Single versus two-stent strategies for coronary bifurcation lesions: a systematic review and meta-analysis of randomized trials with long-term follow-up

Background: The majority of coronary bifurcation lesions are treated with a provisional single‐stent strategy rather than an up‐front 2‐stent strategy. This approach is supported by multiple randomized controlled clinical trials with short‐ to medium‐term follow‐up; however, long‐term follow‐up data is evolving from many data sets. Methods and Results: Meta‐analysis of randomized controlled trials evaluating long‐term outcomes (≥1 year) according to treatment strategy for coronary bifurcation lesions. Nine randomized controlled trials with 3265 patients reported long‐term clinical outcomes at mean weighted follow‐up of 3.1±1.8 years. Provisional single stenting was associated with lower all‐cause mortality (2.94% versus 4.23%; risk ratio: 0.69; 95% confidence interval, 0.48–1.00; P=0.049; I2=0). There was no difference in major adverse cardiac events (15.8% versus 15.4%; P=0.79), myocardial infarction (4.8% versus 5.5%; P=0.51), target lesion revascularization (9.3% versus 7.6%; P=0.19), or stent thrombosis (1.8% versus 1.6%; P=0.28) between the groups. Prespecified sensitivity analysis of long‐term mortality at a mean of 4.7 years of follow‐up showed that the provisional single‐stent strategy was associated with reduced all‐cause mortality (3.9% versus 6.2%; risk ratio: 0.63; 95% confidence interval, 0.42–0.97; P=0.036; I2=0). Conclusions: Coronary bifurcation percutaneous coronary intervention using a provisional single‐stent strategy is associated with a reduction in all‐cause mortality at long‐term follow‐up

The Nature of Composite LINER/HII Galaxies, As Revealed from High-Resolution VLA Observations

A sample of 37 nearby galaxies displaying composite LINER/HII and pure HII spectra was observed with the VLA in an investigation of the nature of their weak radio emission. The resulting radio contour maps overlaid on optical galaxy images are presented here, together with an extensive literature list and discussion of the individual galaxies. Radio morphological data permit assessment of the ``classical AGN'' contribution to the global activity observed in these ``transition'' LINER galaxies. One in five of the latter objects display clear AGN characteristics: these occur exclusively in bulge-dominated hosts.Comment: 31 pages, 27 figures, accepted by ApJ

Extremely hypomorphic and severe deep intronic variants in the <i>ABCA4</i> locus result in varying Stargardt disease phenotypes

Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of the ABCA4 locus in STGD1 patients identifies two expected disease-causing alleles in ∼75% of patients and only one mutation in ∼15% of patients. Recently, many possibly pathogenic variants in deep intronic sequences of ABCA4 have been identified in the latter group. We extended our analyses of deep intronic ABCA4 variants and determined that one of these, c.4253+43G&gt;A (rs61754045), is present in 29/1155 (2.6%) of STGD1 patients. The variant is found at statistically significantly higher frequency in patients with only one pathogenic ABCA4 allele, 23/160 (14.38%), MAF = 0.072, compared to MAF = 0.013 in all STGD1 cases and MAF = 0.006 in the matching general population (P &lt; 1 × 10−7). The variant, which is not predicted to have any effect on splicing, is the first reported intronic “extremely hypomorphic allele” in the ABCA4 locus; that is, it is pathogenic only when in trans with a loss-of-function ABCA4 allele. It results in a distinct clinical phenotype characterized by late onset of symptoms and foveal sparing. In ∼70% of cases the variant was allelic with the c.6006-609T&gt;A (rs575968112) variant, which was deemed nonpathogenic. Another rare deep intronic variant, c.5196+1056A&gt;G (rs886044749), found in 5/834 (0.6%) of STGD1 cases is, conversely, a severe allele. This study determines pathogenicity for three noncoding variants in STGD1 patients of European descent accounting for ∼3% of the disease. Defining disease-associated alleles in the noncoding sequences of the ABCA4 locus can be accomplished by integrated clinical and genetic analyses.</jats:p

Evaluation of the implementation of a "Pediatric Feasibility Assessment for Transplantation" tool in children and adolescents at Red Cross War Memorial Children's Hospital, Cape Town, South Africa

BACKGROUND: Kidney transplantation remains the treatment of choice for children with kidney failure (KF). In South Africa, kidney replacement therapy (KRT) is restricted to children eligible for transplantation. This study reports on the implementation of the Paediatric Feasibility Assessment for Transplantation (pFAT) tool, a psychosocial risk score developed in South Africa to support transparent transplant eligibility assessment in a low-resource setting. METHODS: Single-center retrospective descriptive analysis of children assessed for KRT using pFAT tool from 2015 to 2021. RESULTS: Using the pFAT form, 88 children (median [range] age 12.0 [1.1 to 19.0] years) were assessed for KRT. Thirty (34.1%) children were not listed for KRT, scoring poorly in all domains, and were referred for supportive palliative care. Fourteen of these 30 children (46.7%) died, with a median survival of 6 months without dialysis. Nine children were reassessed and two were subsequently listed. Residing >300 km from the hospital (p = .009) and having adherence concerns (p = .003) were independently associated with nonlisting. Of the 58 (65.9%) children listed for KRT, 40 (69.0%) were transplanted. One-year patient and graft survival were 97.2% and 88.6%, respectively. Only one of the four grafts lost at 1-year posttransplant was attributed to psychosocial issues. CONCLUSIONS: Short-term outcomes among children listed using the pFAT form are good. Among those nonlisted, the pFAT highlights specific psychosocial/socioeconomic barriers, over which most children themselves have no power to change, which should be systemically addressed to permit eligibility of more children and save lives

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Exposure to Stress and Air Pollution from Bushfires during Pregnancy: Could Epigenetic Changes Explain Effects on the Offspring?

Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.Vanessa Murphy is supported by an Investigator Grant from the Medical Research Future Fund (grant ID 1196252)

Randomized Comparison of Fractional Flow Reserve and Instantaneous Wave Free Ratio in Serial Disease

BackgroundFractional flow reserve (FFR) and the instantaneous wave-free ratio (iFR) identify arteries that benefit from percutaneous coronary intervention (PCI). FFR or iFR gradients on pullback are often used to predict the physiological result (FFRΔ or iFRΔ), but this approach is unvalidated.ObjectivesThe aim of this study was to compare the accuracy of FFRΔ, iFRΔ and FFRcalc (a mathematical solution incorporating interaction between lesions) for predicting post-PCI physiology in serial or diffuse disease.MethodsPatients with a focal target lesion and either a second focal lesion or a diffusely diseased segment in the same vessel were randomized to FFR- vs iFR-guided PCI ( ISRCTN18106869). FFR and iFR pullbacks were performed, with operators blinded to one modality. Following target lesion PCI, FFR and iFR were remeasured. The primary outcome was the error in predicted post-PCI physiology compared with actual values.ResultsA total of 87 patients were randomized to FFR (n = 45) or iFR (n = 42). Median FFR and iFR were 0.70 (Q1-Q3: 0.62 to 0.78) and 0.81 (Q1-Q3: 0.68 to 0.90) at baseline and 0.82 (Q1-Q3: 0.74 to 0.87) and 0.89 (Q1-Q3: 0.83 to 0.93) after target lesion PCI. The predictive errors were 12% (6% to 17%) for FFRΔ, 4% (0% to 9%; P &lt; 0.001) for iFRΔ, and −5% (−18% to 8%; P = 0.427) for FFRcalc. Significant residual disease was missed in 36% of cases with FFRΔ, 34% with iFRΔ, and 14% with FFRcalc.ConclusionsFFR and iFR pullback gradients overestimate the benefit of target lesion PCI and can miss residual ischemia in one-third of patients. FFR or iFR should be routinely repeated post-PCI in serial disease.<br/

Differential improvement in angina and health-related quality of life after PCI in focal and diffuse coronary artery disease

Background: An increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief. Objectives: The aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG). Methods: This is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score &lt;100. Results: A total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P &lt; 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020). Conclusions: Residual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve [TARGET-FFR]; NCT03259815)

1-year outcomes of angina management guided by invasive coronary function testing (CorMicA)

Objectives: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease. Background: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. Methods: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure–facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up. Results: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p &lt; 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803). Conclusions: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294

Ischemia and no obstructive coronary artery disease: prevalence and correlates of coronary vasomotion disorders

Background: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA). Methods: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3–3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P&lt;0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041). Results: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7–33.0]; P=0.008) and typical angina (OR, 2.7 [1.1–6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9–7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8–32.7]; P&lt;0.001) and age (OR, 1.1 per year, [1.0–1.2]; P=0.032]. Conclusions: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity