Temporal Trends in Antithrombotic Therapy for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention From 2014 to 2022 in Japan.

Background: Recent revisions of clinical guidelines by the Japanese Circulation Society, American Heart Association/American College of Cardiology, and European Society of Cardiology updated the management of antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, the extent to which these guidelines have been implemented in real-world daily clinical practice is unclear. Methods and Results: We conducted surveys on the status of antithrombotic therapy for patients with AF undergoing PCI every 2 years from 2014 to 2022 in 14 cardiovascular centers in Japan. The primary use of drug-eluting stents increased from 10% in 2014 to 95-100% in 2018, and the use of direct oral anticoagulants increased from 15% in 2014 to 100% in 2018, in accordance with the revised practice guidelines. In patients with acute coronary syndrome, the duration of triple therapy within 1 month was approximately 10% until 2018, and increased to >70% from 2020. In patients with chronic coronary syndrome, the duration of triple therapy within 1 month was approximately 10% until 2016, and >75% from 2018. Since 2020, the most common timing of discontinuation of dual antiplatelet therapy to transition to anticoagulation monotherapy during the chronic phase of PCI has been 1 year after PCI. Conclusions: Japanese interventional cardiologists have updated their treatment strategies for patients with AF undergoing PCI according to revisions of clinical practice guidelines.

The Functional Severity Assessment of Coronary Stenosis Using Coronary Computed Tomography Angiography-Based Myocardial Mass at Risk and Minimal Lumen Diameter.

BACKGROUND: We investigated whether or not the addition of myocardial mass at risk (MMAR) to quantitative coronary angiography was useful for diagnosing functionally significant coronary stenosis in the daily practice. METHODS: We retrospectively enrolled 111 consecutive patients with 149 lesions who underwent clinically indicated coronary computed tomography angiography and subsequent elective coronary angiography with fractional flow reserve (FFR) measurement. MMAR was calculated using a workstation-based software program with ordinary thin slice images acquired for the computed tomography, and the minimal lumen diameter (MLD) and the diameter stenosis were measured with quantitative coronary angiography. RESULTS: The MLD and MMAR were significantly correlated with the FFR, and the MMAR-to-MLD ratio (MMAR/MLD) showed a good correlation. The area under the receiver operating characteristic curve (AUC) of MMAR/MLD for FFR ≤ 0.8 was 0.746, and the sensitivity, specificity, positive predictive value, and negative predictive value were 60%, 83%, 68%, and 77%, respectively, at a cut-off value of 29.5 ml/mm. The addition of MMAR/MLD to diameter stenosis thus made it possible to further discriminate lesions with FFR ≤ 0.8 (AUC = 0.750). For the proximal left coronary artery lesions, in particular, MMAR/MLD showed a better correlation with the FFR, and the AUC of MMAR/MLD for FFR ≤ 0.8 was 0.919 at a cut-off value of 31.7 ml/mm. CONCLUSIONS: The index of MMAR/MLD correlated well with the physiological severity of coronary stenosis and showed good accuracy for detecting functional significance. The MMAR/MLD might be a useful parameter to consider when deciding the indication for revascularization.

Coronary Artery Disease Screening With Carotid Ultrasound Examination by a Primary Care Physician.

BACKGROUND: In this study, we investigated the feasibility of primary care physicians using carotid ultrasound to perform coronary artery disease screening in asymptomatic patients with multiple coronary risk factors. METHODS: We retrospectively collected the data of 135 consecutive asymptomatic patients (mean age: 68.5 ± 8.4 years; male, 75%) who were referred to our institution due to abnormal findings on a carotid ultrasound performed by a primary care physician and who underwent coronary computed tomography angiography. RESULTS: The mean number of risk factors was 4.1 ± 1.2 and the mean intima-media thickness was 2.00 ± 0.63 mm. Mild (≤ 50%), moderate (51-75%), and severe (> 76%) coronary stenosis was observed in 54 (40%), 27 (20%), and 25 patients (19%), respectively, while no plaque was found in 24 patients (18%), and five patients (4%) could not be evaluated due to calcification. Consequently, coronary angiography was performed in 56 (41%) patients and coronary intervention was required in 31 patients (23%). A multivariate logistic regression analysis demonstrated that the ratio of low-density lipoprotein cholesterol levels to high-density lipoprotein cholesterol levels, the use of calcium channel blockers and the value of the diastolic blood pressure were related to > 50% coronary stenosis. CONCLUSIONS: The use of carotid ultrasound in the coronary artery disease screening by primary care physicians resulted in a high prevalence of coronary artery disease and high probabilities of coronary angiography and revascularization, and thus it is considered to be a useful and feasible strategy for the screening of asymptomatic patients.

Blackout during meals: A case report of swallow syncope due to sinus arrest.

A 79-year-old male, with a history of percutaneous coronary intervention (PCI), was referred to our cardiovascular department for a detailed examination of blackout caused by sinus arrest only during meals. Ultrasound echocardiography showed normal cardiac contraction with no asynergy, irrespective of the remaining stenotic coronary lesion. An electrophysiological study revealed deteriorated atrioventricular nodal conduction at a Wenckebach point of 70 beats per minute. However, sinus node function was normal as demonstrated by a sinus node recovery time of 1369 ms. Coronary angiography showed triple-vessel disease including the remaining stenotic coronary lesion, and a PCI was performed on the right coronary artery. Nevertheless, sinus arrest during meals was unchanged. Swallow syncope was partially improved by dietary modification; however, pacemaker implantation (PMI) was performed eventually, and the patient became asymptomatic after PMI. .

Resolution of a left ventricular thrombus by the thrombolytic action of dabigatran.

A 77-year-old man was referred to our cardiovascular department for detailed examination after abnormal electrocardiography findings were obtained during a preoperative cataract surgery workup. Ultrasound echocardiography (UCG) and computed tomography (CT) revealed evidence of previous myocardial infarction with anteroseptal akinesis and a left ventricular (LV) thrombus (14 × 12 mm). Dabigatran (220 mg/day) was prescribed as an outpatient treatment, and the disappearance of the LV thrombus was confirmed by UCG and CT 27 days after dabigatran initiation. No thromboembolism occurred between treatment initiation and thrombus resolution. Our results indicate that dabigatran has thrombolytic action on an acute pre-existing intracardiac thrombus.

Ventricular pacing inhibition by oversensing due to diaphragmatic myopotential during deep inspiration.

An 80-year-old man, who had dilated cardiomyopathy with right ventricular (RV) dilatation, underwent implantable cardioverter defibrillator (ICD) implantation for advanced atrioventricular block and primary prevention of sudden cardiac death. Tined and screw-in leads were placed on the right atrial appendage and RV apex, respectively. Ventricular pacing inhibition was detected after surgery due to oversensing by diaphragmatic myopotential occurring only during deep inspiration. We performed re-surgery and switched the screw-in lead for a tined lead. The diaphragmatic myopotential decreased, thereby improving oversensing by diaphragmatic myopotential and ventricular pacing inhibition. It might be beneficial to use a tined lead when placing the ventricular lead at the RV apex for implantation of a pacemaker or ICD if oversensing of diaphragmatic myopotential is observed using a screw-in lead. .

High salt intake enhances blood pressure increase during development of hypertension via oxidative stress in rostral ventrolateral medulla of spontaneously hypertensive rats.

High salt intake increases blood pressure (BP) in spontaneously hypertensive rats (SHR), and central neural mechanisms are suggested to be involved. Increased generation of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) contributes to the neural mechanism of hypertension in SHR. We sought to examine whether high salt intake increases hypertension in SHR and whether the increased ROS in the RVLM contributes to this mechanism. Male SHR and Wistar-Kyoto rats (WKY) (6 weeks old) were fed a high-salt diet (8%: HS-S; HS-W) or a regular-salt diet (0.5%: RS-S; RS-W) for 6 weeks. Systolic BP was significantly higher in HS-S than in RS-S at 12 weeks of age (244+/-5 vs. 187+/-7 mmHg, n=8; p<0.05). Urinary norepinephrine excretion was significantly higher in HS-S than in RS-S. Thiobarbituric acid-reactive substances levels in the RVLM were significantly higher in HS-S than in RS-S (9.9+/-0.5 vs. 8.1+/-0.6 mumol/g wet wt, n=5; p<0.05). Microinjection of tempol or valsartan into the RVLM induced significantly greater BP reduction in HS-S than in RS-S. The increase in angiotensin II type 1 receptor (AT(1)R) expression and the increase in reduced nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase activity in the RVLM were significantly greater in HS-S than in RS-S. These findings indicate that high salt intake exacerbates BP elevation and sympathetic nervous system activity during the development of hypertension in SHR. These responses are mediated by increased ROS generation that is probably due to upregulation of AT(1)R/NAD(P)H oxidase in the RVLM. (Hypertens Res 2008; 31: 2075-2083).

Azelnidipine decreases sympathetic nerve activity via antioxidant effect in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats.

The long-acting dihydropyridine calcium channel blocker, azelnidipine, is suggested to inhibit sympathetic nerve activity. We previously demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM) activates sympathetic nerve activity. The aim of the present study was to determine whether oral administration of azelnidipine inhibits sympathetic nerve activity and if so to determine whether the effect is mediated by antioxidant effect in the RVLM. Azelnidipine, hydralazine, or vehicle was orally administered for 28 days to stroke-prone spontaneously hypertensive rats. Reductions in systolic blood pressure were similar in azelnidipine and hydralazine groups. Heart rate was significantly higher in the hydralazine group than in the control, but not altered in the azelnidipine group. Urinary norepinephrine excretion as an indicator of sympathetic nerve activity was significantly lower in the azelnidipine group, whereas it was significantly higher in the hydralazine group than in the control. Levels of thiobarbituric acid-reactive substances and nicotinamide adenine dinucleotide phosphate oxidase activity were significantly lower in the azelnidipine group than in control. Superoxide dismutase activity was significantly increased in the azelnidipine group more than in the control. These results suggest that azelnidipine decreases an indicator of sympathetic nerve activity by antioxidant effect mediated through inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity and activation of superoxide dismutase in the RVLM of stroke-prone spontaneously hypertensive rats.

Mitochondria-derived reactive oxygen species mediate sympathoexcitation induced by angiotensin II in the rostral ventrolateral medulla.

OBJECTIVES: Reactive oxygen species (ROS) in the central nervous system are thought to contribute to sympathoexcitation in cardiovascular diseases such as hypertension and heart failure. Nicotinamide adenine dinucleotide phosphate oxidase is a major source of ROS in the central nervous system, which acts as a key mediator (mediators) of angiotensin II (AngII). It is not clear, however, whether mitochondria-derived ROS in the central nervous system also participate in sympathoexcitation. METHODS: In an in-vivo study, we investigated whether the AngII-elicited pressor response in the rostral ventrolateral medulla, which controls sympathetic nerve activity, is attenuated by adenovirus-mediated gene transfer of a mitochondria-derived antioxidant (Mn-SOD). In an in-vitro study, using differentiated PC-12 cells with characteristics similar to those of sympathetic neurons, we examined whether AngII increases mitochondrial ROS production. RESULTS: Overexpression of Mn-SOD attenuated the AngII-induced pressor response and also suppressed AngII-induced ROS production, as evaluated by microdialysis in the rostral ventrolateral medulla. Using reduced MitoTracker red, we showed that AngII increased mitochondrial ROS production in differentiated PC-12 cells in vitro. Overexpression of Mn-SOD and rotenone, a mitochondrial respiratory complex I inhibitor, suppressed AngII-induced ROS production. Depletion of extracellular Ca2+ with ethylene glycol bis-N,N,N',N'-tetraacetate (EGTA) and administration of p-trifluoromethoxycarbonylcyanide phenylhydrazone, which prevents further Ca2+ uptake into the mitochondria, blocked AngII-elicited mitochondrial ROS production. CONCLUSION: These results indicate that AngII increases the intracellular Ca2+ concentration and that the increase in mitochondrial Ca2+ uptake leads to mitochondrial ROS production.

Inhibition of Rac1-derived reactive oxygen species in nucleus tractus solitarius decreases blood pressure and heart rate in stroke-prone spontaneously hypertensive rats.

Reactive oxygen species (ROS) in the brain are thought to contribute to the neuropathogenesis of hypertension by enhancing sympathetic nervous system activity. The nucleus tractus solitarius (NTS), which receives afferent input from baroreceptors, has an important role in cardiovascular regulation. reduced nicotinamide-adenine dinucleotide phosphate oxidase is thought to be a major source of ROS in the NTS. Rac1 is a small G protein and a key component of reduced nicotinamide-adenine dinucleotide phosphate oxidase. The role of Rac1-derived ROS in the NTS in cardiovascular regulation of hypertension is unknown. Therefore, we examined whether inhibition of Rac1 in the NTS decreases ROS generation, thereby reducing blood pressure in stroke-prone spontaneously hypertensive rats (SHRSPs). The basal Rac1 activity level in the NTS was greater in SHRSPs than in Wistar-Kyoto rats. Inhibition of Rac1, induced by transfecting adenovirus vectors encoding dominant-negative Rac1 into the NTS, decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSPs but not in Wistar-Kyoto rats. Inhibition of Rac1 also reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and ROS generation. In addition, Cu/Zn-superoxide dismutase activity in the NTS of SHRSPs was decreased compared with that of Wistar-Kyoto rats, despite the increased ROS generation. Overexpression of Cu/Zn-superoxide dismutase in the NTS decreased blood pressure and heart rate in SHRSPs. These results indicate that the activation of Rac1 in the NTS generates ROS via reduced nicotinamide-adenine dinucleotide phosphate oxidase in SHRSPs, and this mechanism might be important for the neuropathogenesis of hypertension in SHRSPs.