Diagnostic Accuracy of Pre-Transcatheter Aortic Valve Replacement Nitroglycerin-Free Fractional Flow Reserve-Computed Tomography-Based Physiological Assessment in Patients With Severe Aortic Stenosis for Predicting Post-Transcatheter Aortic Valve Replacement Ischemia.

BACKGROUND: Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. CONCLUSIONS: FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

Narrow QRS Complex Tachycardia With Variable R-R Intervals and Discrete P Waves.

Irregular narrow QRS complex tachycardia is associated with a wide range of differential diagnoses, including atrial fibrillation and atrial tachyarrhythmia with altered atrioventricular conduction. Here, we present a case of narrow QRS complex tachycardia with variable R-R intervals and discrete P waves. (Level of Difficulty: Intermediate.).

Multidisciplinary diagnostic approach for fulminant myocarditis related to coronavirus disease 2019 messenger RNA vaccines: a case report.

Background: Recent reports have raised serious concerns regarding acute myocarditis related to coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. There are only a few reports of fulminant lymphocytic myocarditis that developed after vaccination. Although the diagnostic approach varied among them, no cases with multidisciplinary diagnostic approaches, including cytokine analysis, have been reported. Case summary: A 59-year-old male with no medical history complained of chest pain a day after receiving the first dose of COVID-19 mRNA (BNT162b2) vaccination. On hospital Day 3, he developed a refractory cardiogenic shock and pulseless ventricular tachycardia, requiring mechanical circulatory support secondary to an exacerbation of myocarditis. Based on the clinical course and examination results, including histologic findings showing a diffuse lymphocytic inflammatory infiltrate with abundant T cells and macrophages in the myocardium, and cardiac magnetic resonance (CMR) findings showing a high-intensity signal on the T2-weighted image and late gadolinium enhancement, he was diagnosed with fulminant myocarditis related to COVID-19 mRNA vaccination. His haemodynamic status gradually improved without immunosuppressive or anti-inflammatory therapy, and he was discharged from hospital on Day 47. To investigate the pathogenesis, we performed cytokine analysis, which showed an increase in serum IP-10, MCP-3, and MIG concentrations, suggesting that Th1-type chemokines preferentially promote cellular immunity. Discussion: In the present case of a patient with fulminant myocarditis following COVID-19 mRNA vaccination diagnosed through histopathological and CMR findings, additional cytokine analysis revealed that elevated levels of cytokines pertaining to Th1 immune response may be involved in disease pathogenesis. A multidisciplinary diagnostic approach is crucial not only to comprehend an individual patient's condition but also to clarify the disease pathogenesis.

Prognostic Value of Left Atrial Calcification After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Left atrial calcification (LAC) has occasionally been observed in patients who underwent catheter ablation for atrial fibrillation (AF) by chest computed tomography (CT). However, the evidence regarding the clinical impact of LAC in patients with AF is lacking. OBJECTIVES: This study aims to investigate the prevalence of LAC in AF patients and evaluate its clinical significance after AF ablation. METHODS: This observational registry included AF patients who received computed tomography and serial transthoracic echocardiography between January 2010 and November 2017. The primary composite outcome included cardiovascular death, hospitalization for worsening heart failure, and ischemic stroke. RESULTS: Among 534 patients (age 72 ± 13 years, 62.5% men) who met the inclusion criteria, 31 (5.8%) had LAC. In multivariable analysis, AF ablation was associated with an 11.8-fold (OR: 11.8; 95% CI: 2.03-227.65) increased risk of the development of LAC in AF patients. Among 218 patients with AF ablation, LAC was detected in 30 (13.8%) patients. Prior stroke (HR: 2.73; 95% CI: 1.08-6.93) and multiple ablation procedures (HR: 4.21; 95% CI: 1.63-10.87) were independently associated with the development of LAC in AF-ablation patients. During a median follow-up of 5.8 years, the primary composite outcome occurred in 11 patients in the LAC group (39.8 per 1,000 person-years) and 10 patients in the non-LAC group (8.9 per 1,000 person-years). The adjusted HR for the primary composite outcome in the LAC group, as compared with the non-LAC group, was 2.81 (95% CI: 1.16-6.84; P = 0.02). CONCLUSIONS: The presence of LAC was a significant and independent prognostic factor for identifying major adverse cardiovascular events after AF ablation.

Potential relationship between high wall shear stress and plaque rupture causing acute coronary syndrome.

The relationship between high wall shear stress (WSS) and plaque rupture (PR) in longitudinal and circumferential locations remains uncertain. Overall, 100 acute coronary syndrome patients whose culprit lesions had PR, documented by optical coherence tomography (OCT), were enrolled. Lesion-specific three-dimensional coronary artery models were created using OCT data. WSS was computed with computational fluid dynamics analysis. PR was classified into upstream-PR, minimum lumen area-PR, and downstream-PR according to the PR's longitudinal location, and into central-PR and lateral-PR according to the disrupted fibrous cap circumferential location. In the longitudinal 3-mm segmental analysis, multivariate analysis demonstrated that higher WSS in the upstream segment was independently associated with upstream-PR, and thinner fibrous cap was independently associated with downstream-PR. In the PR cross-sections, the PR region had a significantly higher average WSS than non-PR region. In the cross-sectional analysis, the in-lesion peak WSS was frequently observed in the lateral (66.7%) and central regions (70%) in lateral-PR and central-PR, respectively. Multivariate analysis demonstrated that the presence of in-lesion peak WSS at the lateral region, thinner broken fibrous cap, and larger lumen area were independently associated with lateral-PR, while the presence of in-lesion peak WSS at the central region and thicker broken fibrous cap were independently associated with central-PR. In conclusion, OCT-based WSS simulation revealed that high WSS might be related to the longitudinal and circumferential locations of PR.

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome.

BACKGROUND: Optical coherence tomography-derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain. OBJECTIVES: This study sought to investigate the relationship between post-percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS). METHODS: This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI. RESULTS: Among 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF. CONCLUSIONS: Vessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858).

Real-world clinical outcomes of percutaneous transluminal septal myocardial ablation for patients with drug-refractory hypertrophic obstructive cardiomyopathy: results from a retrospective multicenter registry of non-high-volume centers.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a well-established interventional therapy for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) as an alternative to surgical myectomy. Although guidelines recommend that PTSMA should be performed in institutions with extensive experience, it is not centralized to such high-volume centers in real-world clinical practice. Thus, this study aimed to assess the feasibility of PTSMA in non-high-volume centers. We retrospectively examined patients with HOCM who underwent PTSMA between August 2012 and May 2020 at four institutions that experienced fewer than 20 cases of PTSMA procedures. The primary clinical endpoint was a composite of safety (all-cause death, electrical defibrillation for ventricular tachycardia or fibrillation, cardiac tamponade, permanent pacemaker implantation, and repeated interventions) and efficacy endpoints (repeated interventions [PTSMA or surgical myectomy]). Fifty-eight consecutive patients were enrolled. During the 30-day follow-up, no major clinical adverse events were noted except three patients (5.2%) requiring permanent pacemaker implantation for complete atrioventricular block. The percentage of patients with New York Heart Association functional class 1 or 2 significantly increased from 8.6 to 100% (p < 0.001). In the Cox proportional hazard model, left ventricular outflow tract pressure gradient at rest ≥ 30 mmHg (hazard ratio [HR] 6.56; 95% confidence interval [CI] 1.44-29.90; p = 0.015) and mitral regurgitation grade ≥ 3 (HR 10.75; 95% CI 1.81-63.79; p = 0.009) at the 30-day follow-up were associated with a composite of major clinical adverse events. The current study demonstrated that 58 patients who underwent PTSMA in non-high-volume centers had favorable 30-day clinical outcomes, with a primary composite endpoint rate of 5.2%. A prospective study with a larger sample size and longer follow-up is warranted to verify the safety and efficacy of PTSMA in non-high-volume centers.

Cholesterol uptake capacity: A new measure of high-density lipoprotein functionality as a predictor of subsequent revascularization in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) functionality is an important determinant of coronary artery disease (CAD) development. We recently developed cholesterol-uptake capacity (CUC), a rapid cell-free assay system that directly evaluates the capacity of HDL to accept additional cholesterol. We aimed to evaluate the association between CUC and revascularization in patients who have undergone percutaneous coronary intervention (PCI). METHODS: We retrospectively reviewed patients who underwent PCI with subsequent revascularization or coronary angiography (CAG) without revascularization. The patients who had frozen blood samples for which CUC were measurable at the index PCI and follow-up were enrolled. RESULTS: We finally enrolled 74 patients who underwent subsequent revascularization and 183 patients who underwent follow-up CAG without revascularization. The serum CUC level at the index PCI was significantly lower in the revascularization group than that in the non-revascularization group (84.3 [75.2-98.9] vs. 92.0 [81.6-103.3 A U.]; p = 0.004). Multivariate logistic regression analysis revealed that decreased serum CUC level at the index PCI was independently associated with subsequent revascularization (odds ratio, 0.98; 95% confidence interval, 0.969-1.000). After adjusting for 16 cardiovascular risk factors, the serum CUC level at the index PCI and follow-up and the absolute change in serum CUC level from the index PCI to follow-up were significantly lower in the revascularization group than those in the non-revascularization group. CONCLUSIONS: Serum CUC level at index PCI was independently associated with subsequent revascularization after PCI. Continuous assessment of HDL functionality by CUC might help predict subsequent revascularization after PCI.

Anatomical evaluation of the esophagus using computed tomography to predict acute gastroparesis following atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation is an effective treatment; however, periesophageal vagal nerve injury is not rare and sometimes results in acute gastroparesis (AGP) after atrial fibrillation ablation (AFA). We sought to investigate the incidence and risk factors of AGP via preprocedural computed tomography (CT) analysis. METHODS: We retrospectively reviewed 422 patients who underwent index AFA at our center. Using contrast-enhanced CT performed before ablation, the anatomical characteristics of the esophagus were compared between patients with and without post-ablation AGP. AGP was diagnosed by the presence of symptoms, fasting abdominal X-ray radiography as a screening test, and additional abdominal imaging. RESULTS: Of the 422 patients (age, 67 ± 11 years; male, 68.5%; cryoballoon, 63.7%), AGP developed in 14 (3.3%) patients, and six of 14 patients were asymptomatic. AGP resolved in all patients within 4 weeks without invasive treatment. In the AGP group, the esophagus was frequently located on the vertebra (middle-positioned esophagus) (AGP vs non-AGP, 42.9% vs 11.5%; P = .01), and additional posterior wall ablation was frequently performed (50.0% vs 14.5%; P = .02). In the multivariate analysis, middle-positioned esophagus (P = .02; odds ratio, 9.0; 95% confidence interval [CI], 1.5-53.3) and additional posterior wall ablation (P = .01; odds ratio, 7.6; 95% CI, 1.5-42.1) were independent predictors of AGP. CONCLUSIONS: Anatomical evaluation of the esophagus using CT may be simple and useful for predicting AGP after AFA. High-risk patients who have middle-positioned esophagus or who underwent excessive posterior wall ablation should be followed up closely.

Association Between Visit-to-Visit Variability in Low-Density Lipoprotein Cholesterol and Plaque Rupture That Leads to Acute Coronary Syndrome.

Background: The effect of intraindividual variability in lipid levels on the onset of acute coronary syndrome (ACS) remains uncertain. We evaluated the relationship between intraindividual variability in lipid levels and culprit lesion morphologies by optical coherence tomography (OCT). Methods and Results: Seventy-four consecutive patients with ACS whose cholesterol levels were assessed ≥3 times during outpatient visits before the onset of ACS were enrolled in the study; 222 patients without significant stenotic lesions were used as a control group. Based on OCT findings of culprit lesions, ACS patients were categorized into a plaque rupture ACS (PR-ACS) group (n=44) or a non-plaque rupture ACS (NPR-ACS) group (erosion or calcified nodule; n=30). Visit-to-visit variability in lipid levels was evaluated using the corrected variability independent of the mean (cVIM). Patients with ACS had significantly higher low-density lipoprotein cholesterol (LDL-C) levels and cVIM in LDL-C than the control group. The PR-ACS group had significantly higher mean LDL-C levels and greater cVIM in LDL-C than the control group. The PR-ACS group had a significantly higher cVIM than the NPR-ACS group, despite similar mean LDL-C levels. Multivariate analysis revealed that higher cVIM of LDL-C was an independent predictor of PR-ACS (odds ratio 1.06; P=0.018). Conclusions: In addition to the LDL-C level, greater visit-to-visit variability in LDL-C levels may be associated with the onset of ACS induced by plaque rupture.

Morphological Plaque Characteristics and Clinical Outcomes in Patients With Acute Coronary Syndrome and a Cancer History.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography-guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P<0.001). Cancer history was independently associated with nonplaque rupture (plaque erosion or calcified nodule) in ACS culprit lesions (odds ratio, 4.00; P<0.001). Cancer history was independently associated with major adverse cardiovascular events (hazard ratio [HR], 1.98; P=0.002). Nonplaque rupture in ACS culprit lesions was independently associated with major adverse cardiovascular events (HR, 1.60; P=0.011). Conclusions Patients with a cancer history had significantly worse clinical outcomes after ACS than those without a cancer history. Those with a cancer history had significantly higher plaque erosion and calcified nodule incidences in the ACS culprit lesions, which might partly explain their worse clinical outcomes. Registration URL: www.umin.ac.jp/ctr/index.htm. Unique Identifier: UMIN000038442.

Relationship among clinical characteristics, morphological culprit plaque features, and long-term prognosis in patients with acute coronary syndrome.

Culprit lesions of acute coronary syndrome (ACS) could be classified as plaque rupture (PR), erosion, or calcified nodule (CN). We aimed to determine the relationship among clinical characteristics, morphological plaque features, and long-term prognosis in ACS. Patients with ACS, who underwent pre-intervention optical coherence tomography between April 2013 and July 2018 were retrospectively enrolled, and classified into the three groups based on the culprit lesion morphology. In the 436 patients enrolled, incidences of PR, erosion, and CN in ACS culprit lesions were 46.1, 39.9, and 14.0%, respectively. Plaque erosion was more frequent in men aged < 60 years and CN was more frequent in older adults in both sexes (≥ 80 years) (P < 0.001). Patients with CN had a higher incidence of hemodialysis treatment (P < 0.001) and diabetes (P = 0.003). Multivariate analysis revealed that ST elevation myocardial infarction (STEMI) (P = 0.049) and presence of thin-cap fibroatheroma (TCFA) at the culprit lesion were independently associated with PR; in younger patients (< 60 year), preserved left ventricular ejection fraction and lower incidence of TCFA were correlated with plaque erosion; and older age, non-STEMI, or unstable angina pectoris, higher serum brain natriuretic peptide levels, and lower incidence of TCFA were independently associated with CN. Multivariable analysis revealed that CN (odds ratio [OR] 1.990, P = 0.005), male sex (OR 2.012, P = 0.004), and older age (OR 1.036, P < 0.001) were independently associated with future adverse events during a median follow-up of 757 days. Different patient characteristics and morphological features were associated with the type of culprit lesion in patients with ACS.

Prediction of the debulking effect of rotational atherectomy using optical frequency domain imaging.

Whether predicting the rotational atherectomy (RA) effect based on the position of optical frequency domain imaging (OFDI) is accurate remains uncertain. The aim of this study was to evaluate the predictive accuracy of OFDI in identifying RA location and area. Twenty-five patients who underwent RA with OFDI were included. On pre-RA OFDI images, a circle with the dimension of a Rota burr was drawn at the center of the OFDI catheter. The area where the circle overlapped with the vessel wall was defined as the predicted ablation area (P-area), and the actual ablated area (A-area) was measured. The predictive accuracy of OFDI was evaluated as follows: overlapped ablation area (O-area: overlapping P- and A-areas) divided by P-area = %Correct-area, and A-area - O-area divided by A-area = %Error-area. Cross-sections were separated into four categories based on the median values of %Correct- and %Error-area. Among 334 cross-sections, RA effects were confirmed in the predicted location in 87% of them. The median %Correct- and %Error-areas were 43.1% and 64.2%, respectively. Floppy wire, narrow lumen area, OFDI catheter close to the intima, and large arc of calcium were independently associated with good prediction (high %Correct-/low %Error-areas). Non-left anterior descending lesions, OFDI catheter far from the wire, and OFDI catheter and wire far from the intima were associated with irrelevant ablation (low %Correct-/ high %Error-areas). The accuracy of the OFDI-based predictions for RA effects was acceptable with regard to location, but not high with regard to area. Wire types, target vessels, and OFDI catheter and wire positions are important determinants for accurately predicting RA effect using pre-procedural OFDI.

Bidirectional atrioventricular reentrant tachycardia using bilateral accessory pathways.

Patients with Wolff-Parkinson-White (WPW) syndrome rarely have multiple accessory pathways (APs). Here, we present a case of a 21-year-old man with the manifest type B WPW syndrome who was experiencing multiple attacks of palpitations. The electrophysiological study revealed two APs located bilaterally: the anterolateral tricuspid annulus and lateral mitral annulus. Atrial/ventricular extrastimulations induced two types of wide QRS tachycardia conducting via two APs in the clockwise and counterclockwise direction. These two APs were eliminated with careful mapping and catheter ablation. .

Responsiveness to bepridil predicts atrial substrate in patients with persistent atrial fibrillation.

BACKGROUND: The low voltage zone (LVZ) detected with three-dimensional electroanatomical mapping is a surrogate marker of atrial scar in patients with persistent atrial fibrillation (PeAF) and is associated with poor clinical outcomes after catheter ablation. However, fewer studies have reported the relationship between responsiveness to antiarrhythmic drugs and the LVZ. METHODS: We retrospectively analyzed 76 patients who underwent catheter ablation for PeAF at our center. Rhythm control with bepridil was initiated before ablation in all patients, and electrical cardioversion was performed in cases of failure to restore sinus rhythm with bepridil alone. Patients with successful sinus restoration with bepridil alone (≤200 mg/d) were defined as "responders", while those who required electrical cardioversion as well were defined as "non-responders". We compared the LVZ ratio (ratio of the LVZ surface area to the left atrium surface area on three-dimensional electroanatomical mapping) and the recurrence-free rate after ablation between the two groups. RESULTS: Of the 76 patients, 48 (63.2%) were responders to bepridil. The median LVZ ratio was significantly lower in the responder group than in the nonresponder group (7.5% vs 14.0%, P = .009). Multivariate analysis revealed that response to bepridil was an independent predictor of normal voltage (P = .02, odds ratio = 0.20, 95% confidence interval = 0.04-0.76). The recurrence-free rate at 1 year after catheter ablation was significantly higher in the responder group than in the nonresponder group (87.1% vs 62.3%, P = .03). CONCLUSIONS: Response to bepridil is a marker of normal voltage in electroanatomical mapping and is significantly associated with better clinical outcomes after catheter ablation.

Feasibility of morphological assessment of coronary artery calcification with electrocardiography-gated non-contrast computed tomography: a comparative study with optical coherence tomography.

To investigate the feasibility of pre-procedural morphological assessment of coronary artery calcification in severely calcified lesions with electrocardiography (ECG)-gated non-contrast computed tomography (CT). Severely calcified coronary arteries in patients who underwent ECG-gated non-contrast CT prior to optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) were studied retrospectively. CT and OCT data were co-registered by marking landmark structures such as side branches and reviewed side by side with cross-sectional images. The maximum calcium angle (MCA) and presence of nodular calcification (NC) were evaluated. A total of 496 cross-sections in 16 lesions were included in this analysis. The Pearson correlation coefficient between CT- and OCT-derived MCA was 0.92 (p < 0.001). Bland-Altman plots of OCT-derived MCA in relation to CT-derived MCA showed a mean bias of 4.8 degrees with 95% limits of agreement of - 69.7 to 79.4 degrees. Sensitivity, specificity, and positive and negative predictive values of CT in identifying MCA > 270 degrees were 90.3%, 79.7%, 92.1%, and 97.4%, respectively. Sensitivity, specificity, and positive and negative predictive values of CT in identifying NC were 73.3%, 97.5%, 47.8%, and 99.2%, respectively. ECG-gated non-contrast coronary CT might be helpful to obtain detailed information of severe coronary artery calcification before PCI.