Statement from the Asia Summit: Current state of arrhythmia care in Asia.

On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummit-22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life-threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region due to differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

2020 Asian Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region.

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

Initial experience with a leadless pacemaker (Micra™) implantation in a low volume center in South East Asia.

Aim: The Micra™ Transcatheter Pacing System is a leadless pacemaker that has been introduced recently. We share our experience in a low volume center and the use of right ventricular angiography (RVA) during implantation. Materials & methods: Patients underwent Micra implantation and RVA was performed to predetermine the implant site.Results: Nine patients underwent Micra implantation. The most common indication was atrial fibrillation with bradycardia. The device was implanted at apical-septum in seven and mid-septum in two. The procedure time ranged from 30 to 100 min and fluoroscopic time 4-18 min. Pacing parameters remained stable after 1-month follow-up. Conclusion: The Micra implantation technique can be easily learnt. RVA was helpful in selecting an appropriate site for the Micra implant.

Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase.

Angiotensin (ANG) II (AngII) and aldosterone contribute to the development of interstitial cardiac fibrosis. We investigated the potential role of a Nox2-containing NADPH oxidase in aldosterone-induced fibrosis and the involvement of this mechanism in AngII-induced effects. Nox2-/- mice were compared with matched wild-type controls (WT). In WT mice, subcutaneous (s.c.) AngII (1.1 mg/kg/day for 2 wk) significantly increased NADPH oxidase activity, interstitial fibrosis (11.5+/-1.0% vs. 7.2+/-0.7%; P<0.05), expression of fibronectin, procollagen I, and connective tissue growth factor mRNA, MMP-2 activity, and NF-kB activation. These effects were all inhibited in Nox2-/- hearts. The mineralocorticoid receptor antagonist spironolactone inhibited AngII-induced increases in NADPH oxidase activity and the increase in interstitial fibrosis. In a model of mineralocorticoid-dependent hypertension involving chronic aldosterone infusion (0.2 mg/kg/day) and a 1% Na Cl diet ("ALDO"), WT animals exhibited increased NADPH oxidase activity, pro-fibrotic gene expression, MMP-2 activity, NF-kB activation, and significant interstitial cardiac fibrosis (12.0+/-1.7% with ALDO vs. 6.3+/-0.3% without; P<0.05). These effects were inhibited in Nox2-/- ALDO mice (e.g., fibrosis 6.8+/-0.8% with ALDO vs. 5.8+/-1.0% without ALDO; P=NS). These results suggest that aldosterone-dependent activation of a Nox2-containing NADPH oxidase contributes to the profibrotic effect of AngII in the heart as well as the fibrosis seen in mineralocorticoid-dependent hypertension.

Involvement of the nicotinamide adenosine dinucleotide phosphate oxidase isoform Nox2 in cardiac contractile dysfunction occurring in response to pressure overload.

OBJECTIVES: This study sought to examine the role of Nox2 in the contractile dysfunction associated with pressure-overload left ventricular hypertrophy (LVH). BACKGROUND: Reactive oxygen species (ROS) production is implicated in the pathophysiology of LVH. The nicotinamide adenosine dinucleotide phosphate oxidase isoform, Nox2, is pivotally involved in angiotensin II-induced hypertrophy but is not essential for development of pressure-overload LVH. Its possible impact on contractile function is unknown. METHODS: The effects of aortic banding or sham surgery on cardiac contractile function and interstitial fibrosis were compared in adult Nox2-/- and matched wild-type (WT) mice. RESULTS: Banding induced similar increases in left ventricular (LV) mass in both groups. Banded Nox2-/- mice had better LV function than WT by echocardiography (e.g., fractional shortening 33.6 +/- 2.5% vs. 21.4 +/- 2.2%, p < 0.05). Comprehensive LV pressure-volume analyses also showed significant contractile dysfunction in banded WT compared with sham, whereas banded Nox2-/- mice had preserved function (e.g., maximum rate of rise of LV pressure: banded WT, 4,879 +/- 213; vs. banded Nox2-/-, 5,913 +/- 259 mm Hg/s; p < 0.05). Similar preservation of function was observed in isolated cardiomyocytes. The 24-h to 36-h treatment of banded WT mice with N-acetylcysteine resulted in recovery of contractile function. Cardiac interstitial fibrosis was significantly increased in banded WT but not Nox2-/- mice, together with greater increases in procollagen I and III mRNA expression. CONCLUSIONS: The Nox2 oxidase contributes to the development of cardiac contractile dysfunction and interstitial fibrosis during pressure overload, although it is not essential for development of morphologic hypertrophy per se. These data suggest divergent downstream effects of Nox2 on different components of the overall response to pressure overload.

Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning.

Reactive oxygen species (ROS)-mediated signaling is implicated in early ischemic preconditioning (PC). A NOX-2-containing NADPH oxidase is a recognized major source of ROS in cardiac myocytes, whose activity is augmented by preconditioning mimetics, such as angiotensin II. We hypothesized that this oxidase is an essential source of ROS in PC. Hearts from wild-type (WT) and NOX-2 knockout (KO) mice were Langendorff perfused and subjected to 35 min ischemia/reperfusion with or without preceding PC or drug treatment. Infarct size was measured by triphenyl tetrazolium chloride staining, and NADPH oxidase activity by lucigenin chemiluminescence. PC significantly attenuated infarct size in WT (26+/-2% vs. control, 38+/-2%, P<0.05) yet was ineffective in KO hearts (33+/-3% vs. control, 34+/-3%). Concomitantly, PC significantly increased NADPH oxidase activity in WT (+41+/-13%; P<0.05), but not in KO (-5+/-18%, P=NS). The ROS scavenger MPG (N-2-mercaptopropionyl glycine, 300 micromol/L) abrogated PC in WT (39+/-2% vs. control, 33+/-1%). CCPA (2-chloro N6 cyclopentyl adenosine, 200 nmol/L), a putative ROS-independent PC trigger, significantly attenuated infarct size in WT, MPG-treated WT and KO hearts (24+/-2, 23+/-1, and 20+/-3%, respectively, P<0.05). Furthermore, CCPA did not augment NADPH oxidase activity over control (+22+/-11%, P=NS). Inhibition of protein kinase C (PKC) with chelerythrine (CHE, 2 micromol/L) completely abrogated both PC (38+/-2% vs. CHE alone, 35+/-2%) and associated increases in oxidase activity (+3+/-10%, P=NS). PKC-dependent activation of a NOX-2-containing NADPH oxidase is pivotally involved in early ischemic PC. However, adenosine receptor activation can trigger a ROS and NOX-2 independent PC pathway.