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Abstract The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient −0.34, 95% CI −0.50 to −0.18, p

Abstract Aims Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR‐2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR‐2 (sVEGFR‐2) levels is associated with poor prognosis in patients with chronic heart failure (HF). Methods and results We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR‐2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all‐cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR‐2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (

Abstract Purpose Phrenic nerve injury (PNI) is one of the important complications during cryoballoon (CB) ablation. Recording diaphragmatic compound motor action potentials (CMAPs) during CB ablation can predict PNI. CMAP monitoring may be inaccurate when CMAP amplitudes are low. We examined the effect of positioning an electrocardiography (ECG) electrode at the dorsal side. Methods We retrospectively analyzed the cases of 197 consecutive patients who underwent CB ablation for pulmonary vein isolation (PVI) (April 2016 to December 2018) at our institution. CMAP amplitudes were monitored using two recording methods just before cryoapplication. (a) Conventional method: right‐arm ECG electrode positioned 5 cm above the xiphoid on the ventral side; left‐arm ECG electrode positioned along the costal margin. (b) Our original method: right‐arm electrode positioned 5 cm above the xiphoid on the dorsal side; left‐arm electrode positioned along the costal margin. Results The CMAP amplitude during right phrenic nerve pacing was significantly higher at the dorsal side than the ventral side (0.80 ± 0.31 mV vs 0.66 ± 0.29 mV, P

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high‐risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms‐like tyrosine kinase‐1 (sFlt‐1), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin‐I (hs‐cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3‐point MACE (3P‐MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all‐cause death, cardiovascular death, and 5P‐MACE defined as a composite of 3P‐MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt‐1, NT‐proBNP, and hs‐cTnI, but not other biomarkers, were significantly associated with 3P‐MACE, all‐cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT‐proBNP and hs‐cTnI. NT‐proBNP and hs‐cTnI were also significantly associated with 5P‐MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT‐proBNP and hs‐cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT‐proBNP and hs‐cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Background Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Background: Hypertension, diabetes, dyslipidemia and smoking are established coronary risk factors for coronary heart disease in the general population. However, in Japanese patients with acute myocardial infarction (AMI), the impact of the number of coronary risk factors on in-hospital morality remains unclear. Methods: The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide real-world database. We examined the association between the number of coronary risk factors and in-hospital mortality. Results: Data were obtained from total of 20462 AMI patients (mean age, 68.8 ± 13.3 years old; 15281 men, 5181 women). The prevalence of hypertension increased with advancing age, while the prevalence of smoking decreased with advancing age. The prevalence of diabetes and dyslipidemia were highest in middle age. A majority (76.9%) of the patients with AMI had at least 1 of these coronary risk factors. Overall, the number of coronary risk factor was relatively less in older subjects and women under 50 years old. Crude in-hospital mortality rates were 10.7%, 10.5%, 7.2%, 5.0% and 4.5% with 0, 1, 2, 3 and 4 risk factors, respectively. After adjusting for age and sex, there was an inverse association between the number of coronary risk factors and the in-hospital mortality (adjusted odds ratio [1.68; 95% confidence interval, 1.20–2.35] among individuals with 0 vs. 4 risk factors). Conclusion: In the present study of Japanese patients with AMI, who received modern medical treatment, in-hospital mortality was inversely related to the number of coronary risk factors. To investigate the underlying reasons for these findings, further studies are needed.

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor‐C (VEGF‐C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF‐C. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF‐C levels were significantly and inversely associated with all‐cause death (hazard ratio for 1‐SD increase, 0.69; 95% confidence interval, 0.60–0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53–0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72–1.01). Even after incorporation of N‐terminal pro‐brain natriuretic peptide, contemporary sensitive cardiac troponin‐I, and high‐sensitivity C‐reactive protein into a model with established risk factors, the addition of VEGF‐C levels further improved the prediction of all‐cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF‐C value may independently predict all‐cause mortality.

We report a case of clonic-tonic seizures diagnosed using an implantable loop recorder, a device for detecting cardiac arrhythmias. A 65-year-old man was referred to our hospital for loss of consciousness with myotonic jerks during sleep. He had experienced several similar episodes. No family history of sudden death was evident, and no structural heart disease was present. Coronary angiography with intracoronary acetylcholine (ACh) showed neither organic stenosis nor vasospastic angina. Ventricular tachyarrhythmias were not induced by programmed electrical stimuli. Sleep electroencephalography, brain magnetic resonance imaging and magnetic resonance angiography revealed no specific findings. We implanted a loop recorder to monitor rhythm abnormalities. One month later, an attack occurred at night. His wife recognized the episode and activated the implantable loop recorder. No arrhythmia was recorded, but myopotentials characteristic of tonic-clonic seizures were detected.