European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Association between ablation technology and asymptomatic cerebral injury following atrial fibrillation ablation.

BACKGROUND: Asymptomatic cerebral injury (ACI) detected by diffusion-weighted magnetic resonance imaging (MRI) following atrial fibrillation (AF) ablation has been reported recently. The purpose of this study was to provide an overview of the incidence of ACI detected by MRI following AF ablation and to explore the association between ablation technology and ACI by systematically reviewing published trials. METHODS AND RESULTS: PubMed, Web of Science, and the Cochrane Library Databases were systematically searched for studies exploring ACI detected by MRI following AF ablation. Incidence of ACI, odds ratios, and 95% confidence intervals (CIs) were pooled. We identified 21 eligible studies. The combined ACI incidence across all studies was 15.9% (95% CI: 0.124-0.202). We also did a subgroup analysis stratified by different technologies. The incidence of ACI stratified by ablation technology was 13.0%, 27.6%, 12.5%, 17.3%, and 32.6% of the irrigated radiofrequency (RF), multielectrode-phased RF pulmonary vein ablation catheter (PVAC), cryoballoon, laser balloon, and nMARQTM groups, respectively. CONCLUSIONS: The incidence of ACI following AF ablation with PVAC was higher than with other technologies. Uninterrupted oral anticoagulant (OAC) during the procedure could lower the incidence of ACI. It seems prudent not to interrupt OACs during the procedure. In addition, intraprocedural activated clotting time was associated with ACI. Different MRI diagnostic criteria for ACI also influenced the results. To facilitate the future research, a generally accepted definition for silent cerebrovascular ischemia suitable to different kinds of MRI is needed.

Prognostic value of plasma pentraxin-3 levels in patients with stable coronary artery disease after drug-eluting stent implantation.

Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP). Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD) after drug eluting stent (DES) implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI) and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1-5) for major adverse cardiovascular events (MACEs). We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL) had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP) were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.

Real-World Effectiveness of Ivabradine in Chinese Patients with Chronic Heart Failure: Interim Analysis of the POSITIVE Study.

BACKGROUND: Ivabradine improves cardiac function and clinical outcomes in chronic heart failure (HF) by reducing heart rate (HR), but there is a lack of real-world data on its effectiveness and safety in Chinese patients. METHODS: We designed a prospective, multicenter, observational study of Chinese adults with HF and left ventricular systolic dysfunction, resting HR ≥ 75 beats per minute (bpm), and an indication for ivabradine treatment. An interim analysis was performed using a cut-off date of 31 October 2019. The primary outcome was change in HR at 6 months after the initiation of ivabradine. Secondary endpoints included change in New York Heart Association (NYHA) functional class; quality of life (QoL), measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ); and adverse events (AEs). RESULTS: Overall, 655 subjects were included in the interim analysis. Mean reduction in HR from baseline was 13.2 (95% confidence interval [CI] 11.2-15.2) bpm at Month 1, and 14.5 (95% CI 11.8-17.2) bpm at Month 6 (p < 0.001 for both changes). NYHA functional class and KCCQ scores improved significantly over time (p < 0.001 for all comparisons with baseline), indicating amelioration of symptoms and better QoL, respectively. Forty-four subjects (6.7%) reported a total of 60 ivabradine-related AEs, most frequently phosphenes and bradycardia (both n = 6, 0.9%). CONCLUSION: Treatment with ivabradine for 6 months effectively reduced HR and improved functional class and QoL in Chinese patients with chronic HF. Treatment was well tolerated. CLINICAL TRIAL REGISTRATION: ISRCTN11703380; registered on 8 November 2016.

Dendritic cells derived exosomes migration to spleen and induction of inflammation are regulated by CCR7.

Mature dendritic cells (DCs) home to secondary lymphoid organs through CC chemokine receptor 7 (CCR7). Exosomes derived from DCs (DC-exos) are reported to migrate to spleen and induce inflammation in vivo. In this study, we demonstrated that mature bone marrow DC-exos can activate immature DC and T cells in vitro. Then we intravenously injected DC-exos into C57BL/6 mice, observing that mature DC-exos accumulated more in spleen than immature DC-exos. These DC-exos in spleen could be uptaken by splenetic DCs and T cells and induce an inflammatory response. We further showed that the increased accumulation of mature DC-exos in spleen was regulated by CCR7, whose reduction led to a decrease of accumulation in spleen and attenuated inflammatory response in serum. These data provide us a new perspective to comprehensively understand exosomes, which might inherit some special functions from their parent cells and exert these functions in vivo.

Perceived risk of ischemic and bleeding events in acute coronary syndromes.

BACKGROUND: Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain. METHODS AND RESULTS: The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%-35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772-0.851] versus physician, 0.652 [95% confidence interval, 0.596-0.708]; P<0.0001). The GRACE score added to clinician intuition improved discrimination (integrated discrimination improvement, 0.0632 [SE, 0.012]; P<0.0001). Invasive management correlated with physician-estimated risk but not with GRACE risk. Among patients not at high risk by physician estimation, increased risk by GRACE score was associated with higher mortality (3.7% versus 0.8%; P<0.001). CONCLUSIONS: Objective risk assessment provides superior risk discrimination when compared with physician-estimated risk. Whether systematic use of objective risk stratification improves clinical outcomes should be studied in appropriately designed clinical trials.