Fontan Surgery for Heart Defects May Not Be Advisable for CMT1A Patients, Case Study Finds

Patients with Charcot-Marie-Tooth disease (CMT) who undergo Fontan surgery to correct a heart defect in childhood may later develop difficulties with the diaphragm — the muscle that allows us to breath — that can cause the earlier heart surgery to fail while leaving them ineligible for a heart transplant, a case study of a CMT1A patient reports.

Its researchers stress the importance of identifying CMT in patients recommended for Fontan surgery, as some disease types — like CMT1A — can result in damage to the nerve controlling breathing and make the procedure fail later in life.

The report, “Fontan Failure Secondary to Charcot-Marie-Tooth–Induced Phrenic Neuropathy,” appeared in the journal Texas Heart Institute Journal.

The study describes a 25-year-old woman experiencing persistent pleural effusions — accumulation of excess fluid between the membranes lining the lungs and chest cavity (pleura) — and abdominal ascites — abnormal fluid buildup in the abdominal cavity.

After being recommended for a heart transplant, she sought a second medical opinion at the Mayo Clinic in Rochester, Minnesota, with the doctors who authored this case study.

She was born with a severe heart defect (one of the heart valves was not working), and at age 2 underwent Fontan surgery, a procedure in which veins carrying blood from the body to the heart are modified to bypass the heart and connect to the main pulmonary artery, that takes blood from the heart to the lungs.

The patient had a family history of CMT, and she genetically confirmed to have CMT1A at age 14. At that time, she had no symptoms of the disease.

At age 19, the patient started to develop pleural effusions, which became persistent when she was 25 and came to the clinic.

Among other symptoms, she was short of breath when she lying flat (orthopnea) or when exercising (exertional dyspnea). A chest radiography and a sniff test showed reduced lung volumes and limited diaphragm movements. (The diaphragm is a muscle that lies beneath the lungs and the heart, and is essential for breathing. When it contracts, chest volume increases and air is drawn into the lungs.)

An ultrasound-guided diaphragmatic electromyogram, an exam that records the electrical activity of the diaphragm aided by ultrasounds, indicated problems in the phrenic nerve, which innervates the diaphragm and controls its movements.

These alterations were consistent with a loss of myelin — the insulating layer around the nerves that is necessary for nerve-to-nerve communication; demyelination is a hallmark of CMT1A and other disease types. Myelin loss at the phrenic nerve would partly paralyze this nerve, weakening the diaphragm’s movement and constraining breathing.

In turn, this loss increased the resistance in the pulmonary arteries  — which conduct the blood from the heart to the lungs — raising pressure at places affected by the Fontan surgery and reducing blood flow from the heart. The woman was also obese and had a spinal deformity that further exacerbated these problems.

Her diaphragm’s limited movement was attributed to the CMT-associated neuropathy, and she was not considered a good candidate for a heart transplant. The woman left the Mayo Clinic for further treatment with her initial medical team. 

This is the first report of progressive phrenic nerve paralysis caused by CMT1A in a patient who had undergone Fontan surgery, the researchers said.

It highlights how CMT-caused “perturbations in basic respiratory mechanics can cumulatively affect Fontan circulation,” they added.

“Our patient’s case calls attention to the adverse effects of advanced CMT1A-induced phrenic neuropathy and secondary diaphragmatic dysfunction; her progressive, incurable respiratory dysfunction not only caused failure of an established Fontan circulation, but also made her ineligible for cardiac transplantation,” the study notes.

CMT types that result in phrenic nerve neuropathy “may be considered a relative contraindication to the Fontan operation” during early childhood, the team added, while acknowledging that an early CMT diagnosis can be difficult in cases where no family history, and disease signs or symptoms, exist.  

While CMT patients whose diaphragm becomes partly paralyzed may benefit from positive-pressure ventilation, they also noted this approach is not suited to those who have had a Fontan intervention, because the ventilation will affect blood flow to the lungs.