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

Asian Pacific Society of Cardiology Consensus Recommendations on the Use of MitraClip for Mitral Regurgitation

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted ‘agree’ or ‘neutral’. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation

Impact of COVID-19 Pandemic on TAVR Activity: A Worldwide Registry

Background: The COVID-19 pandemic had a considerable impact on the provision of structural heart intervention worldwide. Our objectives were: 1) to assess the impact of the COVID-19 pandemic on transcatheter aortic valve replacement (TAVR) activity globally; and 2) to determine the differences in the impact according to geographic region and the demographic, development, and economic status of diverse international health care systems. Methods: We developed a multinational registry of global TAVR activity and invited individual TAVR sites to submit TAVR implant data before and during the COVID-19 pandemic. Specifically, the number of TAVR procedures performed monthly from January 2019 to December 2021 was collected. The adaptive measures to maintain TAVR activity by each site were recorded, as was a variety of indices relating to type of health care system and national economic indices. The primary subject of interest was the impact on TAVR activity during each of the pandemic waves (2020 and 2021) compared with the same period pre–COVID-19 (2019). Results: Data were received from 130 centers from 61 countries, with 14 subcontinents and 5 continents participating in the study. Overall, TAVR activity increased by 16.7% (2,337 procedures) between 2018 and 2019 (ie, before the pandemic), but between 2019 and 2020 (ie, first year of the pandemic), there was no significant growth (–0.1%; –10 procedures). In contrast, activity again increased by 18.9% (3,085 procedures) between 2020 and 2021 (ie, second year of the pandemic). During the first pandemic wave, there was a reduction of 18.9% (945 procedures) in TAVR activity among participating sites, while during the second and third waves, there was an increase of 6.7% (489 procedures) and 15.9% (1,042 procedures), respectively. Further analysis and results of this study are ongoing and will be available at the time of the congress. Conclusion: The COVID-19 pandemic initially led to a reduction in the number of patients undergoing TAVR worldwide, although health care systems subsequently adapted, and the number of TAVR recipients continued to grow in subsequent COVID-19 pandemic waves. Categories: STRUCTURAL: Valvular Disease: Aorti

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI : Results of the ISACS-STEMI COVID-19 Registry

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March–June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825–0.861, p < 0.0001). We found a significant agerelated reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24–1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05–1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry

Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (= 75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic