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.

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.

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.

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.

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.

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.

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.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). CONCLUSIONS: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Placebo-Controlled Efficacy of Percutaneous Coronary Intervention for Focal and Diffuse Patterns of Stable Coronary Artery Disease.

[Figure: see text].

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.