His Tests Ruled Out a Heart Attack—But One Doctor Wasn’t Convinced
Unfortunately, a number of challenges stood in the way of diagnosing the young man's rapidly deteriorating condition...
A Medical Mystery
The patient: Nicolaas (name has been changed), 40, a part-time janitor
The symptoms: Worsening shortness of breath
The doctor: Dr. Laura de Graaff, an internist-endocrinologist at Erasmus University Medical Center in the Netherlands
Nicolaas was born with Prader-Willi syndrome, a genetic disorder that affects about one in 10,000 to 30,000 individuals worldwide. People with this disorder often have a mild to moderate intellectual disability. They also have a constant, intense hunger, and many go to great lengths to feed their appetites.
For more than a dozen years, Nicolaas had been living fairly independently in his own apartment, visited by support staff. He worked part time as a janitor. He’d always craved food and had been heavy his whole adult life, but in 2017 he began putting on more pounds. His physical condition deteriorated. Swelling in his legs made it more difficult to walk, and he had trouble catching his breath. He had to quit his job.
Then, over a two-week period, Nicolaas’s shortness of breath suddenly worsened. He began sleeping propped up on pillows because he couldn’t lie flat comfortably.
Nicolaas’s family doctor wasn’t sure what was wrong, but was able to get him an urgent appointment at an outpatient clinic for adults with rare syndromes. The clinic, founded in 2015 by Dr. Laura de Graaff at the Erasmus University Medical Center in Rotterdam, is the only one of its kind in the Netherlands. The waiting list is normally months long.
Difficult to Diagnose
De Graaff was instantly concerned when she met Nicolaas. Although only 40, he had high blood pressure, high cholesterol, asthma and diabetes. He was obese. And he was so short of breath that he couldn’t speak in full sentences without gasping for air.
Shortness of breath has many causes, but most involve the heart or the lungs. Nicolaas could be exhibiting asthma symptoms, or have pneumonia or a blood clot in the lungs. He could also be experiencing a heart attack, or have heart failure. Unfortunately, de Graaff faced a number of challenges in figuring out which it was. For one, says the doctor, Prader-Willi syndrome can interfere with the brain’s ability to regulate body temperature, and can dull pain sensation. Consequently, a fever or discomfort—two common clues for diagnosis—weren’t available. (Here are 20 symptoms you should never ignore.)
Another obstacle was Nicolaas’s obesity. His abdomen was so large that de Graaff couldn’t tell from a physical exam how much excess fluid he’d taken on, or whether his organs were enlarged—both possible indicators of heart failure. Nor could she get a good look at his heart. “When there’s a lot of subcutaneous fat tissue, it can be more difficult for ultrasound waves to get through,” she says.
What de Graaff did have to go on were the sound of wheezing and crackling from Nicolaas’s lungs, and the presence of swelling up to his chest.
De Graaff admitted Nicolaas to the hospital for fast-tracked testing. Blood analysis showed that infection was unlikely, and was negative for substances released during a heart attack. A chest X-ray confirmed no pneumonia. Sometimes swelling builds up when the kidneys aren’t working well, but Nicolaas’s function was normal. So were his liver tests. She tried increasing his asthma medication: “It helped a bit, but not enough.”
After clearing Nicolaas of lung problems, de Graaff felt sure his heart was in trouble. She ran a blood test that checks for NT-proBNP, a peptide released when the heart is overworked and losing its ability to pump effectively. The result was negative. For de Graaff, this was shocking. “I’d trusted my gut feeling. I thought, this cannot be true.”
An MRI would provide a better picture than the ultrasound, but since the negative NT-proBNP ruled out heart failure, she’d never persuade a cardiologist it was necessary. “MRI is expensive, and there aren’t many machines in the building,” de Graaff explains.
Meanwhile, she and her team touched base with Nicolaas several times a day. “We tried to explain everything in simple words.”
Much remains unknown about Prader-Willi syndrome, and de Graaff was determined to dig deeper, searching online medical journals for something to go on. “I just started thinking, what’s different about this patient? Obesity was the most striking difference, so I started there.”
A Small Detail Yields Big Results
A couple hours later, de Graaff hit on something—studies showing that, in 15 per cent of obese individuals with known heart failure, the peptide test gave a false negative. De Graaff was elated. Now she had a convincing case for an MRI, and could proceed. She was also angry, she admits. “Why don’t cardiologists know this?”
The MRI results were alarming, showing obstructed and narrowed coronary arteries. Says de Graaff: “He was really at risk of dying suddenly.”
She continued the intravenous diuretic she’d been giving him to drain fluid, and added a beta blocker. “This slows down the heart rate and opens up the narrowed blood vessels, making it easier for the heart to pump the blood around.” Nicolaas’s swelling went down, and his breathing became easier. After his week-long stay in hospital, he was eager to go home.
Nicolaas isn’t out of the woods yet. De Graaff has recommended he live in a group home where his eating will be supervised, but she’s relieved to report that the outlook is more hopeful for him now. “If I had accepted that this was not a cardiac problem, we would have sent this patient home without a diagnosis!”
Next, read the true story of how a woman’s x-ray revealed the astonishing reason for her lifetime of stomach pain.