Physiological Assessment with iFR prior to FFR Measurement in Left Main Disease.

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.

Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance.

BACKGROUND: The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral. METHODS: In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem. RESULTS: At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20-0.89]; P=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%; P=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056-0.70]; P=0.012). CONCLUSIONS: In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-free ratio, the long-term clinical outcomes were significantly improved as compared with those in whom revascularization was deferred.

Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry.

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74-0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04-13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.

Angiography-derived functional assessment of left main coronary stenoses.

OBJECTIVES: We aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in left main (LM) coronary stenoses, using Fractional Flow Reserve (FFR) as reference. BACKGROUND: QFR has demonstrated a high accuracy in determining the functional relevance of coronary stenoses in non-LM. However, there is an important paucity of data regarding its diagnostic value in the specific anatomical subset of LM disease. METHODS: This is a retrospective, observational, multicenter, international, and blinded study including patients with LM stenoses. Cases with significant ostial LM disease were excluded. QFR was calculated from conventional angiograms at blinded fashion with respect to FFR. RESULTS: Sixty-seven patients with LM stenoses were analyzed. Overall, LM had intermediate severity, both from angiographic (diameter stenosis [%DS] 43.8 ± 11.1%) and functional perspective (FFR 0.756 ± 0.105). Mean QFR was 0.733 ± 0.159. Correlation between QFR and FFR was moderate (r = 0.590). Positive and negative predictive value, sensitivity and specificity were 85.4%, 64%, 85.4%, and 69.6% respectively. Classification agreement of QFR and FFR in terms of functional stenosis severity was 78.1%. Area under the receiver operating characteristics of QFR using FFR as reference was 0.82 [95% confidence interval [CI], 0.71-0.93], and significantly better than angiographic evaluation including %DS (area under the receiver-operating characteristic curve [AUC] 0.45 [95% CI, 0.32-0.58], p < 0.001) and minimum lumen diameter (AUC 0.60 [95% CI, 0.47-0.74], p < 0.001). CONCLUSIONS: Compared with FFR, QFR has acceptable diagnostic performance in determining the functional relevance of LM stenosis, being better than conventional angiographic assessment. Nonetheless, caution should be taken when applying functional angiography techniques for the assessment of LM stenosis given its particular anatomical characteristics.

Viral load of SARS-CoV-2 Omicron BA.5 is lower than that of BA.2 despite the higher infectivity of BA.5.

BACKGROUND: Sublineage BA.5 of the SARS-CoV-2 Omicron variant rapidly spread and replaced BA.2 in July 2022 in Tokyo. A high viral load can be a possible cause of high transmissibility. METHODS AND RESULTS: The copy numbers of SARS-CoV-2 in nasopharyngeal swab samples obtained from all patients visiting the hospital where this research was conducted were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Viral genotypes were determined using PCR-based melting curve analysis. Next, whole-genome sequencing was performed using approximately one fifth of the samples to verify the viral genotypes determined using PCR. Then, the copy numbers of the BA.1, BA.2, and BA.5 cases were compared. Contrary to expectations, the copy numbers of the BA.5 cases (median 4.7 × 104 copies/µL, n = 291) were significantly (p = .001) lower than those of BA.2 cases (median 1.1 × 105 copies/µL, n = 184). There was no significant difference (p = .44) between the BA.5 and BA.1 cases (median, 3.3 × 104 copies/µL; n = 215). CONCLUSION: The results presented here suggest that the increased infectivity of BA.5 is not caused by higher viral loads, but presumably by other factors such as increased affinity to human cell receptors or immune escape due to its L452R mutation.

Prediction of functional results of percutaneous coronary interventions with virtual stenting and quantitative flow ratio.

BACKGROUND: The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown. AIM: We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI). METHODS: This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years. RESULTS: We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R = 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R = 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement: -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve [AUC]: 0.856 [0.804-0.909], p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p = 0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p = 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio [HR]: 12.9 [2.32-71.3], p = 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR: 16.98 [2.33-123.29], p = 0.0051). CONCLUSIONS: rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events. CLINICAL TRIAL REGISTRATION: Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560.

Viral load of SARS-CoV-2 Omicron is not high despite its high infectivity.

Patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 has increased worldwide since the beginning of 2022 and the variant has spread more rapidly than the Delta variant, which spread in the summer of 2021. It is important to clarify the cause of the strong transmissibility of the Omicron variant to control its spread. In 694 patients with coronavirus disease 2019, the copy numbers of virus in nasopharyngeal swab-soaked samples and the viral genotypes were examined using quantitative polymerase chain reaction (PCR) and PCR-based melting curve analysis, respectively. Whole-genome sequencing was also performed to verify the viral genotyping data. There was no significant difference (p = 0.052) in the copy numbers between the Delta variant cases (median 1.5 × 105 copies/µl, n = 174) and Omicron variant cases (median 1.2 × 105 copies/µl, n = 328). During this study, Omicron BA.1 cases (median 1.1 ×105 copies/µl, n = 275) began to be replaced by BA.2 cases (median 2.3 × 105 copies/µl, n = 53), and there was no significant difference between the two groups (p = 0.33). Our results suggest that increased infectivity of the Omicron variant and its derivative BA.2 is not caused by higher viral loads but by other factors, such as increased affinity to cell receptors or immune escape.

Viral loads and profile of the patients infected with SARS-CoV-2 Delta, Alpha, or R.1 variants in Tokyo.

The rapid spread of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a serious concern worldwide in summer 2021. We examined the copy number and variant types of all SARS-CoV-2-positive patients who visited our hospital from February to August 2021 using polymerase chain reaction (PCR) tests. Whole genome sequencing was performed for some samples. The R.1 variant (B.1.1.316) was responsible for most infections in March, replacing the previous variant (B.1.1.214); the Alpha (B.1.1.7) variant caused most infections in April and May; and the Delta variant (B.1.617.2) was the most prevalent in July and August. There was no significant difference in the copy numbers among the previous variant cases (n = 29, median 3.0 × 104 copies/µl), R.1 variant cases (n = 28, 2.1 × 105 copies/µl), Alpha variant cases (n = 125, 4.1 × 105 copies/µl), and Delta variant cases (n = 106, 2.4 × 105 copies/µl). Patients with Delta variant infection were significantly younger than those infected with R.1 and the previous variants, possibly because many elderly individuals in Tokyo were vaccinated between May and August. There was no significant difference in mortality among the four groups. Our results suggest that the increased infectivity of Delta variant may be caused by factors other than the higher viral loads. Clarifying these factors is important to control the spread of Delta variant infection.

SARS-CoV-2 R.1 lineage variants that prevailed in Tokyo in March 2021.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as B.1.1.7 and B.1.351, has become a crucial issue worldwide. Therefore, we began testing all patients with COVID-19 for the N501Y and E484K mutations by using polymerase chain reaction (PCR)-based methods. Nasopharyngeal swab samples from 108 patients who visited our hospital between February and April 2021 were analyzed. The samples were analyzed using reverse transcription-PCR with melting curve analysis to detect the N501Y and E484K mutations. A part of the samples was also subjected to whole-genome sequencing (WGS). Clinical parameters such as mortality and admission to the intensive care unit were analyzed to examine the association between increased disease severity and the E484K mutation. The ratio of cases showing the 501N + 484K mutation rapidly increased from 8% in February to 46% in March. WGS revealed that the viruses with 501N + 484K mutation are R.1 lineage variants. Evidence of increased disease severity related to the R.1 variants was not found. We found that the R.1 lineage variants rapidly prevailed in Tokyo in March 2021, which suggests the increased transmissibility of R.1 variants, while they showed no increased severity.