Hypertensive patients with concentric remodeling (relative wall thickness > or = 0.45 and normal left ventricular [LV] mass index) may have poor outcomes. It is unclear whether systolic function abnormalities, shown to be present in some patients with concentric LV hypertrophy (increased LV mass index and relative wall thickness > or = 0.45), are also present in patients with concentric remodeling. To assess LV pump, chamber, and myocardial function in hypertensive men with concentric remodeling, clinical and echocardiographic data of 118 hypertensive men with concentric remodeling were compared with data from 104 hypertensive men with normal relative wall thickness and normal LV mass index. Chamber function was assessed by relating endocardial fractional shortening to end-systolic circumferential stress, myocardial function was assessed by relating midwall fractional shortening to circumferential stress, and pump performance was assessed by stroke volume (Teichholz method). Compared with hypertensive men with normal relative wall thickness, concentric-remodeling patients had lower stroke volume (84 +/- 20 versus 111 +/- 20 mL, P < .001). Endocardial shortening was no different between the two groups (38 +/- 7% versus 40 +/- 7%, P=NS), but midwall shortening was lower in patients with concentric remodeling (20 +/- 3% versus 22 +/- 3%, P < .001), despite lower end-systolic stress (81 +/- 25 versus 117 +/- 37 g/cm2, P < .001). Endocardial and midwall stress-shortening regression plots classified 28% and 42%, respectively, of the concentric remodeling patients below the fifth percentile of hypertensive patients with normal geometry. These data indicate that indexes of chamber and myocardial function are lower than those observed in hypertensive patients with normal geometry. Thus, indices of chamber, myocardial, and pump performance indicate potential abnormalities in systolic function in men with concentric remodeling.
Background
Pembrolizumab, an immune checkpoint inhibitor (ICI), is an IgG4 antibody that blocks interaction between programmed cell death protein 1 and programmed death-ligand 1. Myocarditis, an immune-related adverse event, has been reported in thymic epithelial tumours. Pembrolizumab has also been associated with development/exacerbation of myasthenia gravis (MG).
Case summary
A 70-year-old woman with metastatic thymic cancer presented to the hospital with shortness of breath, 21 days after initiation of pembrolizumab. She was diagnosed with ICI-related myocarditis and was subsequently intubated due to respiratory failure. A dual-chamber pacemaker was placed due to complete heart block with asystole. Her troponin levels were elevated, an electrocardiogram was suspicious for myocardial infarction, but coronary angiogram revealed normal coronary arteries and endomyocardial biopsy confirmed the presence of myocarditis. Treatment was started with high-dose intravenous methylprednisolone and cardiovascular status improved. However, the patient was unable to be weaned from mechanical ventilation and tested positive for acetylcholine receptor binding/blocking antibodies due to de novo MG. After 50 days of hospitalization, she was discharged home in stable condition. A computed tomography scan was performed 6 weeks after pembrolizumab; results showed significant decrease/resolution of all measurable sites of metastatic disease in the lungs.
Discussion
This is the first reported case of a patient developing single-agent pembrolizumab-induced myocarditis concomitant with new-onset MG after treatment for advanced thymic malignancy. Additional studies are needed to explore the association between myocarditis, MG, and ICI therapy.
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