AK098656: a new biomarker of coronary stenosis severity in hypertensive and coronary heart disease patients

Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

Trans-coronary Pacing via Rota Wire Prevents Bradycardia During Rotational Atherectomy: A Case Report

Back ground Rotational atherectomy (RA) is used for plaque modification in patients with heavily calcified coronary lesions. RA can induce significant bradycardia or atrioventricular block requiring for temporary pacemaker insertion. In this report, we present a case of trans-coronary pacing via a Rota wire to prevent bradycardia during RA in the proximal right coronary artery (RCA). Case summary A 72-year-old woman with a one month history of worsening effort angina was admitted to our hospital. Computed tomography coronary angiography disclosed significant coronary stenosis with severe calcification in proximal RCA. Coronary angiography revealed significant coronary stenosis with severe calcification in the proximal RCA. Subsequently, percutaneous coronary artery intervention was performed under the guidance of intravascular ultrasound(IVUS). The pull-back IVUS showed a circumferential calcified lesion in the proximal RCA, that was treated using RA, which induced significant bradycardia requiring temporary pacemaker insertion. Immediately, trans-coronary pacing was provided via a Rota wire placed in the far distal RCA; this was used for back-up pacing during RA. RA was completed by safely modifying the calcified lesion. After successful debulking of the calcified lesion, we dilated with a balloon, and a drug-eluting stent was implanted at the proximal RCA. Final IVUS and angiography showed good stent apposition and expansion. we did not observe any serious intraprocedural complications. Discussion RA is used for plaque modification in patients with heavily calcified coronary lesions. RA can induce significant bradycardia or atrioventricular block requiring for temporary pacemaker insertion via the transvenous route. This method could be an effective method to prevent bradycardia during RA.

Change in Computed Tomography-Derived Fractional Flow Reserve Across the Lesion Improve the Diagnostic Performance of Functional Coronary Stenosis

Aims: This study sought to evaluate the diagnostic performance of change in computed tomography-derived fractional flow reserve (CT-FFR) across the lesion (ΔCT-FFR) for identifying ischemia lesions with FFR as the reference standard.Methods: Patients who underwent coronary CT angiography (CCTA) and FFR measurement within 1 week from December 2018 to December 2019 were retrospectively enrolled. CT-FFR within 2 cm distal to the lesion, ΔCT-FFR and plaque characteristics were analyzed. The diagnostic accuracy of CCTA (coronary stenosis ≥ 50%), CT-FFR ≤ 0.80, and ΔCT-FFR ≥ 0.15 (based on the largest Youden index) were assessed with FFR as the reference standard. The relationship between plaque characteristics and ΔCT-FFR was analyzed.Results: The specificity of ΔCT-FFR and CT-FFR were 70.8 and 67.4%, respectively, which were both higher than CCTA (39.3%) (both P < 0.001), while there were no statistical significance in sensitivity among the three (84.5, 77.4, 88.1%, respectively; P = 0.08). The area under the curves (AUCs) of ΔCT-FFR and CT-FFR were 0.803 and 0.743, respectively, which were both higher than that of CCTA (0.637) (both P < 0.05), and the AUC of ΔCT-FFR was higher than that of CT-FFR (P < 0.001). Multivariable analysis showed that low-attenuation plaque (LAP) volume (odds ratio [OR], 1.006) and plaque length (OR, 1.021) were independently correlated with ΔCT-FFR (both P < 0.05).Conclusions: CT-FFR and ΔCT-FFR and here especially the ΔCT-FFR could improve the diagnostic performance of ischemia compared with CCTA alone. LAP volume and plaque length were the independent risk factors of ΔCT-FFR.

Late-Onset Ictal Asystole and Falls Related to Severe Coronary Artery Stenosis: A Case Report

Introduction: Ictal asystole (IA) is a rare, underestimated, and life-threatening cause of transient loss of consciousness and fall. Current treatment options for seizures associated with IA usually include cardiac pacemaker implantation. We report, for the first time, a case of IA that is related to coronary stenosis, which was resolved after coronary angioplasty.Case Presentation: A 73-year-old man had a 2-year history of focal seizures with impaired awareness. Three months before our observation, he started to have sudden falls resulting in injury on several occasions. General and neurological examinations, as well as brain MRI, were unremarkable. Interictal electroencephalography (EEG) showed bitemporal spiking. Ictal video-polygraphy revealed a diffuse electrodecrement, followed by a buildup of rhythmic 4–6 Hz sharp activity, which was more evident in the left temporal region. After the seizure onset, the ECG showed sinus bradycardia, followed by sinus arrest that was associated with the patient's fall from the standing position. Afterwards, sinus rhythm returned spontaneously. A diagnosis of IA was made. A comprehensive cardiologic evaluation revealed a sub-occlusive stenosis of the left anterior descending artery. Successful coronary angioplasty resolved IA, levetiracetam was added, and no seizure or fall has occurred in the following 20 months. Moreover, he underwent a 7-day Holter ECG monitoring, and no asystole was depicted.Conclusion: The present case was unique as it shows the potential association between IA and coronary stenosis, also suggesting a possible therapeutic role for coronary angioplasty. It also highlights the importance of carefully investigating epilepsy patients with falls, especially in the elderly, since IA-related falls can be easily misdiagnosed in older age. Thus, if IA is identified, a deeper cardiac evaluation should be considered. As seen in our patient, non-invasive diagnostic examination including routine, prolonged, and exercise ECG, as well as echocardiogram, were readily available and were informative in diagnosing cardiac abnormalities that are amenable to specific treatment.

Low Serum Calcitonin Gene-Related Peptide Level is Associated with Severity of Coronary Stenosis

Purpose: To evaluate the relationship between the serum calcitonin gene-related peptide (CGRP) level and severity of coronary stenosis. Methods: A total of 233 eligible patients who underwent coronary angiography were divided into two groups: a control and a coronary heart disease (CHD) group. The angiographic severity of coronary stenosis was evaluated by SYNTAX and Gensini scores. The incidence of major adverse cardiovascular events within two years was collected. Results: A negative correlation between serum CGRP levels and Gensini scores was observed in all patients (r=-0.352, p<0.001), the control group (r=-0.422, p<0.001) and the CHD group (r=-0.393, p<0.001). Serum CGRP levels were negatively associated with SYNTAX scores in the CHD group (r=-0.522, p<0.001). The area under the curve of CGRP for identifying high SYNTAX scores (>22) was 0.772 [95% confidence interval (CI): 0.673-0.870, p<0.001], and for identifying high Gensini scores was 0.744 (95% CI: 0.646-0.842, p<0.001). A CGRP concentration of 25.05 pg/ml was selected as the cutoff point. A low CGRP level (<25.05 pg/ml) was an independent predictor of severe coronary stenosis, a SYNTAX score >22 [odds ratio (OR) =5.819, 95% CI: 2.240-15.116; p<0.001] and a high Gensini score (>64) (OR=4.943, 95% CI: 2.020-12.095; p<0.001). The low CGRP group had a higher incidence of major adverse cardiovascular events within two years (11.1 vs. 3.1%, p=0.031). Conclusion: In coronary atherosclerosis patients without acute myocardial injury, serum CGRP levels were negatively associated with the severity of coronary stenosis.

Anatomical Assessment vs. Pullback REsting full-cycle rAtio (RFR) Measurement for Evaluation of Focal and Diffuse CoronarY Disease: Rationale and Design of the “READY Register”

Background: The morphology and functional severity of coronary stenosis show poor correlation. However, in clinical practice, the visual assessment of the invasive coronary angiography is still the most common means for evaluating coronary disease. The fractional flow reserve (FFR), the coronary flow reserve (CFR), and the resting full-cycle ratio (RFR) are established indices to determine the hemodynamic significance of a coronary stenosis.Design/Methods: The READY register (NCT04857762) is a prospective, multicentre register of patients who underwent invasive intracoronary FFR and RFR measurement. The main aim of the registry is to compare the visual estimate of coronary lesions and the functional severity of the stenosis assessed by FFR, as well as the RFR pullback. Characterizations of the coronary vessel for predominantly focal, diffuse, or mixed type disease according to visual vs. RFR pullback determination will be compared. The secondary endpoint of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization at 1 year. These endpoints will be compared in patients with non-ischemic FFR in the subgroup of cases where the local pressure drop indicates a focal lesion according to the definition of ΔRFR &gt; 0.05 (for &lt;25 mm segment length) and in the subgroup without significant ΔRFR. In case of an FFR value above 0.80, an extended physiological analysis is planned to diagnose or exclude microvascular disease using the CFR/FFR index. This includes novel flow dynamic modeling for CFR calculation (CFRp−3D).Conclusion: The READY register will define the effect of RFR measurement on visual estimation-based clinical decision-making. It can identify a prognostic value of ΔRFR during RFR pullback, and it would also explore the frequency of microvascular disease in the patient population with FFR &gt; 0.80.Clinical Trial Registration:ClinicalTrials.gov (NCT04857762).

Relations of physical signs to genotype, lipid and inflammatory markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia

Background Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Methods LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed. Results Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04–10.72, p = 0.024). Conclusions Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.