Life-threatening coronary vasospasm in patients with type 2 diabetes with SGLT2 inhibitor-induced euglycemic ketoacidosis: a report of two consecutive cases.

Euglycemic diabetic ketoacidosis (eDKA) has emerged as an adverse event associated with sodium-glucose transporter-2 inhibitors (SGLT2i). We present two consecutive cases of SGLT2i-induced eDKA, both manifested as life-threatening coronary vasospastic angina (VSA). Case 1: A 64-year-old male overweight patient with type 2 diabetes (BMI 28.2 kg/m2), treated with dapagliflozin 5 mg daily for 6 months and a restricted diet for 2 months, experienced loss of consciousness following severe chest pain while driving, resulting in a traffic accident: plasma glucose, 163 mg/dL; urine ketones, (+++); bicarbonate (HCO3-), 13.2 mmol/L; and total ketone body, 1539 µmol/L. Coronary angiography (CAG) performed on day 5 revealed diffusely spastic coronary arteries with 90% stenosis in the right coronary artery, leading to the diagnosis of VSA in the presence of coronary atherosclerosis. Case 2: A 63-year-old male patient with type 2 diabetes (BMI 22.2 kg/m2) experienced severe chest discomfort and faintness following 2 months of chest pain while on dapagliflozin 10 mg daily for 1 year: plasma glucose, 112 mg/dL; urine ketones, (+++); HCO3-, 15.3 mmol/L; and total ketone body, 10,883 µmol/L. CAG performed on day 10 revealed no organic stenosis but diffusely spastic coronary arteries in response to coronary ergonovine infusion, confirming the diagnosis of VSA. SGLT2i has the potential to inhibit acetylcholine and butyrylcholine esterase activities, leading to reduced scavenging of acetylcholine and possible induction of coronary vasospasm. These cases highlight the association between life-threatening VSA and SGLT2i-induced eDKA.

Coronary artery stenting in a patient with factor XI deficiency.

Factor XI deficiency is a rare inherited coagulopathy first described in Ashkenazi Jews. In Japanese populations, factor XI deficiency is thought to be very rare. This disorder causes unique problems during percutaneous coronary intervention (PCI). During PCI, prevention of thrombosis is important and heparin is usually used for anticoagulation. However, care must also be taken to avoid serious complications of bleeding. These two situations are contradictory and anticoagulation with heparin might increase severe bleeding in patients with factor XI deficiency. An 84-year-old Japanese woman was admitted to our hospital for the treatment of worsening effort angina pectoris. A coronary angiography revealed severe stenotic lesions at the left main trunk (LMT) and the right coronary artery (RCA). While performing PCI of the LMT, 8,000 U of heparin were used and the patient underwent successful drug-eluting stent implantation. At this point, the patient's activated coagulation time was over 1,500 s and there was a marked decrease of factor XI activity (<3%: normal range 75-145%). After the diagnosis of factor XI deficiency, PCI for the RCA was scheduled without anticoagulation and fresh frozen plasma instead of dual antiplatelet therapy by aspirin and clopidogrel. Two drug-eluting stents were deployed and dilation using the kissing balloon technique was performed. The procedure was uneventful without stent thrombosis or distal embolization or bleeding. Because the literature on stenting for patients with factor XI deficiency is very limited, this case provides additional clinical information.

A case of acute myocardial infarction with repetitive stent thrombosis during emergent percutaneous coronary intervention. Transient decrease in antithrombin III activity and heparin resistance.

A 59-year-old woman was admitted to our hospital for the treatment of an acute anterior myocardial infarction. She had a history of uncontrolled diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking. Coronary angiography revealed 90% stenosis with spontaneous dissection in the proximal portion of the left anterior descending artery. At this time, heparin was initiated for the first time. Although direct stenting (Be-stent, 3.0-18 mm) was performed for the culprit lesion, coronary dissection occurred at the left main trunk and additional stenting (Multi Link ZETA stent 3.5-15mm) was performed for the left main trunk. Soon after stenting, repetitive stent thrombosis occurred. Aspiration of the thrombus using an aspiration catheter was ineffective and repetitive angioplasty and intraaortic balloon pumping were required. Although we used 17,000 units of unfractionated heparin during the intervention, the activated coagulation time (ACT) was not prolonged (157 seconds). In the coronary care unit, the ACT and activated partial prothrombin time (aPTT) were not prolonged despite the use of large amounts of heparin (69,000 units in 2 days). Protein-S, protein-C, and hepaplastin testing were within normal limits and heparin-platelet factor IV complex antibody was not detected. In the acute phase, a decrease in the antithrombin III activity (65%) was noted and with administration of argatroban, prolongation of the aPTT was achieved. In the chronic phase, the decrease in antithrombin III activity and heparin resistance had improved spontaneously. It is important to recognize the existence of transient decreases in antithrombin III activity in the acute phase of myocardial infarction.

Persistent left bundle branch block in a patient with dilated cardiomyopathy that improved with low dose carvedilol therapy.

A 43-year-old Japanese woman with dilated cardiomyopathy had complete left ventricular bundle branch block (CLBBB), which had persisted for at least two years. At the time of admission, the serum brain natriuretic peptide (BNP) concentration was 502 pg/mL (normal range, 0-18 pg/mL), the left ventricular diastolic dimension (LVDd) was 59 mm, the left ventricular systolic dimension (LVDs) was 54 mm, the %fractional shortening (FS) was 8%, and the left ventricular ejection fraction (LVEF) was 19.7% by echocardiography. Low dose carvedilol was initiated for the treatment of heart failure. Adverse effects, such as progression of cardiac conduction disturbances, did not occur after initiation of carvedilol therapy. About one year after initiation of carvedilol therapy, the CLBBB disappeared and a significant improvement in left ventricular function was noted. The LVDd was 44 mm, the LVDs was 30 mm, the %FS was 33%, and the LVEF was 61%, and the serum BNP concentration was decreased to 18.5 pg/mL. We describe a case in which low dose carvedilol was effective for treating both CLBBB and left ventricular function.

Coronary artery multistenting in the treatment of life-threatening refractory coronary spasm after coronary artery bypass grafting.

A 74-year-old man had undergone on-pump coronary artery bypass grafting (CABG) for effort-induced angina pectoris. Soon after CABG using the left internal thoracic artery for the left anterior descending artery and saphenous vein for the left circumflex artery, ST elevation was found in the inferior leads and complete atrioventricular block, ventricular tachycardia, and circulatory collapse occurred. Emergent coronary angiography revealed diffuse severe spasm of the right coronary artery (RCA). Despite the intravenous and intracoronary administration of massive doses of vasodilators and intra-aortic balloon pumping, the coronary spasm did not resolve. Five stents were deployed from the distal to the proximal portion of the RCA. After multistenting, coronary flow was dramatically improved and the ST elevations in the inferior leads were also improved. Coronary artery spasm after CABG is relatively rare, but when it occurs, it can be fatal. Multistenting is a useful treatment for life-threatening refractory coronary spasm after CABG.