Refractory Coronary Vasospasm And Sudden Cardiac Death In A Young Woman With Desmoplakin Mutation

Abstract

Listen

Translate article

Therapy is limited for refractory coronary vasospasm leading to ventricular arrhythmia and sudden death. Mutations in Desmoplakin (DSP) have been described as a distinct form of arrhythmogenic cardiomyopathy characterized by chest pain and ventricular arrhythmia. Case: A healthy 31-year-old white female presented at 24 weeks gestation with flank pain and substernal chest pain. She was treated for pyelonephritis in-hospital but developed ventricular fibrillation (VF) and cardiac arrest. Electrocardiogram was normal except QTc prolongation. She underwent emergent cesarean section. Coronary CT revealed an anomalous circumflex with retro-aortic non-malignant course without dissection. Coronary angiogram without obstructive coronary disease. Cardiac magnetic resonance imaging (cMRI) revealed mid myocardial antero-lateral wall late gadolinium enhancement with normal left and right ventricular size and function. Comprehensive genetic testing revealed only a DSP missense variant ((c.1483G>A). She wore a LifeVest™ and prescribed Nadolol. One year later she again experienced chest pain and suffered an aborted cardiac arrest due to VF. Coronary angiogram showed spasm which resolved with intracoronary nitroglycerin, and she agreed to receive an implantable cardioverter defibrillator (ICD). Two years later she again suffered chest pain and had a third cardiac arrest due to VF which required 7 shocks to terminate. The circumstances were concerning for coronary spasm and she was treated with diltiazem, isosorbide, and atorvastatin. One week later she developed non-ST elevation myocardial infarction and was found at repeat catheterization to have a fixed mid-LAD stenosis refractory to intracoronary nitroglycerin which required one drug-eluting stent. This triad of recurrent chest pain, elevated cardiac enzymes and recurrent VT is suggestive of malignant vasospasm. Vasodilators such as calcium channel blockers and nitrates are critical for treatment, however ICD implantation or coronary revascularization may be warranted in refractory cases. The relationship between this patient's DSP mutation and her clinical presentation is unknown. However, her presentation bears a striking resemblance to that reported in some patients with DSP cardiomyopathy, characterized as an inflammatory cardiomyopathy with late gadolinium enhancement on cMRI, ventricular arrhythmias, and episodic chest pain in the absence of coronary artery disease. This suggests that there may be an unrecognized relationship between coronary vasospasm and the episodic chest pain noted in patients with the DSP mutation, which warrants further investigation. Therapy is limited for refractory coronary vasospasm leading to ventricular arrhythmia and sudden death. Mutations in Desmoplakin (DSP) have been described as a distinct form of arrhythmogenic cardiomyopathy characterized by chest pain and ventricular arrhythmia. Case: A healthy 31-year-old white female presented at 24 weeks gestation with flank pain and substernal chest pain. She was treated for pyelonephritis in-hospital but developed ventricular fibrillation (VF) and cardiac arrest. Electrocardiogram was normal except QTc prolongation. She underwent emergent cesarean section. Coronary CT revealed an anomalous circumflex with retro-aortic non-malignant course without dissection. Coronary angiogram without obstructive coronary disease. Cardiac magnetic resonance imaging (cMRI) revealed mid myocardial antero-lateral wall late gadolinium enhancement with normal left and right ventricular size and function. Comprehensive genetic testing revealed only a DSP missense variant ((c.1483G>A). She wore a LifeVest™ and prescribed Nadolol. One year later she again experienced chest pain and suffered an aborted cardiac arrest due to VF. Coronary angiogram showed spasm which resolved with intracoronary nitroglycerin, and she agreed to receive an implantable cardioverter defibrillator (ICD). Two years later she again suffered chest pain and had a third cardiac arrest due to VF which required 7 shocks to terminate. The circumstances were concerning for coronary spasm and she was treated with diltiazem, isosorbide, and atorvastatin. One week later she developed non-ST elevation myocardial infarction and was found at repeat catheterization to have a fixed mid-LAD stenosis refractory to intracoronary nitroglycerin which required one drug-eluting stent. This triad of recurrent chest pain, elevated cardiac enzymes and recurrent VT is suggestive of malignant vasospasm. Vasodilators such as calcium channel blockers and nitrates are critical for treatment, however ICD implantation or coronary revascularization may be warranted in refractory cases. The relationship between this patient's DSP mutation and her clinical presentation is unknown. However, her presentation bears a striking resemblance to that reported in some patients with DSP cardiomyopathy, characterized as an inflammatory cardiomyopathy with late gadolinium enhancement on cMRI, ventricular arrhythmias, and episodic chest pain in the absence of coronary artery disease. This suggests that there may be an unrecognized relationship between coronary vasospasm and the episodic chest pain noted in patients with the DSP mutation, which warrants further investigation.