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with a long life expectancy, it will become increasingly important to understand the impact of permanent pacemaker implantation after TAVR.

This study sought to investigate the impact of computed tomography (CT)-based area and perimeter oversizing on the incidence of paravalvular regurgitation (PVR) and valve hemodynamics in patients treated with the SAPIEN 3 transcatheter heart valve (THV).

The incremental value of considering annular perimeter or left ventricular outflow tract measurements and the impact of THV oversizing on valve hemodynamics are not well defined.

The PARTNER 3 (Placement of Aortic Transcatheter Valves 3) trial included 495 low-surgical-risk patients with severe aortic stenosis who underwent THV implantation. THV sizing was based on annular area assessed by CT. Area- and perimeter-based oversizing was determined using systolic annular CT dimensions and nominal dimensions of the implanted THV. PVR, effective orifice area, and mean gradient were assessed on 30-day transthoracic echocardiography.

Of 485 patients with available CT and echocardiography data, mean oversizing was 7.9 ± 8.7% for the annulus area and 2.1 ± 4.1% to both the annular area and perimeter reduced PVR and optimized THV hemodynamics.

In low-surgical-risk patients, a low incidence of ≥moderate PVR was observed, including patients with minimal THV oversizing. The degree of prosthesis oversizing had the greatest impact on reducing mild PVR and incidence of post-dilatation, without impacting valve hemodynamics. In selected patients with annular dimensions in between 2 valve sizes, the larger THV device oversized to both the annular area and perimeter reduced PVR and optimized THV hemodynamics.

The aim of this study was to compare the feasibility, safety, and clinical outcomes of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) stenosis.

At present, limited observational data exist supporting TAVR in the context of bicuspid anatomy.

Primary endpoints were 1-year survival and device success. Secondary endpoints included moderate to severe paravalvular leak (PVL) and a composite endpoint of periprocedural complications; incidence rates of individual procedural endpoints were also explored individually.

In the main analysis, 17 studies and 181,433 patients undergoing TAVR were included, of whom 6,669 (0.27%) had BAV. A secondary analysis of 7,071 matched subjects with similar baseline characteristics was also performed. Device success and 1-year survival rates were similar between subjects with BAV and those with TAV (97% vs 94% [P=0.55] and 91.3% vs 90.8% [P=0.22], respectively). In patients with BAV, a trend toward a higher risk for periprocedural complications was observed in our main analysis (risk ratio [RR] 1.12; 95% CI 0.99-1.27; P=0.07) but not in the matched population secondary analysis (RR 1.00; 95%CI 0.81-1.24; P=0.99). The risk for moderate to severe PVL was higher in subjects with BAV (RR 1.42; 95%CI 1.29-1.58; P< 0.0001) as well as the incidence of cerebral ischemic events (2.4% vs 1.6%; P=0.015) and of annular rupture (0.3% vs 0.02%; P=0.014) in matched subjects.

TAVR is a feasible option among selected patients with BAV anatomy, but the higher rates of moderate to severe PVL, annular rupture, and cerebral ischemic events observed in the BAV group warrant caution and further evidence.

TAVR is a feasible option among selected patients with BAV anatomy, but the higher rates of moderate to severe PVL, annular rupture, and cerebral ischemic events observed in the BAV group warrant caution and further evidence.

The aim of this retrospective analysis was to categorize patients with severe aortic stenosis (AS) according to clinical presentation by applying unsupervised machine learning.

Patients with severe AS present with heterogeneous clinical phenotypes, depending on disease progression and comorbidities.

Unsupervised agglomerative clustering was applied to preprocedural data from echocardiography and right heart catheterization from 366 consecutively enrolled patients undergoing transcatheter aortic valve replacement for severe AS.

Cluster analysis revealed 4 distinct phenotypes. Patients in cluster 1 (n=164 [44.8%]), serving as a reference, presented with regular cardiac function and without pulmonary hypertension (PH). Accordingly, estimated 2-year survival was 90.6% (95% CI 85.8%-95.6%). Clusters 2 (n=66 [18.0%]) and 4 (n=91 [24.9%]) both comprised patients with postcapillary PH. Yet patients in cluster 2 with preserved left and right ventricular structure and function showed a similar survival as thoseresentations as observed in patients with severe AS. Importantly, structural alterations in left and right heart morphology, possibly due to genetic predisposition, constitute an equally sensitive indicator of poor prognosis compared with high-grade PH.

The aim of this study was to examine the applicability of pivotal transcatheter aortic valve replacement (TAVR) trials to the real-world population of Medicare patients undergoing TAVR.

It is unclear whether randomized controlled trial results of novel cardiovascular devices apply to patients encountered in clinical practice.

Characteristics of patients enrolled in the U.S. CoreValve pivotal trials were compared with those of the population of Medicare beneficiaries who underwent TAVR in U.S. clinical practice between November 2, 2011, and December 31, 2017. Inverse probability weighting was used to reweight the trial cohort on the basis of Medicare patient characteristics, and a "real-world" treatment effect was estimated.

A total of 2,026 patients underwent TAVR in the U.S. CoreValve pivotal trials, and 135,112 patients underwent TAVR in the Medicare cohort. Trial patients were mostly similar to real-world patients at baseline, though trial patients were more likely to have hypertension (50% vs 39%)d trial treatment effect, suggesting that the absolute benefit of TAVR in clinical trials is similar to the benefit of TAVR in the U.S. Linsitinib real-world setting.Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist, with up to two thirds of patients with AS having significant CAD. Given the challenges when both disease states are present, these patients require a tailored approach diagnostically and therapeutically. In this review the authors address the impact of AS and aortic valve replacement (AVR) on coronary hemodynamic status and discuss the assessment of CAD and the role of revascularization in patients with concomitant AS and CAD. Remodeling in AS increases the susceptibility of myocardial ischemia, which can be compounded by concomitant CAD. AVR can improve coronary hemodynamic status and reduce ischemia. Assessment of the significance of coexisting CAD can be done using noninvasive and invasive metrics. Revascularization in patients undergoing AVR can benefit certain patients in whom CAD is either prognostically or symptomatically important. Identifying this cohort of patients is challenging and as yet incomplete. Patients with dual pathology present a diagnostic and therapeutic challenge; both AS and CAD affect coronary hemodynamic status, they provoke similar symptoms, and their respective treatments can have an impact on both diseases. Decisions regarding coronary revascularization should be based on understanding this complex relationship, using appropriate coronary assessment and consensus within a multidisciplinary team.Within the overlapping geographical ranges of P. knowlesi monkey hosts and vectors in Southeast Asia, an estimated 1.5 billion people are considered at risk of infection. P. knowlesi can cause severe disease and death, the latter associated with delayed treatment occurring from misdiagnosis. Although microscopy is a sufficiently sensitive first-line tool for P. knowlesi detection for most low-level symptomatic infections, misdiagnosis as other Plasmodium species is common, and the majority of asymptomatic infections remain undetected. Current point-of-care rapid diagnostic tests demonstrate insufficient sensitivity and poor specificity for differentiating P. knowlesi from other Plasmodium species. Molecular tools including nested, real-time, and single-step PCR, and loop-mediated isothermal amplification (LAMP), are sensitive for P. knowlesi detection. However, higher cost and inability to provide the timely point-of-care diagnosis needed to guide appropriate clinical management has limited their routine use in most endemic clinical settings. P. knowlesi is likely underdiagnosed across the region, and improved diagnostic and surveillance tools are required. Reference laboratory molecular testing of malaria cases for both zoonotic and non-zoonotic Plasmodium species needs to be more widely implemented by National Malaria Control Programs across Southeast Asia to accurately identify the burden of zoonotic malaria and more precisely monitor the success of human-only malaria elimination programs. The implementation of specific serological tools for P. knowlesi would assist in determining the prevalence and distribution of asymptomatic and submicroscopic infections, the absence of transmission in certain areas, and associations with underlying land use change for future spatially targeted interventions.The zoonotic parasite Plasmodium knowlesi has emerged as an important cause of human malaria in parts of Southeast Asia. The parasite is indistinguishable by microscopy from the more benign P. malariae, but can result in high parasitaemias with multiorgan failure, and deaths have been reported. Recognition of severe knowlesi malaria, and prompt initiation of effective therapy is therefore essential to prevent adverse outcomes. Here we review all studies reporting treatment of uncomplicated and severe knowlesi malaria. We report that although chloroquine is effective for the treatment of uncomplicated knowlesi malaria, artemisinin combination treatment is associated with faster parasite clearance times and lower rates of anaemia during follow-up, and should be considered the treatment of choice, particularly given the risk of administering chloroquine to drug-resistant P. vivax or P. falciparum misdiagnosed as P. knowlesi malaria in co-endemic areas. For severe knowlesi malaria, intravenous artesunate has been shown to be highly effective and associated with reduced case-fatality rates, and should be commenced without delay. Regular paracetamol may also be considered for patients with severe knowlesi malaria or for those with acute kidney injury, to attenuate the renal damage resulting from haemolysis-induced lipid peroxidation.Within the past two decades, incidence of human cases of the zoonotic malaria Plasmodium knowlesi has increased markedly. P. knowlesi is now the most common cause of human malaria in Malaysia and threatens to undermine malaria control programmes across Southeast Asia. The emergence of zoonotic malaria corresponds to a period of rapid deforestation within this region. These environmental changes impact the distribution and behaviour of the simian hosts, mosquito vector species and human populations, creating new opportunities for P. knowlesi transmission. Here, we review how landscape changes can drive zoonotic disease emergence, examine the extent and causes of these changes across Southeast and identify how these mechanisms may be impacting P. knowlesi dynamics. We review the current spatial epidemiology of reported P. knowlesi infections in people and assess how these demographic and environmental changes may lead to changes in transmission patterns. Finally, we identify opportunities to improve P. knowlesi surveillance and develop targeted ecological interventions within these landscapes.

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