According to a patient-level pooled analysis of the DAPA-HF and DELIVER trials, the efficacy and safety of dapagliflozin, a SGLT2 inhibitor, were consistent across global regions despite differences in patient characteristics, background treatment and event rates. Toru Kondo, MD, PhD, et al., found that the benefit of dapagliflozin on the primary outcome, defined as the composite of worsening heart failure (HF) or cardiovascular death, did not vary by region: Europe, 0.85 (95% CI, 0.75-0.96); North America, 0.75 (95% CI, 0.61-0.93); South America, 0.72 (95% CI, 0.58-0.89); and Asia, 0.74 (95% CI, 0.61-0.91) (p=0.40). In an accompanying editorial comment, Javed Butler, MBBS, FACC; Muhammad Shahzeb Khan, MD, MSc; and Gregg C. Fonarow, MD, FACC, add: "The key takeaway message from this study should be that SGLT2 inhibitors specifically, and the overall treatment of HF, need to be applied equally across different geographic regions, and our focus should be on implementation of these therapies globally."

A comprehensive meta-analysis of more than 40 studies conducted by Pedro E. P. Carvalho, et al., sought to determine the optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with nonvalvular atrial fibrillation. Use of direct oral anticoagulants (DOACs), vitamin-K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, and VKA plus SAPT was compared with no antithrombotic therapy. Of the 12,451 patients analyzed, DOACs exhibited the highest likelihood of lower thromboembolic events and major bleeding. In addition, DAPT was associated with a lower rate of thromboembolic events compared with SAPT.

Paolo Bima, MD, et al., investigated the prevalence of acute myocardial infarction (AMI) in cancer patients presenting to the emergency department (ED) with chest pain along with the efficacy of high-sensitivity cardiac troponins and diagnostic algorithms in this patient group. Among 8,267 patients included in the study, 711 (7.6%) had cancer. Results showed that cancer patients had a higher prevalence of AMI as the cause of chest pain (26.8% with cancer vs. 21.1% without cancer; p<0.001). Researchers also found that cancer was associated with increased length of ED stay and hospitalization rates, and that the diagnostic accuracy of high-sensitivity troponin for NSTEMI as well as the efficacy of European Society of Cardiology 0/1-h-hs-cTnT and I algorithms were reduced.

In a study of the nature of nitric oxide bioactivity in red blood cells (RBCs), Tong Jiao, MD, PhD, et al., identified a pathway in which stimulation of soluble guanylyl cyclase (sGC) induces release of a cardioprotective factor – exporting cyclic guanosine monophosphate that then activates cardiac protein kinase G – which protects from myocardial ischemia-reperfusion injury. This discovery may present a novel therapeutic target for prevention of cardiac injury in patients with type 2 diabetes. Researchers acknowledge several study limitations, including that "the effect of RBCs was evaluated in an isolated rat heart model ex vivo, and therefore it cannot be determined from these data the extent to which sGC stimulation in RBCs may contribute to cardioprotection in vivo in humans."

Through an assessment of the prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population, Emma F. Magavern, MD, MSc, et al., found that of 44,396 participants in the Genes and Health cohort of British Bangladeshi and Pakistani ancestry, 13% were considered poor metabolizers, carrying two CYP2C19 loss-of-function alleles, which is much higher than found in previously studied European (2.4%) and Central/South Asian (8.2%) groups. Researchers note that 69% of the cohort who were diagnosed with an AMI were prescribed clopidogrel, and those considered poor metabolizers had a greater likelihood of recurrent myocardial infarction (MI) (OR, 3.1; p=0.019). In a related editorial comment, Rolf P. Kreutz, MD, FACC, says the study "adds to the growing evidence that CYP2C19 poor or intermediate metabolizers treated with clopidogrel are at increased risk for recurrent [MI] and supports the use of pharmacogenomic testing for clopidogrel resistance in at risk patient populations."

Presenting results from the SWAP-6 study, Francesco Franchi, MD, et al., randomized 77 patients undergoing PCI to one of three groups – prasugrel only at start of PCI, cangrelor plus prasugrel concomitantly at start of PCI, or cangrelor at start of PCI plus prasugrel at end of infusion – to determine if a drug-drug interaction exists when transitioning from intravenous P2Y12 inhibition with cangrelor to oral P2Y12 inhibition with prasugrel. Results found that "concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a [drug-drug interaction]."

When compared with downtime and current selection criteria, Robert Aldous, BSc, MRCP, et al., found the MIRACLE₂ Score had superior prediction of outcome after out-of-hospital cardiac arrest than downtime and higher discrimination of poor outcome than current randomized control trial recruitment criteria. The study included 1,259 patients from the European Cardiac Arrest Registry, and the primary outcome was poor neurological outcome on hospital discharge, defined as Cerebral Performance Category 3-5. The authors note their findings have several clinical implications in both determining appropriate selection of out-of-hospital cardiac arrest patients for invasive therapies as well as future randomized controlled trials.

A study evaluating stressed blood volume in patients with severe tricuspid regurgitation (TR) and its implications for transcatheter tricuspid edge-to-edge repair (TEER). Investigators found that estimated stressed blood volume, calculated from hemodynamic variables fit to a comprehensive cardiovascular model, was associated with obesity, renal and liver dysfunction, more severe HF, attenuated reduction of venous congestion after TEER and adverse clinical outcomes. "These findings provide new insights into the potential mechanistic links between excessive blood volume and abnormalities in venous capacitance/compliance, obesity, hepatic/renal function as well as RV-PA coupling and TR-associated right-sided HF," write Karl-Philipp Rommel, MD, et al. "The present data also suggest that therapies targeting [stressed blood volume] may be promising to reduce residual risk in TR patients undergoing TEER."