Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis. METHODS AND RESULTS: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

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.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

Late lumen enlargement induced by drug coated balloon in the patient with PTFE-covered stent restenosis.

We report a case of percutaneous coronary intervention with drug coated balloon (DCB) for the in-stent restenosis of polytetrafluoroethylene-covered stent. One year follow-up angiography was excellent and in-stent lumen enlargement compared with the postprocedure and 6-months follow-up was demonstrated by optical coherent tomography. This case suggested the utility of DCB as a therapeutic option for covered-stent restenosis.

Novel Use of GuideLiner with a Low-Profile Balloon for the Retrieval of Disrupted Balloon Catheter.

We report a case of successful percutaneous retrieval of an unexpectedly disrupted balloon catheter using GuideLiner and a low-profile balloon. The procedure and the mechanism of this novel technique were described in detail with ex-vivo testing. This case demonstrated the utility of the combination of GuideLiner and low-profile balloon as a bail-out for intravascular foreign body.

Impact of rotational atherectomy on heavily calcified, unprotected left main disease.

BACKGROUND: There is little data on percutaneous coronary intervention (PCI) using rotational atherectomy (Rota) for severely calcified unprotected left main (ULM) lesions. METHODS AND RESULTS: Between January 2005 and August 2011, 64 consecutive patients who underwent drug-eluting stent implantation using Rota were retrospectively evaluated. Of these, 54.7% and 20.3% patients had diabetes and were undergoing hemodialysis (HD), respectively. The mean EuroSCORE and SYNTAX score was 5.6 and 35.4, respectively. Procedural success, defined as residual stenosis <30%, was achieved in 95.3% of patients without fatal complications. Periprocedural myocardial infarction occurred in 7.8% patients. At the 1-year follow up, cardiac death was observed in 6.3% of patients, and target lesion revascularization (TLR) and TLR in the main branch (TLR-MB) were required in 18.8% and 10.9% patients, respectively. Optimal stent expansion was achieved in the majority of 33 patients with available intravascular ultrasound (IVUS) data. However, 5 of 9 HD patients who underwent IVUS required TLR-MB despite optimal stent expansion. The rate of TLR-MB was significantly lower in the non-HD patients than in the HD patients (2.1% vs. 46.2%; P=0.003). CONCLUSIONS: PCI using Rota for calcified ULM lesions might guarantee high procedural success and a low complication rate. Although acceptable results were obtained at the 1-year follow up for non-HD patients, the rate of TLR-MB was considerably high for HD patients despite optimal stent expansion.

Exercise-induced vasospastic angina diagnosed with a hand grip test in the catheterization laboratory: a case report.

Background: Exercise-induced vasospastic angina (VSA) is a relatively uncommon clinical scenario and is difficult to diagnose in the catheterization laboratory. Case summary: A 61-year-old Japanese man presented to our hospital with complaints of angina upon exertion in the morning. Neither a 12-lead electrocardiogram nor an echocardiogram showed any abnormal findings. Invasive coronary angiogram revealed moderate stenosis in the left anterior descending coronary artery. A hand grip test was performed, during which the patient experienced chest pain, and coronary angiogram showed coronary spasm at the site of organic stenosis with delayed coronary flow. Intracoronary nitrates (300 ug) were administered, resulting in the release of coronary spasm. Conclusion: The hand grip test may serve as a useful method for diagnosing exercise-induced VSA in the catheterization laboratory.

State-of-the-art percutaneous coronary intervention for left main coronary artery disease in Japan.

Percutaneous coronary intervention for left main coronary artery disease (LM-PCI) represents a high-risk yet life-saving procedure that has evolved significantly over the years. This review outlines the current state-of-the-art practices for LM-PCI in Japan in detail, emphasizing the integration of coronary physiology and intracoronary imaging alongside with evidence-based standardized technique using latest drug-eluting stents. These advancements enable precise lesion assessment, stent sizing, and optimal deployment, thereby enhancing procedural safety and efficacy. Despite discrepancies between current guidelines favoring coronary artery bypass grafting and real-world practice trends towards increased LM-PCI adoption, particularly in elderly populations with multiple comorbidities, careful patient selection and procedural planning are critical. Future perspectives include further refining LM-PCI through conducting randomized controlled trials integrating advanced techniques and addressing the issue of ostial left circumflex lesions and nationwide standardization of medical care for LM disease.

A Systematic Approach to the Evaluation of the Coronary Microcirculation Using Bolus Thermodilution: CATH CMD.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

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.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually.

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

Impact of Left Ventricular Outflow Tract Obstruction on Coronary Physiological Assessment.

Hypertrophic cardiomyopathy which is known to occasionally have coronary artery disease as concomitant disease may require coronary physiological assessment (Okayama et al., 2015; Shin et al., 2019 [1,2]). However, no study clarified the impact of left ventricular outflow tract obstruction on coronary physiological assessment. Herein, a case of hypertrophic obstructive cardiomyopathy concomitant with moderate coronary lesion was reported, in which dynamic change of physiological values was observed during pharmacological intervention. Specifically, fractional flow reserve (FFR) and resting full-cycle ratio (RFR) changed in an opposite fashion when the left ventricular outflow tract pressure gradient was decreased by intravenous propranolol and cibenzoline: in FFR from 0.83 to 0.79 and in RFR from 0.73 to 0.91. Cardiologists should pay attention to the presence of concomitant cardiovascular disorders in interpreting coronary physiological data.

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.

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.

Predictors and outcomes of ischemia-driven target lesion revascularization in deferred lesion based on fractional flow reserve: a multi-center retrospective cohort study.

Background: Fractional flow reserve (FFR) has become the gold standard for diagnosing ischemia in angiographically intermediate epicardial coronary artery stenosis. This study investigated the clinical outcomes and predictors of revascularization deferral based on FFR. Methods: In this retrospective cohort study, we assessed 474 lesions (440 patients) where revascularization was deferred based on the FFR value. Minimum lumen diameter and %-diameter stenosis were measured. Calcification was graded as none, mild, moderate, or heavy. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score I was also determined. The primary outcome was ischemia-driven target lesion revascularization (TLR) in deferred lesions within 3 years. Patients were also assigned into two groups based on FFR value. Results: The average age of the patients was 69.7±10.4 years. The average FFR value was 0.86±0.05. Stable angina pectoris was noted in 298 (67.7%) cases, and in-stent restenosis (ISR) was present in 28 (5.9%). The average SYNTAX score was 7.2±4.2. The 3-year ischemia-driven TLR was 18 lesions (3.8%). Cox proportional hazard model revealed that the SYNTAX score and ISR were independent predictors for TLR in deferred lesions [hazard ratio (HR) =1.10, 95% confidential interval (CI): 1.01-1.19, P=0.03; HR =6.33; 95% CI: 2.25-17.8, P<0.01, respectively]. The deferral group, with a low FFR value, tended to have higher TLR rates than other groups. Conclusions: Lesions with lower FFR values were associated with a higher incidence of ischemia-driven TLR than those with higher FFR values. SYNTAX score and ISR were predictors for ischemia-driven TLR at 3 years in the deferred lesions.

Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98). CONCLUSIONS: In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Correlation of Intravascular Ultrasound and Instantaneous Wave-Free Ratio in Patients With Intermediate Left Main Coronary Artery Disease.

BACKGROUND: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. METHODS: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm2 was used as the cutoff for significant disease. RESULTS: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P<0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P<0.0001). The correlation was not significantly different when the body surface area was considered. CONCLUSIONS: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.

Inter-observer differences in interpretation of coronary pressure-wire pullback data by non-expert interventional cardiologists.

The physiological pattern of coronary artery disease as determined by pressure-wire (PW)-pullback is important for decision-making of revascularization and risk stratification of patients. However, it remains unclear whether inter-observer differences in interpreting PW-pullback data are subject to the expertise of physicians. This study sought to investigate the subjectivity of this assessment among non-experts. Expert interventional cardiologists classified 545 PW-pullback traces into physiologically focal or physiologically diffuse disease pattern. Defining expert-consensus as the reference standard, we evaluated ten non-expert doctors' classification performance. Observers were stratified equally by two ways: (i) years of experience as interventional cardiologists (middle-level vs. junior-level) and (ii) volume of institutions where they belonged to (high-volume center vs. low-volume center). When judged against the expert-consensus, the agreement of non-expert observers in assessing physiological pattern of disease (focal or diffuse) ranged from 69.1 to 85.0% (p for heterogeneity < 0.0001). There was no evidence for a moderating effect of years of experience; the pooled accuracy of middle-level doctors was 78.8% (95% confidential interval [CI] 72.8-84.7%) vs. 79.1% for junior-level doctors (95% CI 75.9-82.2%, p = 0.95 for difference). On the other hand, we observed a significant moderating effect of center volume. Accuracy across non-experts in high-volume centers was 82.7% (95% CI 80.3-85.1%) vs. 75.1% for low-volume centers (95% CI 71.9-78.3%, p = 0.0002 for difference). Interpretation of PW-pullback by non-expert interventional cardiologists was considerably subjective.