Case Study: The Dangerous Habit That Led to Non-Ischemic Cardiomyopathy in a Healthy Man

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

What has caused 6 months of worsening dyspnea leading to respiratory distress in a healthy 54-year-old man who never smoked? Follow the extensive investigative process pursued by Emmanuel U. Emeasoba, MD, of Maimonides Medical Center in Brooklyn, New York, and colleagues to confirm the surprising cause of the patient's symptoms, as described in the American Journal of Case Reports.

Presentation, Examination, and Test Results

The patient presented to the emergency department suffering from increasing shortness of breath, which he said had been ongoing for 6 months, noting that the dyspnea initially occurred only with physical activity, but it had slowly worsened to the point that he became breathless even without exertion.

He added that he was experiencing swelling and pain in his lower legs, but had no chest pain, heart palpitations, dizziness or fainting episodes, fever, nausea, or vomiting. He had never smoked cigarettes nor did he drink alcohol. He had no significant family history of heart disease or sudden cardiac death, and he was not taking any medications.

His one recreational pleasure, he said, was chewing and smoking miraa, also known as khat or qat -- something he had done for 6 hours a day for the past 40 years. He explained that this cultural practice is very common in his native Yemen, where it is used to bond with friends and family.

On physical examination, clinicians noted that the patient was in respiratory distress but alert and well-oriented to time, place, and person. He was not feverish, his respiration rate on 4 liters/min of oxygen through a nasal cannula was 26 breaths per minute; his heart rate was 96 beats per minute, and his blood pressure was 110/70.

Cardiopulmonary examination revealed a bulge in his jugular vein, with bilateral rales on auscultation as well as a grade 2 holosystolic murmur in the mitral and tricuspid areas. Clinicians also noted that both his lower legs had 2+ pitting edema up to the mid-shins.

There were no notable findings from laboratory tests including a complete blood count and a comprehensive metabolic panel, and his thyroid function was also normal. However, his B-type natriuretic peptide level was elevated at 2,103 pg/ml and his HbA1c was 7.6 (4-6%). EKG findings showed that his sinus rhythm was normal with non-specific T-wave inversion in V5-V6 and no acute ischemic changes. Results of a COVID test were negative.

Next Steps

Clinicians ordered a chest x-ray, which showed an enlarged cardiac silhouette with signs of pulmonary venous congestion.

Emeasoba and colleagues followed up with chest CT without contrast, which revealed pleural effusions with interlobular septal thickening in both lungs. Based on the patient's overall clinical profile and the laboratory and imaging findings, the team arrived at a diagnosis of decompensated heart failure.

The patient was admitted to the cardiology telemetry unit for further workup and management, and started on IV furosemide 40 mg. His symptoms responded well to therapy, and he reported feeling much less short of breath and was able to breathe on room air.

Transthoracic echocardiogram (TTE) showed a left ventricular ejection fraction of 16-20% and global cardiomyopathy confirmed a presumed diagnosis of heart failure. The TTE also revealed heart valve regurgitation, which was severe in the mitral valve and moderate in the tricuspid valve. As well, vascular arterial and venous duplex studies of the patient's lower legs showed he was not affected by hemodynamically significant stenosis or venous thrombosis.

Clinicians then set out to determine what had caused the patient's heart failure; telemetry observation during his time in the hospital showed no signs of paroxysmal atrial fibrillation or premature ventricular complexes.

To determine if the cardiomyopathy was due to ischemia, clinicians performed a left heart catheterization, which revealed normal coronary arteries. Ongoing diuresis and optimization of the patient's heart failure medications, including diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors, were associated with clinical improvement. Before discharging the patient, the team placed him on a life vest for primary prevention of fatal cardiac arrhythmias.

A repeat TTE was planned for 3 months after discharge, to reevaluate his ejection fraction and mitral and tricuspid regurgitation as well as to decide if his condition as an outpatient warranted implantation of an automatic implantable cardioverter defibrillator and a possible Mitraclip. (The case report didn't include any further information after that.)

Khat Practices Explained

Emeasoba and co-authors noted that while khat chewing has a well-documented link with ischemic cardiomyopathy, this appears to be the first report of non-ischemic cardiomyopathy in this setting.

The team explained that cardiomyopathy in general is "believed to be due to the increased sympathomimetic activity caused by cathinone, which is the principal pharmacologically active substance in khat, with various effects on the cardiovascular system, including the release of stored norepinephrine, adrenaline-induced renal and coronary vasoconstriction, hypertension, and tachycardia."

The authors noted that in some societies in Yemen and other East African countries, khat is cultivated as a small tree and the fresh leaves are chewed daily for the "aromatic odor and slightly sweet taste." In these places, chewing khat is an acceptable practice and is popular in social gatherings such as weddings and even funerals.

The leaves contain three significant alkaloids -- cathinone, norpseudoephedrine (cathine), and norephedrine – which are released when chewed, Cathinone is a stimulant and the primary source of the desired effects such as excitement, loss of appetite, and euphoria.

Consuming khat has effects on the cardiovascular, neurologic, respiratory, endocrine, and digestive systems, the case authors explained. The substance can cause elevated heart rate and blood pressure, and tachycardia due to "sympathomimetic/vasomotor effects on the myocardium and coronary vessels [which] are mediated via beta-1-adrenoreceptors."

Khat is considered a drug of abuse by the World Health Organization, although the substance is thought to be used by about 20 million people worldwide, the team noted, adding that although it was rarely used in Westernized nations in the past, use is increasing, due in part to growing immigration of khat users, many of whom live in marginalized communities in the Western world.

Cardiovascular effects such as myocardial ischemia, which is most commonly documented, are dose-related, the case authors noted, citing data showing an approximate 39-fold increased heart attack risk in khat users versus non-users. And data from the acute coronary syndrome registry in the Persian Gulf identified khat chewing as an independent risk factor for in-hospital mortality, recurrent ischemia, and heart failure.

Emeasoba and colleagues also cited a study showing that khat chewing independently increased the risk for recurrent ischemia and heart failure, and suggested that "khat chewers had a higher risk of recurrent myocardial ischemia, cardiogenic shock, and ventricular arrhythmia compared with non-khat chewers."

The case authors noted that their patient had no coronary artery disease (CAD) or cardiovascular risk factors, nor any evidence of metabolic or endocrine disorders, aside from the "surprising" elevation in HbA1c to 7.5 mg/dl in a person whose blood glucose level remained below 200 mg/dl during hospitalization. "In the absence of any identifiable CAD, his severe global [cardiomyopathy] was believed to be non-ischemic in origin ... a structural and functional dysfunction of the myocardium in the absence of CAD," the team wrote.

Furthermore, the group postulated that chronic khat ingestion was responsible for the patient's global cardiomyopathy, given that, like amphetamine, cathinone may also result in dilated cardiomyopathy, and that chronic khat chewing has been linked with elevated mean diastolic pressure. Non-ischemic cardiomyopathy resulting from toxins typically improves with the removal of the offending agent, like alcohol, the authors wrote, adding that they had advised their patient to stop using khat.

Conclusion

The group concluded that chronic khat consumption is recognized as a dangerous habit with serious health consequences and although its association with ischemic cardiomyopathy is well documented, this report involves a case of non-ischemic cardiomyopathy with khat use. Although further research is required to substantiate the relationship, the team said, "it is imperative that khat consumption be considered a risk factor" when assessing for cardiomyopathy, especially among people from the Horn of Africa and the Arabian Peninsula.

Read previous installments in this series:

Part 1: Cardiomyopathy: What are the Signs, What are the Symptoms?

Part 2: Diagnosing Cardiomyopathy: History, Examination, and Testing

Part 3: Cardiomyopathy: Epidemiology, Etiology, and Pathophysiology

Part 4: Case Study: Cardiomyopathy From Epinephrine in Anesthesia

Part 5: Cardiomyopathy: Cascade Screening for Families

Part 6: Cardiomyopathy: Outside the Office

Part 7: Deciding on Implantable Cardiac Devices for Cardiomyopathy