Clinically unrecognized moderate MR is prevalent in "lone" AF -either as an etiologic factor leading to "lone" AF or developing after onset of AF.

Dabigatran etexilate mesylate, a direct thrombin inhibitor, has been approved in the United States as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. The authors report 2 cases of development of large left atrial thrombi and unfortunate occurrence of thromboembolic events in patients with chronic atrial fibrillation, despite these patients being compliant with recommended dabigatran therapy. The authors postulate that certain unique pharmacologic characteristics of the drug may be disadvantageous toward providing a therapeutic level of anticoagulation in all patients and may provide an explanation of occurrence of these thrombotic events, namely, (1) a competitive, reversible, and incomplete inhibition of only one coagulation factor (thrombin), as opposed to warfarin that leads to noncompetitive inhibition of multiple coagulation factors, (2) a short half-life (12-17 hours) and linear pharmacodynamics related to drug levels that conceivably causes an hourly variation of the level of anticoagulation, (3) a much lower incidence of supratherapeutic anticoagulation ("overshoot") with dabigatran as compared with warfarin, and (4) a reported increase in the coagulation factors that follows long-term use of dabigatran. Also, the absence of routine monitoring to test the therapeutic efficacy of the drug prevents diagnosis of cases where anticoagulation remains subtherapeutic. These factors could explain occurrence of the thrombotic and thromboembolic events in our cases.

The authors describe 2 cases of extensive intracoronary thrombus formation leading to acute closure of the left main where bivalirudin (Angiomax) was used as the anticoagulant during percutaneous coronary intervention leading to mortality. Both cases had similarity in the cascade of complications of coronary dissection leading to slow flow and prolonged procedure time with compromise of antegrade flow in the coronary artery and a final catastrophic development of extensive intracoronary thrombosis extending into the left main and nonintervened vessel (left anterior descending or circumflex) followed by ventricular fibrillation and death. Bivalirudin has reversible anticoagulant pharmacodynamics because the bivalirudin molecule is cleaved by the thrombin molecule. In situations when the antegrade flow is compromised, delivery of fresh circulating bivalirudin to replenish the catalysis of bivalirudin by thrombin is diminished, allowing thrombin activity to regenerate, thereby creating a prothrombotic milieu in these coronary segments. This can lead to extensive intracoronary thrombus formation in situations of slow flow precipitated by coronary dissection and prolonged dwell time with intracoronary hardware (wires, balloons, and stents). Interventionalists should be aware of the potential risk of this fatal complication and should be proactive in recognizing the scenarios where this is likely to occur. In such anticipated circumstances, the interventionalist may judiciously switch the anticoagulant to heparin and/or use additional glycoprotein IIb/IIIa inhibitor because freshly formed intracoronary thrombus is susceptible to lysis by glycoprotein IIb/IIIa inhibitors.

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