing. Upon his return to the ward, clinicians ordered an ECG.

Findings of the initial ECG included regular alternating upward and downward morphologies of QRS complex tachycardia, with ST-segment elevation in leads aVR, III, and V₁ through V₃, and ST-segment depression in the rest of the leads.

“The QRS wave onset was coarse and blunt with ventricular initial (v_i) and terminal (v_t) conduction velocity ratio (v_i/v_t) of less than 1. The QRS axis shifts 180° from left to right with each alternate beat in the same limb lead, suggesting 2 distinct foci of discharge,” Zhang and team wrote.

Based on these findings, the patient was diagnosed with bidirectional ventricular tachycardia (BVT). The next ECG revealed that every QRS wave was preceded by a pacing stimulus, although clinicians noted a delay before the onset of the QRS complex. There was a latency in ventricular capture of 60 and 126 milliseconds in the different ECG leads. Clinicians noted that the extended interval between the pacemaker stimulation spike and initiation of ventricular depolarization supported the diagnosis of first-degree ventricular pacemaker exit block.

A coronary angiogram returned normal results. In light of the observed hemodynamic instability, clinicians used an intra-aortic balloon pump and extracorporeal membrane oxygenation to treat the patient, and later removed the temporary pacemaker. The history of fever, elevated troponin level, BVT, ventricular wall hypokinesia, and cardiogenic shock all supported a diagnosis of fulminant myocarditis. Despite clinicians’ best efforts, the patient died 15 days after mechanical circulatory support was initiated.

Discussion

Ventricular arrhythmias occur frequently in the setting of fulminant myocarditis, Zhang and colleagues noted, and are an important cause of sudden cardiac death. As the most severe form of myocarditis, fulminant myocarditis can result in cardiogenic shock, ventricular tachyarrhythmias, or bradyarrhythmias, and other outcomes include sinus arrest and sinoatrial and atrioventricular blocks, as well as multi-organ failure due to sudden and severe inflammation of the myocardium.

On physical examination, patients with fulminant myocarditis may have signs of heart failure, including decreased blood pressure, accelerated heartbeat, and markedly decreased heart sounds, usually with gallop rhythm, with or without tachypnea. Routine blood tests may reveal elevated neutrophils or lymphocytes, indicating the presence of infection, according to one comprehensive review, which noted that endomyocardial biopsy samples demonstrate numerous infiltrating immune cells in the necrotic myocardium.

According to most reports, the majority of infiltrated cells are T lymphocytes, such as CD3+/CD4+ Treg lymphocytes, CD3+/CD8+ cytotoxic T lymphocytes, and macrophages, while B lymphocytes are seen only rarely.

The current case was unusual in showing none of the ECG signs typical of fulminant myocarditis, such as slow QRS voltage and abnormal Q waves. “Instead, ventricular arrhythmias, including ventricular premature beats, ventricular tachycardia, BVT, and ventricular fibrillation, as well as atrioventricular block, were observed,” the authors wrote.

The case was even more unusual for the ventricular pacemaker exit block that developed after a temporary pacemaker was implanted, they added, describing differential diagnoses of BVT, including digoxin toxicity, aconite poisoning, myocardial ischemia, catecholaminergic polymorphic ventricular tachycardia, and Andersen-Tawil syndrome.

Of infectious etiologies, viral infections such as those due to coxsackievirus B3 and parvovirus B19, adenoviruses, herpes viruses, HIV, and influenza A, are the most common cause of fulminant myocarditis. However, the condition can also occur in the presence of infections caused by bacteria, spirochetes, and parasites, Zhang and colleagues noted.

In considering other possible causes of BVT, the authors eliminated ingestion of digitalis or aconite, which their patient had not been exposed to. Catecholaminergic polymorphic ventricular tachycardia was unlikely since the episodes of BVT occurred in the absence of either exertion or notable emotional stress.

According to the authors, BVT is thought to occur as a result of delayed depolarization “caused by an increased intracellular Ca²⁺ at 2 distinct ventricular foci, a ping-pong mechanism.” Elevation of intracellular Ca²⁺ may be triggered by “spontaneous release from the sarcoplasmic reticulum or increased ryanodine receptor sensitivity.”

As for the mechanism of action in fulminant myocarditis, the group explained that “inflammation activates the ryanodine receptor and results in the release of Ca²⁺ from the sarcoplasmic reticulum, which causes intracellular Ca²⁺ overload, leading to transient inward current, activation of inward sodium current, and subsequent triggered action potential.”

“Lesions of the His-Purkinje conduction system and ventricular myocarditis in FM can both lead to triggered activity, automaticity, and reentry,” they wrote.

This patient’s complete atrioventricular block was managed through implantation of a temporary pacemaker. Blocks of the myocardial conduction system may occur due to temporary inflammatory cell infiltration of the myocardium and excess accumulation of fluid in the myocardial cells and intermyocardial cellular spaces, Zhang and team noted, adding that “ventricular pacemaker exit block is defined as a delay of more than 40 milliseconds or interruption in the transmission of electrical impulses from the pacemaker lead to the ventricle tissue.”

This rare abnormality on ECG tends to be observed in very ill patients with temporary or permanent pacemakers, they said, but also occurs in those with elevated levels of potassium, severe heart disease, heart attack, anti-arrhythmic drug toxicity, or variant (Prinzmetal) angina.

Fulminant myocarditis is a rare cause of ventricular pacemaker exit block, the authors pointed out, but the diagnosis was considered given the patient’s normal serum potassium level. In this case, edema of the myocardial cells and intermyocardial cellular spaces was the probable cause of ventricular pacemaker exit block, they said.

“Although ventricular latency is the commonly recognized feature, more progressive forms of block may occur immediately prior to death,” they wrote, adding that use of extracorporeal membrane oxygenation and removal of the temporary pacemaker may have prevented this patient’s exit block from worsening.

“These rare cardiac phenomena in the clinic are like hidden devils that need to be detected in time to ensure timely correction of reversible factors,” they concluded.