Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Lymphatic venous anastomosis and complex decongestive therapy for lymphoedema: randomized clinical trial.

BACKGROUND: Lymphatic venous anastomosis is associated with a low incidence of lower extremity lymphoedema-associated cellulitis; however, the exact relationship is unknown. This multicentre RCT evaluated the effect of lymphatic venous anastomosis on prevention of cellulitis. METHODS: Patients with secondary lower extremity lymphoedema who underwent at least 3 months of non-operative decongestive therapy were assigned randomly to lymphatic venous anastomosis or conservative therapy. The primary and secondary outcomes were cellulitis frequency, and assessments of circumference, hardness, and pain respectively. RESULTS: Overall, 336 patients were divided into two groups: 225 in the full-analysis set (primary outcome 225; secondary outcomes 170) and 156 in the per-protocol set (primary outcome 156; secondary outcomes 110). In both analyses, lymphatic venous anastomosis with non-operative decongestive therapy was more effective in preventing cellulitis than non-operative decongestive therapy alone; the difference between groups in reducing cellulitis frequency over 6 months was -0.35 (95 per cent c.i. -0.62 to -0.09; P = 0.010) in the full-analysis set (FAS) and -0.60 (-0.94 to -0.27; P = 0.001) in the per-protocol set (PPS) Limb circumference and pain were not significantly different, but lymphatic venous anastomosis reduced thigh area hardness (proximal medial and distal and lateral proximal). Four patients experienced contact dermatitis with non-operative decongestive therapy alone. CONCLUSION: Lymphatic venous anastomosis in combination with non-operative decongestive therapy prevents cellulitis. REGISTRATION NUMBER: UMIN00025137, UMIN00031462.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

In-hospital outcomes and usage of embolic protection devices in percutaneous coronary intervention for coronary artery bypass grafts: Insights from a Japanese nationwide registry.

OBJECTIVES: We evaluated the in-hospital outcomes of percutaneous coronary intervention (PCI) for bypass graft vessels (GV-PCI) compared with those of PCI for native vessels (NV-PCI) using data from the Japanese nationwide coronary intervention registry. METHODS: We included PCI patients (N = 748,229) registered between January 2016 and December 2018 from 1,123 centers. We divided patients into three groups: GV-PCI (n = 2,745); NV-PCI with a prior coronary artery bypass graft (pCABG) (n = 23,932); and NV-PCI without pCABG (n = 721,552). RESULTS: GV-PCI implementation was low, and most cases of PCI in pCABG patients were performed in native vessels (89.7%) in contemporary Japanese practice. The risk profile of patients with pCABG was higher than that of those without pCABG. Consequently, GV-PCI patients had a significantly higher in-hospital mortality than NV-PCI patients without pCABG after adjusting for covariates (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.66-3.36, p < .001). Of note, embolic protection devices (EPDs) were used in 18% (n = 383) of PCIs for saphenous vein grafts (SVG-PCI) with a significant variation in its use among institutions (number of PCI: hospitals that had never used an EPD vs. EPD used one or more times = 240 vs. 345, p < .001). The EPDs used in the SVG-PCI group had a significantly lower prevalence of the slow-flow phenomenon after adjusting for covariates (OR 0.45, 95% CI 0.21-0.91, p = .04). CONCLUSION: GV-PCI is associated with an increased risk of in-hospital mortality. EDP use in SVG-PCI was associated with a low rate of the slow-flow phenomenon. The usage of EPDs during SVG-PCI is low, with a significant variation among institutions.

Diagnostic Performance of High-Resolution Intravascular Ultrasound for Abnormal Post-Stent Findings After Stent Implantation　- A Comparison Study Between High-Resolution Intravascular Ultrasound and Optical Coherence Tomography.

BACKGROUND: High-resolution intravascular ultrasound (HR-IVUS) is the most recently developed IVUS technology, which allows the detailed assessment of intravascular structures. The aim of this study was to evaluate the diagnostic performance of HR-IVUS in the detection of abnormal post-stent findings.Methods and Results:Patients with acute coronary syndrome underwent both HR-IVUS and optical coherence tomography (OCT) for post-stent evaluations. Quantitative measurements for stented segments and qualitative assessments for abnormal post-stent findings (stent edge dissection, intrastent tissue protrusion, and incomplete stent apposition [ISA]) were performed. Forty-seven patients underwent both HR-IVUS and OCT after stent implantation. HR-IVUS identified a larger minimal lumen area and a larger minimal lumen diameter than OCT (6.66±1.98 mm2vs. 5.61±1.79 mm2and 2.87±0.42 mm vs. 2.63±0.43 mm, respectively; both P<0.001). The sensitivity of HR-IVUS for the identification of stent edge dissection, intrastent tissue protrusion, and ISA were 20.0%, 48.9%, and 27.2%, respectively. CONCLUSIONS: In terms of post-stent evaluation, the diagnostic performance of HR-IVUS remains insufficient. Abnormal post-stent findings might be underestimated when performing HR-IVUS due to its low sensitivity.

Independent predictors of discordance between the resting full-cycle ratio and fractional flow reserve.

The resting full-cycle ratio (RFR), a novel resting index, is well correlated with and shows good diagnostic accuracy to the fractional flow reserve (FFR). However, discordance results between the RFR and FFR have been observed to occur in about 20% of cases. This study aimed to clarify the prevalence and factors of discordant results between the RFR and FFR through a direct comparison of these values in daily clinical practice. A total of 220 intermediate coronary lesions of 156 consecutive patients with RFR and FFR measurements were allocated to four groups according to RFR and FFR cutoff values. We compared the angiographic, clinical, and hemodynamic variables among the groups. Discordant results between the RFR and FFR were observed in 19.6% of vessels, and the proportion of discordant results was significantly higher in the left main trunk and left anterior descending artery (LM + LAD) than in non-LAD vessels (25.2% vs. 12.3%, p = 0.006). In the multivariable regression analysis, LM + LAD location, hemodialysis, and peripheral artery disease were associated with a low RFR among patients with a high FFR. Conversely, the absence of diabetes mellitus and the presence of higher hemoglobin levels were associated with a higher RFR among patients with a low FFR. Specific angiographic and clinical characteristics such as LM + LAD location, hemodialysis, peripheral artery disease, and absence of diabetes mellitus and anemia can be independent predictors of physiologic discordance between the RFR and FFR.

Impact of antiplatelet therapy on tissue prolapse at super acute phase after stenting: serial OCT study in acute coronary syndrome patients.

Although drug-eluting stents have improved clinical outcomes, percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remains a challenging procedure in terms of thrombus management. A new-generation P2Y12 receptor inhibitor, prasugrel, provides more rapid and potent antiplatelet action compared with clopidogrel. Prasugrel achieved significant reduction of ischemic events compared with clopidogrel in ACS. The aim of this optical coherence tomography (OCT) study was to evaluate temporal changes in tissue prolapse after stenting under different antiplatelet regimens (aspirin plus prasugrel or clopidogrel) in ACS patients. A total of 119 ACS patients were randomized to either prasugrel or clopidogrel at the time of PCI. OCT analysis was available in 119 patients at baseline (just after stenting), 77 patients at 2 weeks, and 62 patients at 4 months after stenting. Cross-sectional analysis for every 1 mm was performed at in-stent and adjacent reference segment. Tissue prolapse area was calculated by lumen area minus stent area within the stented segment. Baseline patient and procedural characteristics were not different between the prasugrel and clopidogrel groups. Tissue prolapse area was significantly lower in the prasugrel compared with the clopidogrel group after stenting (0.24 ± 0.23 vs. 0.36 ± 0.23 mm2, p = 0.003) and at 2 weeks (0.11 ± 0.13 vs. 0.19 ± 0.16 mm2, p = 0.005). However, there was no significant difference at 4 months. In conclusion, our study suggests prasugrel was effective in reducing tissue prolapse in the super acute phase in ACS patients compared with clopidogrel. However, the effect of tissue prolapse reduction was not different up to 4 months follow-up.

Clinical feasibility of resting full-cycle ratio as a unique non-hyperemic index of invasive functional lesion assessment.

The resting full-cycle ratio (RFR) is a new physiologic index to assess myocardial ischemia. RFR and fractional flow reserve (FFR), the conventionally used index, have not been directly compared in evaluating the entire cardiac cycle. Accordingly, we aimed to compare the diagnostic performance of RFR directly with FFR and clarify the clinical feasibility of RFR as a unique non-hyperemic index in evaluating the cardiac cycle. The diagnostic performance of RFR was compared with FFR using an automated online calculation software. A total of 156 consecutive patients with 220 intermediate lesions were enrolled. RFR showed significant correlation with FFR (r = 0.774, p < 0.001). RFR systole and RFR diastole did also with FFR (r = 0.918, p < 0.001, and r = 0.733, p < 0.001, respectively). With FFR < 0.80 as a reference standard, RFR showed good diagnostic accuracy (DA: 80.5%), similar DA between RFR systole and RFR diastole (79.6% and 87.5%, p = 0.58, respectively), and good DA in any lesion locations, especially in non-left anterior descending coronary artery (LAD) lesions (73.7% and 87.6% for LAD vs. non-LAD, p < 0.05, respectively). RFR is a feasible and reliable non-hyperemic index regardless of the difference in cardiac cycle in evaluating physiological lesion severity in daily practice.

Diagnostic Performance of High-Resolution Intravascular Ultrasound for the Detection of Plaque Rupture in Patients With Acute Coronary Syndrome.

BACKGROUND: The new 60-MHz high-resolution intravascular ultrasound (HR-IVUS) is the next-generation IVUS technology, providing higher image resolution than conventional IVUS. It gives clear images of plaque morphology and can discriminate the underlying mechanism of acute coronary syndrome (ACS). Our study aimed to evaluate the diagnostic performance of 60-MHz HR-IVUS in the detection of plaque rupture in patients with ACS.Methods and Results:Patients with ACS who underwent percutaneous coronary intervention for de novo native coronary artery lesions were enrolled. Both HR-IVUS and optical coherence tomography (OCT) were performed for the culprit lesions prior to interventions other than aspiration thrombectomy. Keeping plaque rupture detected by OCT as the gold standard, the diagnostic performance of HR-IVUS was evaluated. Overall, 70 patients underwent both HR-IVUS and OCT examinations. Of these, imaging assessments by HR-IVUS were available for all 70 patients (100%), and those by OCT were available for 54 patients (77.1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HR-IVUS for identifying a plaque rupture were 84.8%, 57.1%, 75.7%, 70.6%, and 74.1%, respectively. CONCLUSIONS: HR-IVUS had high sensitivity, but modest specificity for identifying OCT-derived plaque rupture. Compared with results from previous conventional IVUS studies, HR-IVUS might have increased ability to detect OCT-derived plaque rupture, but there is still substantial scope for improvement, especially in the specificity.

Impact of vascular access site on procedural time of endomyocardial biopsy.

Endomyocardial biopsy (EMB) is widely used for the diagnosis of unexplained ventricular dysfunction and for assessment of cardiac allograft rejection. But, the impact of vascular access site on procedural time of EMB is not well-known. From February 2014 to May 2016, consecutive patients requiring EMB were prospectively enrolled in this study. Vascular access, by either the jugular or femoral vein, was randomly assigned. EMB was randomly performed by 3 pre-identified physicians based on practical experience in EMB. Each case was required to obtain at least 3 samples. The primary endpoint was to compare the total time spent in acquiring EMB from the right ventricular septum between the jugular and femoral vein access groups. The secondary endpoints were evaluation of each set (1st to 3rd attempt) of EMB times and safety. In addition, factors affecting the EMB procedural times were evaluated. A total of 49 consecutive patients requiring EMB (3.9 attempts/patient) were enrolled (the jugular group: 23, the femoral group: 26), and 156 myocardial samples (3.2 samples/patient) were obtained. There were no significant differences in total biopsy procedural time between the 2 groups (16.3 ± 7.4 vs. 20.8 ± 9.9 min, p = 0.075). Independent predictors for longer procedural time of the 1st attempt included femoral access, non-expert operators, and larger right atrium according to multiple linear regression analysis. The complication rates were not significantly different between the 2 groups, except for catheter kinking as a technical factor. Total biopsy time was not significantly different between the jugular and femoral venous access groups. However, the 1st attempt EMB procedural time by non-expert operators was longer when using the femoral approach, especially in cases involving a larger right atrium diameter.

Early-Phase Vascular Healing of Bioabsorbable vs. Durable Polymer-Coated Everolimus-Eluting Stents in Patients With ST-Elevation Myocardial Infarction　- 2-Week and 4-Month Analyses With Optical Coherence Tomography.

BACKGROUND: Despite the revolution of coronary stents, there remain concerns about the risk of stent thrombosis, especially in patients with ST-elevation myocardial infarction (STEMI). The present study compared early vascular healing as a contributing factor to reducing stent thrombosis between Xience everolimus-eluting stents (X-EES) and Synergy everolimus-eluting stents (S-EES) in patients with STEMI. Methods and Results: The present study included 47 patients with STEMI requiring primary percutaneous coronary intervention with X-EES (n=25) or S-EES (n=22). Optical coherence tomography (OCT) assessments of the stented lesions were performed 2 weeks and 4 months after stent implantation. Neointimal strut coverage, malapposition and the frequency of thrombus formation were evaluated. In the 2-week OCT analysis, the proportion of covered struts in S-EES (42.4±15.4%) was significantly higher than in X-EES (26.3±10.1%, P<0.001). In the 4-month OCT analysis, the proportion of covered struts in S-EES (72.2±17.9%) was still significantly higher than in X-EES (62.0±14.9%, P=0.04). CONCLUSIONS: Compared with X-EES, S-EES showed a higher proportion of covered struts in the early phase after stent implantation for STEMI patients.

Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients with Chronic Kidney Disease.

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

Tissue characteristics of neointima in late restenosis: integrated backscatter intravascular ultrasound analysis for in-stent restenosis.

Although late restenosis is one of the long-term complications of stent implantation, its pathogenesis has not been fully elucidated. For consecutive patients who developed in-stent restenosis (ISR) after stent implantation, integrated backscatter (IB) intravascular ultrasound was performed for ISR lesions. The tissue characteristics of neointima within the stented segment were compared between lesions with early restenosis and those with late restenosis. Of 73 ISR lesions arising after sirolimus-eluting stent (SES; n = 25) or bare-metal stent (BMS; n = 48) implantation, early and late restenosis were documented in 52 and 21 lesions, respectively. A higher prevalence of late restenosis was observed after SES implantation than after BMS implantation (60.0 vs. 12.5 %; p < 0.001). The duration between stent implantation and late restenosis was significantly shorter after SES implantation than after BMS implantation (57.0 ± 22.1 vs. 124.4 ± 19.6 months; p < 0.001). Percent low-IB volume was significantly higher in the neointima of late restenosis than in that of early restenosis (29.9 ± 9.9 vs. 19.8 ± 11.3 %; p < 0.001). Significantly more low-IB tissue was observed in the neointima of late restenosis than in that of early restenosis, suggesting atherosclerotic progression in late phase after stent implantation as a possible mechanism of late restenosis.

Impact of lesion characteristics on the prediction of optimal poststent fractional flow reserve.

BACKGROUND: Poststent fractional flow reserve (FFR) is a useful indicator of optimal percutaneous coronary intervention, and higher poststent FFR is associated with favorable long-term clinical outcome. However, little is known about the factors influencing poststent FFR. The purpose of this study was to determine the impact of lesion characteristics on poststent FFR. METHODS: For patients who had scheduled stent implantation for stable angina, FFR measurements at maximum hyperemia were performed before and after coronary stent implantation. As one of lesion characteristics, the FFR pressure drop pattern was evaluated and classified as either an abrupt or a gradual pattern according to the pullback curve of FFR. RESULTS: A total of 205 lesions with physiological significant stenosis were evaluated. Fractional flow reserve value increased from 0.67±0.10 to 0.87±0.07 after stent implantation. Optimal poststent FFR was achieved in 75 lesions (36.6%). Logistic regression analysis demonstrated that optimal poststent FFR was positively correlated with an abrupt pressure drop pattern (hazard ratio [HR] 2.11, 95% CI 1.06-4.15, P=.03) and prestent FFR (HR 1.04, 95% CI 1.03-2.04, P=.03; per 0.1 increase), and negatively correlated with lesion localization to the left anterior descending artery (HR 0.18, 95% CI 0.09-0.36, P<.0001). The c statistic for predicting optimal poststent FFR was 0.763 (95% CI 0.702-0.819). CONCLUSION: Abrupt pressure drop patterns, prestent FFR, and lesion localization to the left anterior descending artery were independent predictors of optimal poststent FFR.

Noninvasive mathematical analysis of spectral electrocardiographic components for coronary lesions of intermediate to obstructive stenosis severity-relationship with classic and functional SYNTAX score.

OBJECTIVES: The aim of this study was to evaluate the relationship between the multifunction cardiogram (MCG), and SYNTAX score (SS) and functional SYNTAX score (FSS) in detecting the presence of intermediate to obstructive coronary lesions. BACKGROUND: Performing coronary angiography (CAG) and measuring fractional flow reserve (FFR) to calculate the SS and FSS is inherently invasive and adds complexity. METHODS: The MCG was obtained and analyzed before performing CAG in 87 consecutive subjects with suspected coronary artery disease who were scheduled for elective CAG. The patients were divided into three groups according to risk based on high, borderline, and low MCG scores. The SS was determined, as well as FSS but only by counting lesions prone to functional ischemia (FFR ≤ 0.8). The relationship between the MCG and the SS and FSS was evaluated. RESULTS: The MCG was the only test significantly associated with the SS (odds ratio, 2.92 [1.60 - 5.31], P < 0.001) and FSS (odds ratio, 3.66 [1.95 - 6.87], P < 0.001). A high MCG score had a specificity of 92.6% (89.0-96.2%) and 92.3% (89.0-95.6%), and a predictive accuracy of 72.4% (67.6-77.2%) and 82.8% (78.7-86.8%) for the prediction of SS and FSS, respectively. CONCLUSIONS: The MCG showed high specificity and predictive accuracy especially for the FSS, suggesting that it is useful not only in identifying functionally significant ischemia but also in reducing unnecessary CAGs.