Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis.

BACKGROUND: Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR. METHODS: We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE. RESULTS: The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35-2.04, p = < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06-2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20-2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07-4.05, p = 0.03). CONCLUSIONS: For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL:  https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022367312.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization.

PURPOSE: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue. METHODS: Symptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement. RESULTS: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase. CONCLUSIONS: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

Pre-stenting angiography-FFR based physiological map provides virtual intervention and predicts physiological and clinical outcomes.

BACKGROUND: Angiography-derived fractional flow reserve (FFR) (angio-FFR) has been validated against FFR and could provide virtual pullback. However, whether a physiological map can be generated by angio-FFR and its clinical value remains unclear. We aimed to investigate the feasibility of physiological map created from angio-FFR pullback and its value in predicting physiological and clinical outcomes after stenting. METHODS: An angio-FFR physiological map was generated by overlaying the virtual pullback onto coronary angiogram, to calculate physiological stenosis severity, length, and intensity (Δangio-FFR/mm). This map in combination with virtual stenting was used to predict the best-case post-percutaneous coronary intervention (PCI) angio-FFR (angio-FFRpredicted ) according to the stented segments, and this was compared with the actual achieved post-PCI angio-FFR (angio-FFRachieved ). Additionally, prognostic value of predicted angio-FFR was investigated. RESULTS: Three hundred twenty-nine vessels with paired analyzable pre- and post-PCI angio-FFR were included. Physiological map was created successfully in all vessels. After successful PCI, angio-FFRpredicted and angio-FFRachieved were significantly correlated (r = 0.82, p < 0.001) with small difference (mean difference: -0.010 ± 0.035). In the virtual PCI only covering the segment with high angio-FFR intensity, the same physiological outcome can be achieved with shorter stent length (14.1 ± 8.9 vs. 34.5 ± 15.8 mm, p < 0.001). Suboptimal angio-FFRpredicted was associated with increased risk of 2-year vessel-oriented composite endpoint (adjusted hazard ratio: 3.71; 95% confidence interval: 1.50-9.17). CONCLUSIONS: Angio-FFR pullback could provide a physiological map of the interrogated coronary vessels by integrating angio-FFR pullback and angiography. Before a PCI, the physiological map can predict the physiological and clinical outcomes after stenting.

Health effects of filtering facepiece respirators: Systematic review of pulmonary and cardiovascular effects.

Filtering facepiece respirators (FFRs) were introduced to protect the wearer by removing small particles from inspired air. FFRs are now also used to reduce the spread of transmissible agents from the wearer and are worn outside traditional healthcare and other workplaces. The COVID-19 pandemic increased concerns about potential adverse effects on wearers. A PUBMED query retrieved articles through June 2022. Abstracts and selected full-text articles were systematically reviewed by the authors. This article focuses upon cardiopulmonary physiologic effects (e.g., ventilation, CO2 elimination, oxygen uptake, and respiratory control) with emphasis upon current and potential research methods as well as summarizing results. 1985 records were identified, of which only 26% were published before 2020. FFR effects on CO2 elimination appear more likely to be significant than effects on oxygenation or cardiovascular function. While FFRs appear well tolerated by healthy persons, more research is needed for those with pulmonary or cardiac disorders, and for children. Many traditional pulmonary exercise study methods require special care when applied to filtering facepiece respirators. Studying additional parameters may explain the paradox of many subjective discomfort reports despite very limited physiologic effects.

Long-Term Outcomes of Revascularization Compared to Deferral in Stable Coronary Artery Disease: a Review.

PURPOSE OF REVIEW: The aim of this study is assessing the long-term outcomes of revascularization compared to deferral in stable coronary artery disease with available literature. RECENT FINDINGS: The overall safety of stable coronary artery disease using IFR has been well established. There have been very few studies that have examined the safety of deferral of revascularization vs revascularization. As seen in listed literature, there appears to be no difference between revascularization compared to deferral in stable coronary artery disease.

Assessing the filtration efficiency and regulatory status of N95s and nontraditional filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has severely disrupted supply chains for many types of Personal Protective Equipment (PPE), particularly surgical N95 filtering facepiece respirators (FFRs; "masks"). As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed use of industrial N95 respirators and importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of masks in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer or supplier. We then assembled a testing apparatus at a university laboratory and performed a modified test of filtration performance using KCl and ambient particulate matter on masks from hospital inventories; an accompanying website shows how to build and use the testing apparatus. RESULTS: Over 100 different makes and models of traditional and nontraditional filtering facepiece respirators (N95-type masks) were in the inventory of surveyed U.S. teaching hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many are not correctly labelled and do not perform to accepted standards and a subset are obviously dangerous; many of these masks are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers and inconsistent labeling of KN95 masks, it is difficult to distinguish between legitimate and counterfeit products. CONCLUSIONS: Many FFRs available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations to assist end users in acquiring legitimate products. Institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for regulatory agencies regarding labeling and public disclosure aimed at increasing pandemic resilience.

Safety and Long-Term Clinical Outcomes of Fractional Flow Reserve Guided Coronary Revascularisation.

BACKGROUND: Increasingly, fractional flow reserve (FFR) is employed to assess coronary artery stenoses although there is limited real world long-term outcome data with a recent report questioning its safety. This study aimed to assess the in-hospital complications and clinical outcomes up to 10 years after FFR-guided revascularisation at a tertiary Australian hospital. METHODS: The cohort comprised 274 consecutive patients undergoing FFR from 2010 to 2015 with follow-up to 2020. In-hospital complications and long-term outcomes were compared between patients with FFR≤0.80 and FFR>0.80. Major adverse cardiac events (MACE) comprised cardiac death, myocardial infarction (MI) and target vessel revascularisation (TVR). RESULTS: The FFR was ≤0.80 in 166 and >0.80 in 108 patients. Stable coronary disease was present in 95%. Revascularisation was undertaken in 86.7% of the FFR≤0.80 group and in 2.8% of the group with an FFR>0.80. In-hospital adverse events were 3.3% with no pressure wire-related coronary dissection, stroke or death. At median follow-up of 5 years, patients with FFR≤0.80 and FFR>0.80 had a similar rate of cardiac death (2.6% versus 5.0%, p=0.335) and MI (2.6% versus 6.9%, p=0.154). In the FFR>0.80 group, MACE (17.8% v 7.9%; p=0.018) and TVR (12.9% v 5.3%; p=0.033) were significantly higher. CONCLUSION: This observational study highlights the safety and long-term effectiveness of FFR-guided coronary revascularisation in patients with predominantly stable disease.

Fluoride retention in infants living in fluoridated and non-fluoridated areas: effects of weaning.

Limited knowledge is available on total fluoride exposure, excretion and retention in infants, despite the first year of human life being the critical period for dental development and risk of dental fluorosis. This study investigated total daily fluoride intake (TDFI), excretion (TDFE) and retention (TDFR) in infants living in fluoridated and non-fluoridated water areas at pre- and post-weaning stages of development. Healthy infants, aged 0-12 months, were recruited and their TDFI (mg/kg body weight (BW) per d), from diet and toothpaste ingestion, was assessed over a 3-d period using a dietary diary and tooth-brushing questionnaire. TDFE (mg/kg BW per d) was estimated by collecting 48-h urine and faeces. TDFR (mg/kg BW per d) was estimated by subtracting TDFE from TDFI. A total of forty-seven infants completed the study: sixteen at pre-weaning and thirty-one at post-weaning stages, with a mean age of 3·4 and 10·0 months, respectively. TDFI was lower in the non-fluoridated area (P<0·001) and at the pre-weaning stage (P=0·002) but higher in formula-fed infants (P<0·001). TDFE was mainly affected by type of feeding, with higher excretion in formula-fed infants (P<0·001). TDFR was lower in the non-fluoridated area (P<0·001) and at the pre-weaning stage (P<0·001) but higher in formula-fed infants (P=0·001). In conclusion, a relatively large proportion of fluoride intake is retained in the body in weaned infants. This is an important consideration in fluoride-based prevention programmes, with goals to maximise caries prevention while minimising the risk of dental fluorosis.

Assessing the efficacy of tabs on filtering facepiece respirator straps to increase proper doffing techniques while reducing contact transmission of pathogens.

NIOSH-certified N95 filtering facepiece respirators (FFRs) are used in healthcare settings as a control measure to mitigate exposures to airborne infectious particles. When the outer surface of an FFR becomes contaminated, it presents a contact transmission risk to the wearer. The Centers for Disease Control and Prevention (CDC) guidance recommends that healthcare workers (HCWs) doff FFRs by grasping the straps at the back of the head to avoid contact with the potentially contaminated surface. Adherence to proper doffing technique is reportedly low due to numerous factors including difficulty in locating and grasping the straps. This study compares the impact of tabs placed on FFR straps to controls (without tabs) on proper doffing, ease of use and comfort, and reduction of transfer of contamination to the wearer. Utilizing a fluorescent agent as a tracer to track contamination from FFRs to hand and head areas of 20 human subjects demonstrated that there was no difference in tabbed FFR straps and controls with respect to promoting proper doffing (p = 0.48), but did make doffing easier (p = 0.04) as indicated by 7 of 8 subjects that used the tabs. Seven of the 20 subjects felt that FFRs with tabs were easier to remove, while only 2 of 20 indicated that FFRs without tabs were easier to remove. Discomfort was not a factor for either FFR strap type. When removing an FFR with contaminated hands, the use of the tabs significantly reduced the amount of tracer transfer compared to straps without tabs (p = 0.012). FFRs with tabs on the straps are associated with ease of doffing and significantly less transfer of the fluorescent tracer.

Prognostic Value of Poststenting Fractional Flow Reserve After Imaging-Guided Optimal Stenting.

BACKGROUND: Prognostic value of poststenting fractional flow reserve (FFR) remains uncertain in patients undergoing an imaging-guided optimal stenting strategy. OBJECTIVES: The authors evaluated the prognostic value of poststenting FFR according to the intracoronary imaging-guided lesion preparation, stent sizing, and postdilation (iPSP) strategy to optimize stent outcomes. METHODS: Poststenting FFR assessment was performed in 1,108 lesions in 1,005 patients from the IRIS-FFR registry. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 5 years. RESULTS: At the index procedure, 326 lesions (29.4%) were treated using all 3 parts of the iPSP strategy. In the overall population, poststenting FFR was significantly associated with the risk of TVF at 5 years (per 0.01 increase of FFR, adjusted HR [aHR]: 0.94; 95% CI: 0.90-0.98; P = 0.004). Significant interaction was detected between poststenting FFR and the iPSP strategy on the risk of TVF at 5 years (P = 0.045 for interaction). In the iPSP group, poststenting FFR was not associated with the risk of TVF at 5 years (per 0.01 increase of FFR, aHR: 1.00; 95% CI: 0.96-1.05; P = 0.95), whereas a significant association between poststenting FFR and TVF at 5 years was observed in the no iPSP group (per 0.01 increase of FFR, aHR: 0.94; 95% CI: 0.90-0.99; P = 0.009). CONCLUSIONS: Poststenting FFR showed a significant association with cardiac events. However, its prognostic value appeared to be limited after the application of an imaging-guided optimal stenting strategy.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial.

BACKGROUND: The debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. OBJECTIVES: The primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. METHODS: Patients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. RESULTS: A total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). CONCLUSIONS: In CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952).

Complete revascularization of multivessel coronary artery disease in patients with ST elevation acute coronary syndrome - for whom and when? A comprehensive review.

Atherosclerosis is the most common cause of coronary steno-occlusive disease and acute myocardial infarction is the leading cause of death in industrialized countries. In patients with acute ST elevation myocardial infarction (STEMI), there is unquestionable evidence that primary percutaneous coronary intervention providing recanalization of the infarct related artery (IRA) is the preferred reperfusion strategy. Nevertheless, up to 50% of patients with STEMI have multivessel coronary artery disease defined as at least 50% stenosis exclusive of IRA. There is conflicting data regarding the optimal treatment strategy and timing in such patients. Currently, it is assumed that stable patients might benefit from complete revascularization particularly in reducing the need for future unplanned procedures but only culprit lesion should be treated during index procedure in unstable patients. In this article, we provide a comprehensive overview of this important and currently highly debated topic.

Optimal Treatment Strategy for Coronary Artery Stenoses with Grey Zone Fractional Flow Reserve Values. A Systematic Review and Meta-Analysis.

OBJECTIVES: We conducted a review and meta-analysis of published data to compare revascularization to deferral strategy for coronary lesions with grey zone fractional flow reserve (FFR). BACKGROUND: Optimal treatment for coronary stenoses with FFR values between 0.75 and 0.80, the so-called grey zone, remains a matter of debate. METHODS: We included all studies evaluating revascularization versus deferral for lesions with grey zone FFR. The primary outcome was study-defined major adverse cardiac events (MACE). Secondary outcomes were the composite of death or MI and target vessel revascularization (TVR). A total of 2362 patients were included, of whom 1181 underwent revascularization (revascularization group) and 1181 received medical treatment only (deferral group). RESULTS: After a mean follow-up period of 2.4 years, no difference was found for the primary outcome of the study-defined MACE between the two groups [RR = 1.33 (0.73-2.44), p = 0.35]. In addition, there was no difference for the secondary outcomes of death or MI and TVR between the two groups [RR = 1.39 (0.56-3.47), p = 0.48 and RR = 1.49 (0.89-2.51), p = 0.13, respectively]. CONCLUSIONS: In this meta-analysis revascularization of coronary stenoses with grey zone FFR showed no advantage over a deferral strategy in terms of study-defined MACE. Case by case judgment should be implemented to guide treatment in this special subset of patients.

Impact of intravascular ultrasound findings in patients with a post PCI fractional flow reserve ≤0.85 on 2 year clinical outcome.

BACKGROUND: Patients with a low post PCI fractional flow reserve (FFR) are at increased risk for future adverse cardiac events. The aim of the present study was to assess the impact of specific intravascular ultrasound (IVUS) findings in patients with a low post percutaneous coronary intervention (PCI) FFR on long-term clinical outcome. METHODS: In a subgroup analysis, 100 vessels with an FFR value ≤0.85 underwent post PCI IVUS to further assess the potential determinants for low post PCI FFR. No further action was taken to improve post PCI FFR. The primary endpoint of this study was the event free survival of target vessel failure (TVF) at two years in patients with a post PCI FFR ≤0.85, which was defined as a composite of cardiac death, target vessel myocardial infarction or target vessel revascularization. RESULTS: In patients with a post PCI FFR ≤0.85, TVF free survival rates were 88.5% vs. 95.5% for patients with versus without residual proximal lesions and 88.2% vs. 95.5% for patients with versus without residual distal lesions respectively (HR = 2.53, 95% confidence interval (CI) 0.52-12.25, p = .25 and HR = 2.60, 95% CI 0.54-12.59, p = .24 respectively). TVF free survival was 92.8% vs. 93.5% in patients with versus without stent underexpansion >20% (HR = 1.01, 95% CI 0.21-4.88, p = .99) and 89.3% vs. 97.8% in patients with versus without any residual focal lesion including lumen compromising hematoma (HR = 4.64, 95% CI 0.55-39.22, p = .18). CONCLUSION: Numerically higher TVF rates were observed in patients with a post PCI FFR ≤0.85 and clear focal residual disease as assessed with IVUS.