Acute coronary thrombosis due to heparin-induced thrombocytopenia following improved COVID-19 pneumonia: A case report.

A 45-year-old male with anteroseptal myocardial infarction was referred to our hospital. The patient was previously admitted to another hospital with coronavirus disease-2019 pneumonia for 2 weeks; he was discharged 2 weeks before presentation to our institution. He received conventional treatment for coronavirus disease-2019, including administration of heparin. A moderate decrease in platelet count was observed on admission, and emergent angiography was performed under a definitive diagnosis of acute coronary syndrome. The angiography revealed occlusion of the left anterior descending artery. Percutaneous coronary intervention was performed; however, the occlusion did not improve owing to persistent thrombosis in the distal left anterior descending artery. Therefore, we induced intra-aortic balloon pumping to improve coronary blood flow and obtained Thrombolysis in Myocardial Infarction grade 2 flow. Following percutaneous coronary intervention, we detected a further decrease in platelets and positivity for heparin-induced thrombocytopenia antibody, leading to the diagnosis of heparin-induced thrombocytopenia. Subsequently, oral anticoagulation was introduced, and the symptoms did not recur. Learning objective: Treatment with heparin is indicated for patients with coronavirus disease-2019 (COVID-19) because of derangement of the coagulation system. However, this approach contributes to the development of heparin-induced thrombocytopenia (HIT). We report a case of acute coronary syndrome due to HIT with COVID-19. HIT is commonly reported in patients with COVID-19. Thus, attentive monitoring of the platelet count and considering the possibility of HIT are indispensable when treating acute coronary syndrome in patients with previous history of COVID-19.

Discontinuation of Cardiac Resynchronization Therapy for Heart Failure Due to Dilated Cardiomyopathy in a 61-Year-Old Female "-Super-Responder" with Return of a Reduced Left Ventricular Ejection Fraction to Normal.

BACKGROUND Although cardiac resynchronization therapy (CRT) is widely used, it has been validated only during active pacing. "Super-responders" are patients with normalized or markedly improved left ventricular (LV) systolic function with CRT who may experience a decline in cardiac function with CRT discontinuation. CASE REPORT A 61-year-old woman with a nonischemic cardiomyopathy was admitted to our hospital in September 2008 for the treatment of heart failure (HF). Cardiac assessment revealed impaired LV function with an ejection fraction of 18%, LV dilatation, and left bundle branch block (LBBB). Despite optimized medical treatment, her HF progressed, with a rapid increase in LV chamber size, mitral regurgitation, and widening of the QRS complex. In July 2011, the patient initially refused CRT, but later consented to the procedure; CRT pacemaker implantation was subsequently performed. Thereafter, the LVEF improved from 27% to 46%, LV diastolic dimension decreased rapidly from 79 mm to 56 mm, and LVEF (65%) and LV size (47 mm) normalized within 1 year later. As of August 2012, battery exchange was needed within 1 year because of high LV pacing thresholds. In October 2012, although CRT discontinuation was not recommended, we discontinued CRT to conserve battery life with the patient's consent, hoping to maintain her condition with pharmaceutical treatment. She remained stable through January 2020, with no indication of re-exacerbation. CONCLUSIONS We describe a female patient with a nonischemic cardiomyopathy and LBBB who demonstrated a super-response to CRT and maintained improvement in LV function and functional status for 8 years after discontinuing CRT.

Apixaban for the treatment of cancer-associated venous thromboembolism and left atrial appendage thrombus refractory to optimal anticoagulation with warfarin: a case report.

BACKGROUND: Concomitant venous thromboembolism (VTE) and left atrial appendage (LAA) thrombus associated with cancer is exceedingly rare. The use of direct factor Xa inhibitors in patients with cancer is controversial. CASE SUMMARY: We report a rare case of concomitant VTE and LAA thrombus in an 85-year-old man with prostate cancer. He developed VTE and LAA thrombus, while on warfarin therapy for non-valvular atrial fibrillation. Despite optimal medical treatment with warfarin, systemic thrombosis developed. After thrombolysis, he was prescribed apixaban, an oral direct factor Xa inhibitor, as maintenance therapy. Deep venous thrombosis, pulmonary embolism, and LAA thrombus were effectively treated, and his symptoms resolved. DISCUSSION: Despite the fact that many patients with cancer are in a hypercoagulable state, to the best of our knowledge, this is a first case describing VTE and LAA thrombus presenting concomitantly during optimal warfarin therapy. This case demonstrates the importance of awareness of systemic thrombosis in patients with cancer regardless of vitamin K antagonist therapy. More cases and larger scale data are needed to investigate if factor Xa inhibitors are useful for treating systemic thrombosis in patients with cancer.

Acute compartment syndrome occurring in forearm with relatively small amount of hematoma following transradial coronary intervention.

A 59-year-old female with angina pectoris successfully underwent percutaneous coronary intervention via the right radial artery. She complained of right forearm pain and numbness 4.5 h after the procedure. Though the swelling in her right arm seemed relatively mild, pressure measurement showed significant increase of internal forearm pressure. She developed acute compartment syndrome in the right forearm, and fasciotomy was performed immediately. The weight of subcutaneous hematoma in her right arm was approximately 100 g. Symptoms of paralysis and the impairment of perception remained for some time, but had completely recovered 4 months post-surgery.

Potential difficulty for accurate categorization of drug-eluting stent thrombosis without coronary angiography: unignorable involvement of the cases with new onset acute myocardial infarction occurred in target vessels.

Very late stent thrombosis (VLST) is a major unresolved problem of drug-eluting stent (DES) implants. However, its actual incidence with respect to the distribution of DES-target vessel and accuracy of adjudicating stent thrombosis according to the ARC definition has not been yet adequately evaluated. We studied 720 patients who had completed over 1 year from elective DES implantation. In this cohort, we extracted patients who present acute coronary syndrome (ACS) (n = 3, 0.4%). The timing of ACS events was 17, 19, and 24 months after DES implantation. At the time of presentation, VLST was strongly suspected as the initial diagnosis, however, coronary angiography (CAG) confirmed the different culprit lesion from DES and clearly no thrombus within the DES. According to ARC definition, three probable stent thromboses in this cohort before CAG, however, no stent thrombosis was confirmed after the CAG. Thus, no stent thrombosis was confirmed among this study population. In the very late phase after DES implantation, new onset ACS is not at all extraordinary occurrence in the target vessels of previous DES implantation. However, stent thrombosis is often assumed without angiographic confirmation. The clinical possibility that non-stent thrombosis is incidentally diagnosed with stent thrombosis without angiographic confirmation should be considered within the current accepted definition of stent thrombosis.

Stent implantation for diffuse and multiple coronary spasm in a patient with variant angina refractory to optimal medical therapy.

A patient with variant angina presented complaining of frequent morning chest pain refractory to maximal doses of 5 vasodilator agents. His condition was complicated by a drug eruption due to a side effect of the calcium antagonist. Coronary angiography showed no organic stenosis, but a challenge test revealed multiple and diffuse coronary artery spasms at the right coronary artery and the left anterior descending artery. A total of 5 stents were implanted for full coverage of the spastic segments. Spasm could not be provoked by repeating the challenge test after stenting. He has been asymptomatic for 8 months since the procedure.

Nicotine enlivenment of blood flow recovery following endothelial progenitor cell transplantation into ischemic hindlimb.

Nicotine has been demonstrated to stimulate postnatal angiogenesis, having an antiapoptotic effect on endothelial cells. Given the extent of this angiogenesis-promoting effect, we hypothesized that nicotine may also stimulate postnatal vasculogenesis on endothelial progenitor cells (EPCs). Our analyses reveal some intriguing results using an in vitro assay with 2 x 10(-6) M of nicotine (smoker's average nicotine concentration and the dose of nicotine replacement therapy). The proliferation and migration activities of human EPCs cultured from peripheral blood mononuclear cells of non-smoking healthy volunteers were not affected by nicotine. The effect of nicotine on EPC survival was significantly enhanced under serum starvation on the ratio of Hoechest 33342-stained pyknotic nuclear cells as well as Annexin-V-stained cells to total cells. Furthermore, the antiapoptotic effect of nicotine was blocked completely by nicotinic acetylcholine receptor (nAChR) antagonist hexamethonium. Next, we verified how nicotine acts in vivo. Nicotine (100 ng/ml) was administered orally for 7 days before and 4 weeks after injection of cultured EPCs (1 x 10(5) /mouse) into the tail veins of 8-week-old athymic nude mice with ischemic hindlimbs. Laser doppler imaging analysis indicated that blood perfusion in the ischemic hindlimb was significantly enhanced in EPCs plus nicotine, as compared with EPCs alone. These findings suggest nicotine improves blood flow following EPC transplantation in patients with ischemic diseases.

Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis.

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta. Under the physiological concentrations of estrogen (17beta-estradiol, E2), proliferation and migration were stimulated, whereas apoptosis was inhibited on day 7 cultured EPCs. These estrogen-induced activities were blocked by the receptor antagonist, ICI182,780 (ICI). In BM transplanted (BMT) mice with ovariectomy (OVX) from transgenic mice overexpressing beta-galactosidase (lacZ) regulated by an endothelial specific Tie-2 promoter (Tie-2/lacZ/BM), the uterus demonstrated a significant increase in BM-derived EPCs (lacZ expressing cells) incorporated into neovasculatures detected by CD31 immunohistochemistry after E2 administration. The BM-derived EPCs that were incorporated into the uterus dominantly expressed ER alpha, rather than ER beta in BMT mice from BM of transgenic mice overexpressing EGFP regulated by Tie-2 promoter with OVX (Tie-2/EGFP/BMT/OVX) by ERs fluorescence immunohistochemistry. An in vitro assay for colony forming activity as well as flow cytometry for CD133, CD34, KDR, and VE-cadherin, using human PB-MNCs at 5 stages of the female menstrual-cycle (early-proliferative, pre-ovulatory, post-ovulatory, mid-luteal, late-luteal), revealed cycle-specific regulation of EPC kinetics. These findings demonstrate that physiological postnatal vasculogenesis involves cyclic, E2-regulated bioactivity of BM-derived EPCs, predominantly through the ER alpha.

Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest.

BACKGROUND: Because nifekalant hydrochloride (NIF) displayed a superior defibrillating effect on ventricular tachycardia/fibrillation (VT/VF) in cardiopulmonary arrest (CPA) patients, despite some QT prolongation, its effect on transmural dispersion of repolarization (TDR) in the left ventricle (LV) in an animal model of CPA was investigated. METHODS AND RESULTS: Eight beagle dogs were created with a myocardial infarction under anesthesia, and then VT/VF induction by continuous stimulation and cardiopulmonary resuscitation (CPR) were repeated. NIF (0.3 mg/kg) was administered under acidotic conditions (pH 7.26). The QTc interval measured by Y-lead ECG showed no significant prolongation before and after NIF. The activation recovery interval (ARI) measured by 64-lead LV surface mapping showed minimum ARI prolongation (40%) by NIF without maximum ARI prolongation, and as a result the ARI dispersion decreased by 67%. The repolarization time (RPT) with the plunge electrode showed 13-19% prolongation in the subendocardium and subepicardium with CPR, but NIF prolonged the RPT in the middle layer alone (17%), and as a result Plunge-TDR decreased by 82% (n=8, p<0.05). CONCLUSIONS: Administration of NIF during CPR decreased the TDR by RPT prolongation selectively in the middle layer. Because the subendocardial and subepicardial RPTs after CPR were already prolonged before NIF administration, it may have been the reason why the QT-prolonging effect of NIF was not reflected in the body surface ECG.

Can nifekalant hydrochloride be used as a first-line drug for cardiopulmonary arrest (CPA)? : comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis.

BACKGROUND: Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I(Kr) blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. METHODS AND RESULTS: The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. CONCLUSIONS: NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR.