A 69-year-old female Korean patient was initially prescribed warfarin for the prevention of systemic thromboembolism due to atrial fibrillation. One month later, multiple bruises and subcutaneous hematomas were evident, and laboratory testing revealed a prolonged prothrombin time (PT) of > 106s. After admission, the PT was corrected via fresh frozen plasma transfusion and intravenous vitamin K infusion. We sought to determine the cause of the PT prolongation, suspecting that genetic cause may have had an effect on the variation in the warfarin dose requirement. A point-of-care gene test device (Verigene(R) system; Nanosphere, Northbrook, IL) revealed CYP2C9*1/*3 heterozygosity and a VKORC1 A/A single nucleotide polymorphism. Although it is well established that CYP2C9 or VKORC1 gene polymorphisms can influence warfarin dose requirements, they can be easily neglected, with detrimental outcomes. Through our experience with CYP2C9 and VKORC1 polymorphism causing bleeding complications during warfarin treatment, we aim to emphasize the importance of pharmacogenetic testing to avoid this potential oversight.
Atrial Fibrillation ; Contusions ; Female ; Hematoma ; Hemorrhage ; Humans ; Nanospheres ; Pharmacogenetics ; Plasma ; Point-of-Care Systems ; Polymorphism, Single Nucleotide ; Prothrombin Time ; Thromboembolism ; Vitamin K ; Warfarin

BACKGROUND AND OBJECTIVES: Cardiac troponins are associated with increased mortality, even among patients with no coronary artery disease. Elevated cardiac troponin levels are frequently observed in patients without significant coronary lesions, although the mechanism underlying this finding is unclear. The aim of our study was to evaluate the association between the levels of cardiac troponin and coronary flow reserve (CFR). SUBJECTS AND METHODS: We evaluated serum cardiac troponin-I in 19 patients (9 female; age 61.9+/-10.9 year-old). All patients had an ejection fraction >40% and angiographically normal coronary arteries. Simultaneous measurements of fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and CFR measurements using an intracoronary temperature- and pressure-sensing guidewire under basal conditions and during maximal hyperemia were performed in three vessels: the left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). RESULTS: All patients were followed for a median of 13 months. FFR, IMR, and CFR measurements were performed successfully in all subjects. Mean CFRs of LAD, LCX, and RCA were 1.98+/-1.20, 2.75+/-2.11, and 4.44+/-2.51, respectively. Mean IMRs of LAD, LCX and RCA were 33.28+/-18.78, 29.11+/-26.70, and 30.55+/-23.65, respectively. There was a poor correlation between CFR and troponin-I values in each vessel. In selecting the lowest value of CFR in each patient as the corresponding value, the lowest CFR was not associated with troponin-I levels (r=-0.219, p=0.367). CONCLUSION: In patients without significant coronary lesions, the correlation between CFR and troponin-I level was not significant using a thermodilution technique. Further study of a larger population with longer-term follow-up may be needed to more fully understand microvascular dysfunction.
Arteries ; Coronary Artery Disease* ; Coronary Vessels ; Female ; Follow-Up Studies ; Humans ; Hyperemia ; Microvessels ; Mortality ; Thermodilution* ; Troponin I ; Troponin* ; Vascular Resistance

The differential diagnosis of cardiac mass is important in determining the therapeutic plan and avoiding unnecessary surgical intervention. Non-invasive imaging methods would be useful in the diagnosis of suspected cardiac mass, because they may provide earlier diagnosis and more accurate assessment of cardiac mass. Native aortic valve thrombosis is a rare disorder and difficult to differentiate from a tumor, and in particular, a papillary fibroelastoma. Thus, the clinical decision making with imaging modalities should be performed cautiously. We recently met a female patient who had a aortic valve mass resembling papillary fibroelastoma in normal native valve. The patient underwent a surgical resection and the pathologic finding showed an organized thrombus with no evidence of papillary fibroelastoma.
Aortic Valve* ; Decision Making ; Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Pulmonary Embolism ; Thrombosis*

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥ 2 mm thick, high echogenicity, and a peak trans-aortic velocity of < 2.5 m/sec) and an age- and sex-matched control group were enrolled.Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6 ± 8.5 yrs, and 54.5% were male. An average of 1.3CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of≥ 0.5%, was similar between the groups. However, the AVS group had larger CHIP clones:49 (39.2%) participants had a VAF of ≥ 1% (vs. 13 [21.0%] in the control group; P = 0.020), and 25 (20.0%) had a VAF of ≥ 2% (vs. 4 [6.5%]; P = 0.028). AVS is independently associated with a VAF of ≥ 1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11–5.36; P = 0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

Background and Objectives: Severe aortic stenosis (AS) with left ventricular systolic dysfunction (LVSD) is a class I indication for aortic valve replacement (AVR) but this recommendation is not well established in those at the stage of moderate AS. We investigate the clinical impact of AVR among patients with moderate AS and LVSD. Methods: From 2001 to 2017, we consecutively identified patients with moderate AS and LVSD, defined as aortic valve area 1.0–1.5 cm2 and left ventricular ejection fraction <50%. The primary outcome was all-cause death. The outcomes were compared between those who underwent early surgical AVR (within 2 years of index echocardiography) at the stage of moderate AS versus those who were followed medically without AVR at the outpatient clinic. Results: Among 255 patients (70.1±11.3 years, male 62%), 37 patients received early AVR. The early AVR group was younger than the medical observation group (63.1±7.9 vs. 71.3±11.4) with a lower prevalence of hypertension and chronic kidney disease. During a median 1.8-year follow up, 121 patients (47.5%) died, and the early AVR group showed a significantly lower all-cause death rate than the medical observation group (5.03PY vs. 18.80PY, p<0.001). After multivariable Cox-proportional hazard regression adjusting for age, sex, comorbidities, and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of death (hazard ratio, 0.43; 95% confidence interval 0.20–0.91; p=0.028). Conclusions In patients with moderate AS and LVSD, AVR reduces the risk of all-cause death. A prospective randomized trial is warranted to confirm our findings.

Background: This study aimed to investigate the cardiac manifestations of coronavirus disease 2019 (COVID-19). Methods: From February to March 2020, we prospectively and retrospectively enrolled consecutive patients diagnosed with COVID-19. Patient's data such as the demographic characteristics, symptoms, vital signs, laboratory and radiologic findings, electrocardiographic, and echocardiographic data, including the global longitudinal strain (GLS) of both ventricles, were obtained. Results: Forty patients (median age, 58 years; 50% men) were enrolled in the initial analysis. Patients were classified into severe and nonsevere groups based on the current guidelines. The 13 patients in the severe group were significantly older, had a greater prevalence of bilateral pneumonia and leukocytosis, and higher aspartate transaminase levels than patients in the nonsevere group. Patients in the severe group had a slightly lower left ventricular ejection fraction (LVEF) than those in the nonsevere group (median [interquartile range], 61.0% [58.5%, 62.3%] vs. 66.7% [60.6%, 69.8%], P = 0.015). In a subgroup of 34 patients in whom GLS could be analyzed, patients in the severe group had a significantly impaired left ventricular GLS (LVGLS) than those in the nonsevere group (−18.1% [−18.8%, −17.1%] vs. −21.7% [−22.9%, −19.9%], P = 0.001). There were no significant differences in total wall (RVGLS total , −19.3% [−23.9%, −18.4%] vs. −24.3% [−26.0%, −22.6%], P = 0.060) and free wall (RVGLS fw , −22.7% [−27.2%, −18.6%] vs. −28.8% [−30.4%, −24.1%], P = 0.066) right ventricle GLS (RVGLS). Conclusion Patients with severe COVID-19 had lower LVEF and LVGLS. RVGLS was not different between patients with severe and nonsevere COVID-19.