When Virchow’s Triad Goes on Overdrive: Catastrophic Multi-System Thrombosis in the Setting of New-Onset Heart Failure in a Previously Healthy Man

Catastrophic multi-territory thromboembolism is an uncommon but life-threatening presentation that often signals an underlying hypercoagulable state or severe cardiac dysfunction. When all three components of Virchow’s triad converge simultaneously in a previously healthy individual, the clinical consequences can be devastating and the diagnostic workup both urgent and complex. We report a 58-year-old man with no prior medical history who presented with progressive dyspnea and was found to have bilateral pulmonary emboli, large mobile thrombi in both the left atrium and left ventricle, and extensive systemic arterial thrombosis culminating in left lower extremity ischemia. Imaging revealed an underlying heart failure with reduced ejection fraction with an estimated ejection fraction of 20% and concurrent atrial flutter. Comprehensive hypercoagulable workup including antiphospholipid antibody syndrome evaluation was negative. The patient required emergent left lower extremity embolectomy at the initial hospital, transfer to a tertiary center for repeat femoral-femoral bypass that subsequently thrombosed, and ultimately a left below-knee amputation. He was discharged on apixaban. Subsequent atrial fibrillation/flutter ablation achieved durable sinus rhythm. Genetic testing revealed a pathogenic TTN (titin) variant, providing a unifying etiology for his dilated cardiomyopathy. Serial echocardiography at 3 months demonstrated resolution of all intracardiac thrombi; repeat imaging at 6 months showed substantial left ventricular ejection fraction recovery to 42%. This case illustrates that new-onset heart failure with reduced ejection fraction with concurrent atrial flutter can serve as a sufficient and independent driver of catastrophic multi-territory thromboembolism without additional systemic hypercoagulable disease. It also demonstrates that with aggressive guideline-directed medical therapy, rhythm control, and sustained anticoagulation, meaningful ventricular recovery is achievable even after severe initial dysfunction. TTN-related cardiomyopathy should be considered in otherwise unexplained dilated cardiomyopathy, and genetic counseling should be offered to first-degree relatives.