Masahiro Hada

Diagnostic and Prognostic Efficacy of Coronary Flow Capacity Obtained Using Pressure-Temperature Sensor–Tipped Wire–Derived Physiological Indices

OBJECTIVES This study aimed to evaluate the feasibility and efficacy of pressure-temperature sensor-tipped wire-derived coronary flow capacity (PTW-CFC) for assessing flow impairment and prognosis. BACKGROUND CFC provides an integrated coronary physiological assessment in which coronary flow reserve and coronary flow during hyperemia are organized. METHODS A total of 643 native de novo lesions for which physiological assessments were performed using a PressureWire (St. Jude Medical, St. Paul, Minnesota) in patients with stable coronary artery disease were identified. The entire cohort was stratified by PTW-CFC according to the well-validated thresholds of coronary flow reserve and the corresponding inverse of thermodilution-derived mean transit time under hyperemia. Coronary physiological indices and the prevalence of major adverse cardiac events (MACE) were assessed according to PTW-CFC categories. Furthermore, in patients who underwent percutaneous coronary intervention (PCI), post-PCI PTW-CFC categorization was performed and clinical outcomes were evaluated. RESULTS PTW-CFC categorization efficiently discriminated previously validated coronary physiological parameters for functional stenosis severity and microvascular dysfunction. MACE rates during follow-up (2.4 years) were significantly associated with advanced impairment of PTW-CFC except for severely reduced PTW-CFC. In the subgroup analysis of patients with severely reduced pre-PCI PTW-CFC who underwent successful PCI, MACE incidence was significantly frequent in patients with post-PCI non-normal PTW-CFC compared with those with post-PCI normal PTW-CFC. CONCLUSIONS PTW-CFC mapping was feasible, provided accurate stratifications of coronary flow impairment, and may predict MACE. Combined analysis involving PTW-CFC and fractional flow reserve may enrich the clinical implication of integrated coronary physiology and may help predict prognosis.

Significance of Microvascular Function in Visual—Functional Mismatch Between Invasive Coronary Angiography and Fractional Flow Reserve

Background Despite a moderate correlation between angiographical stenosis and physiological significance, the mechanism of discordance has not been fully elucidated, particularly regarding the significance of microvascular function. This study sought to clarify whether microvascular function affects visual‐functional mismatch between quantitative coronary angiography (QCA) and fractional flow reserve (FFR). Methods and Results We assessed QCA, FFR, coronary flow reserve, and the index of microcirculatory resistance in 849 non‐left‐main coronary lesions with visually estimated intermediate stenoses from 532 patients. Clinical and lesion‐specific characteristics and physiological parameters associated with mismatch and reverse mismatch were studied. Coronary flow reserve and index of microcirculatory resistance showed a weak, but significant, correlation with FFR (R=0.306, P<0.001 and R=0.158, P<0.001, respectively). Four hundred twenty‐two lesions were visually nonsignificant (diameter stenosis assessed by QCA [QCA‐DS] ≤50%) and 427 lesions were visually significant (QCA‐DS >50%). Among visually nonsignificant lesions, FFR ≤0.80 (reverse mismatch) was observed in 129 lesions (30.6%). Among visually significant lesions, FFR >0.80 (mismatch) were observed in 179 lesions (41.9%). The significant predictors of reverse mismatch were male sex, nonculprit lesions of acute coronary syndrome, left anterior descending artery location, smaller QCA reference diameter, greater QCA‐DS, lower coronary flow reserve, and lower index of microcirculatory resistance. Mismatch was associated with right coronary artery location, greater QCA reference diameter, smaller QCA‐DS, lesion length, higher coronary flow reserve, and higher index of microcirculatory resistance. Conclusions There was a high prevalence of visual‐functional mismatches between QCA and FFR. The discrepancy was related to clinical characteristics, lesion‐specific factors, and microvascular resistance that was undistinguishable by coronary angiography, thus suggesting the importance of physiological lesion assessment.

Effect of Elective Percutaneous Coronary Intervention on Hyperemic Absolute Coronary Blood Flow Volume and Microvascular Resistance

Background— The hemodynamics involved in the relationship between absolute coronary blood flow (ABF) volume and myocardial resistance (MR) are complex, and the effect of percutaneous coronary intervention (PCI) on their changes remains unclear. The aim of this study was to investigate the differences in hyperemic ABF and MR before and after elective PCI using a thermodilution method. Methods and Results— We investigated 28 vessels (right coronary artery, 9; left anterior descending coronary artery, 18; left circumflex coronary artery, 1) from 28 patients with stable angina pectoris undergoing elective PCI. ABF was measured pre- and post-PCI using a pressure–temperature sensor-equipped wire, based on a thermodilution method with a continuous saline infusion of 20 mL/min through a proximally located microcatheter with an end-hole in the target vessel. MR equals distal coronary perfusion pressure divided by ABF at maximal hyperemia. Conventional fractional flow reserve was also measured pre- and post-PCI. Fractional flow reserve increased significantly after PCI (from 0.70 [0.65–0.75] to 0.88 [0.85–0.95]) in all examined territories. ABF also increased significantly (from 137.8 mL/min [86.3–180.8 mL/min] to 173.3 mL/min [137.9–234.3 mL/min] ; increase: 52.8 mL/min [9.7–80.8 mL/min]) while MR decreased in 11 vessels and increased in 17. No significant relationship was detected between these increases in fractional flow reserve and ABF. Both pre- and post-PCI MR distributed in a wide range, and there was a significant relationship between pre-PCI MR and the increase in ABF (r=0.44; P=0.02) although no significant change in MR was observed between pre- and post-PCI (P=0.37). Conclusions— Direct measurement of ABF and MR using thermodilution method offers a feasible approach that could shed a light on previously unclear aspects of coronary hemodynamics.

Prevalence of Thin-Cap Fibroatheroma in Relation to the Severity of Anatomical and Physiological Stenosis

BACKGROUND The relationship between the features of morphologically unstable plaque and physiological lesion severity remains elusive. We aimed to investigate this relationship using optical coherence tomography (OCT)-derived high-risk plaque characteristics and fractional flow reserve (FFR) as the degree of anatomical and physiological stenosis severity.Methods and Results:We investigated 286 de novo intermediate and severe coronary lesions in 248 patients who underwent OCT and FFR examinations. Lesions were divided into tertiles based on either FFR or quantitative coronary angiographic diameter stenosis (QCA-%DS). The OCT findings were compared among the tertiles of FFR and QCA-%DS. FFR and QCA tertiles were defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74≤FFR≤0.81), and FFR-T3 (FFR >0.81); and QCA-T1 (%DS ≥61%), QCA-T2 (51%≤%DS<61%), and QCA-T3 (%DS <51%). The prevalence of thin-cap fibroatheroma (TCFA) was significantly greater in FFR-T1 (20.0%) than in FFR-T2 and FFR-T3 (7.0%, P=0.03 and 7.7%, P=0.04, respectively), although no significant differences were observed among the QCA tertiles. CONCLUSIONS Physiological severity of coronary stenosis evaluated by FFR correlated with plaque instability in terms of TCFA. Preferable clinical outcomes for lesions with negative FFR based on the existing clinical evidence might be attributable to less likelihood of TCFA.

Atrioventricular conduction disturbance during pulmonary vein isolation using the second-generation cryoballoon — Vagal impact of cryoballoon ablation

BACKGROUND Vagal reactions of the sinus node during pulmonary vein isolation (PVI) have been reported, however, data on intra-procedural atrioventricular conduction disturbances have been sparse. The present study aimed to investigate the clinical characteristics of atrioventricular conduction block (AVB) during PVI using second-generation cryoballoons. METHODS A total of 2252 PVs among 568 consecutive atrial fibrillation patients undergoing PVI with 28-mm cryoballoons were analyzed. In 44 patients, left superior PVs (LSPVs) were initially targeted (initial-LSPV-group). In the remaining 524 patients, LSPVs were targeted following right superior PVs (RSPVs) (initial-RSPV-group). RESULTS Marked sinus arrests/bradycardia occurred in 14 patients only in the initial-LSPV-group, and the incidence was significantly higher in the initial-LSPV than initial-RSPV-group (14/44 vs. 0/524, p < 0.001). Intra-procedural AVB with 3.6 [1.9-8.2] second maximal RR intervals appeared in 12 patients during freezing (n = 1) or after balloon deflation following freezing (n = 11). The targeted PVs were the LSPV, left common PV, right inferior PV, and RSPV in 8, 1, 2, and 1 patients, respectively. The incidence was similar between the initial-LSPV and initial-RSPV-groups (1/44 vs. 11/524, p = 0.938). Four patients exhibited complete AVB with more than a 6 s maximal RR interval. Three patients experienced AVB during atrial fibrillation. AVB was observed a median of 23.0 [15.0-70.0] seconds after balloon deflation and 76.0 [60.0-125.0] seconds after freezing termination. AVB persisted for 56.0 [36.0-110.0] seconds, and all recovered spontaneously with or without requiring back-up pacing. CONCLUSIONS A marked transient AV conduction disturbance could occur after balloon deflation, especially during LSPV ablation, regardless of the order of targeted PVs.

Silent cerebral events/lesions after second-generation cryoballoon ablation: How can we reduce the risk of silent strokes?

BACKGROUND Atrial fibrillation (AF) ablation is associated with a substantial risk of silent cerebral events/lesions (SCEs/SCLs) detected on magnetic resonance imaging (MRI). OBJECTIVE The purpose of this study was to investigate the factors associated with the incidence of SCEs/SCLs during second-generation cryoballoon ablation. METHODS Two hundred fifty-six AF patients underwent brain MRI 1 day after pulmonary vein (PV) isolation using second-generation cryoballoons with a single 28-mm balloon and short freeze strategy. RESULTS Overall, 991 of 1016 PVs (97.5%) were successfully isolated by 4.9 ± 1.3 cryoballoon applications per patient, and 25 PVs required touch-up radiofrequency ablation. The total procedure time was 72.7 ± 26.1 minutes. SCEs and SCLs were detected in 68 (26.5%) and 27 (10.5%) patients, respectively. None of the patients reported any neurologic symptoms. Reinsertion of once withdrawn cryoballoons and subsequent applications significantly increased the incidence of SCEs (odds ratio [OR] 2.057; 95% confidential interval [CI] 1.051-4.028; P = .035), and additional left atrial mapping with a multielectrode catheter significantly increased the incidence of SCLs (OR 3.317; 95% CI 1.365-8.056; P = .008). Transient coronary air embolisms were significantly associated with the incidence of SCLs (OR 3.447; 95% CI 1.015-11.702; P = 0.047). On the contrary, an uninterrupted anticoagulation regimen, use of radiofrequency deliveries for transseptal access, cryoballoon air removal with extracorporeal balloon inflations, strength of the MRI magnet, internal electrical cardioversion, and touch-up ablation were not associated with the incidence of SCEs/SCLs. CONCLUSION A significant number of SCE/SCL occurrences was observed after second-generation cryoballoon ablation procedures. These results suggest that air embolisms are the main mechanism of SCEs/SCLs, and the injected air volume might determine the lesion type.

Coronary physiological assessment combining fractional flow reserve and index of microcirculatory resistance in patients undergoing elective percutaneous coronary intervention with grey zone fractional flow reserve

The aim of this study is to investigate the association between fractional flow reserve (FFR) values and change in coronary physiological indices after elective percutaneous coronary intervention (PCI).

Association Between Prior Aspirin Use and Morphological Features of Culprit Lesions at First Presentation of Acute Coronary Syndrome Assessed by Optical Coherence Tomography

BACKGROUND The effect of prior use of aspirin (ASA) on the onset of acute coronary syndrome (ACS) has not been clarified. This study used optical coherence tomography (OCT) to investigate the morphological features of culprit lesions of ACS in patients with prior ASA use.Methods and Results:In total, 442 patients with their first ACS episode undergoing OCT for the culprit lesions were investigated. Clinical characteristics, OCT findings, and adverse events at 30 days were compared between patients with prior ASA use and ASA-naïve patients (non-ASA). 67 patients (15.2%) had received ASA at presentation. The ASA group was older, had higher frequency of dyslipidemia and hypertension, and lower renal function than the non-ASA group. Non-ST-elevation ACS was more prevalent in the ASA than in the non-ASA group (79.1 vs. 53.6%, P<0.001). Propensity score matching yielded 49 patients in both groups. OCT revealed less frequent thrombi in the ASA than in the non-ASA group in both the entire (37.3 vs. 75.2%, P<0.001) and score-matched cohorts (38.8 vs. 75.5%, P<0.001), whereas no significant difference was observed in plaque characteristics. Rate of adverse events did not differ between the ASA and the non-ASA groups in the matched cohort. CONCLUSIONS With a first ACS presentation, patients with prior ASA use were more likely to present with non-ST-elevation ACS with less frequent intraluminal thrombi, but no significant difference in underlying plaque characteristics or clinical course.

Characteristics of Phrenic Nerve Injury During Pulmonary Vein Isolation Using a 28‐mm Second‐Generation Cryoballoon and Short Freeze Strategy

Background The reported incidence of phrenic nerve injury (PNI) varies owing to different definitions, balloon generations, balloon size, freezing regimen, and protective maneuvers. We evaluated the incidence, predictors, and outcome of PNI during cryoballoon pulmonary vein isolation in a large population. Methods and Results Five hundred fifty atrial fibrillation patients underwent pulmonary vein isolation using one 28‐mm second‐generation cryoballoon and single 3‐minute freeze strategy under diaphragmatic compound motor action potential (CMAP) monitoring. A total of 34 (6.2%) patients experienced PNI during the right superior and inferior pulmonary vein ablation in 30 and 4 patients, respectively. Applications were interrupted using double‐stop techniques after 136 [104–158] second applications, and a pulmonary vein isolation was already achieved in all but one case. The baseline CMAP amplitude and timing of deflation (CMAP def) were 0.75±0.30 and 0.17±0.17 mV, respectively. Persistent atrial fibrillation, larger right superior pulmonary vein ostia, and deeper balloon positions were associated with higher incidences of PNI. The CMAP def predicted a PNI recovery delay, and the best cutoff value for predicting PNI recovery by the next day was 0.20 mV (sensitivity 57.1%, specificity 100%). Among 6 patients undergoing second procedures 8.5 (6.7–15.0) months later, the right superior pulmonary vein was durable in 3 with >120 second applications. Despite active balloon deflation, no significant pulmonary vein stenosis was observed in 15 right superior pulmonary veins evaluated 6 (5–9) months later. No patients had symptoms, and the PNI recovered 1 day and 1 month postprocedure in 21 and 4 patients, respectively. Conclusions PNI resulting from cryoballoon ablation was reversible. The double‐stop technique is safe, and immediate active deflation following a CMAP decrease appears to be essential for faster PNI recovery.

CLINICAL SIGNIFICANCE OF LIPID-RICH PLAQUE WITH INTACT FIBROUS CAP DEFINED BY OPTICAL COHERENCE TOMOGRAPHY IN ACUTE MYOCARDIAL INFARCTION

Lipid-rich plaque (LRP) is thought to be a precursor to cardiac events. Intact fibrous cap (IFC) has different underlying pathology in comparison with plaque rupture. Nevertheless, clinical significance of LRP with IFC in acute myocardial infarction (AMI) culprit lesions has not fully elucidated in