Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Atrial Tachycardia in the Coronary Sinus Communicating With Circumflex Artery Aneurysm.

Coronary artery fistula is a rare anomaly, and localized re-entrant atrial tachycardia (AT) in the coronary sinus (CS) has rarely been reported. We report a case in a patient with a left circumflex artery aneurysm associated with the CS fistula who underwent radiofrequency catheter ablation for localized re-entrant AT, which originated from the CS.

Efficacy of Native T1 Mapping for Patients With Non-Ischemic Cardiomyopathy and Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

BACKGROUND: We investigated the efficacy of left ventricular (LV) myocardial damage by native T1mapping obtained with cardiac magnetic resonance (CMR) for patients undergoing transcatheter edge-to-edge repair (TEER).Methods and Results: We studied 40 symptomatic non-ischemic heart failure (HF) patients and ventricular functional mitral regurgitation (VFMR) undergoing TEER. LV myocardial damage was defined as the native T1Z-score, which was converted from native T1values obtained with CMR. The primary endpoint was defined as HF rehospitalization or cardiovascular death over 12 months after TEER. Multivariable Cox proportional hazards analysis showed that the native T1Z-score was the only independent parameter associated with cardiovascular events (hazard ratio 3.40; 95% confidential interval 1.51-7.67), and that patients with native T1Z-scores <2.41 experienced significantly fewer cardiovascular events than those with native T1Z-scores ≥2.41 (P=0.001). Moreover, the combination of a native T1Z-score <2.41 and more severe VFMR (effective regurgitant orifice area [EROA] ≥0.30 cm2) was associated with fewer cardiovascular events than a native T1Z-score ≥2.41 and less severe VFMR (EROA <0.30 cm2; P=0.002). CONCLUSIONS: Assessment of baseline LV myocardial damage based on native T1Z-scores obtained with CMR without gadolinium-based contrast media is a valuable additional parameter for better management of HF patients and VFMR following TEER.

Cost-effective analysis of transcatheter aortic valve replacement in patients with severe symptomatic aortic stenosis: A prospective multicenter study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) does not benefit all patients. We performed a prospective multicenter study to investigate the cost-effectiveness of TAVR in a Japanese cohort. METHODS AND RESULTS: We prospectively enrolled 110 symptomatic patients with severe AS who underwent TAVR from five institutions. The quality of life measurement (QOL) was performed for each patient before and at 6 months after TAVR. Patients without an improvement in QOL at 6 months after TAVR were defined as non-responders. Pre-TAVR higher QOL, higher clinical frailty scale predicted the non-responders. Three models, 1) conservative treatment for all patients strategy, 2) TAVR for all patients strategy, and 3) TAVR for a selected patient strategy who is expected to be a responder, were simulated. Lifetime cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. In comparison to conservative therapy for all patients, ICER was estimated to be 5,765,800 yen/QALY for TAVR for all patients and 2,342,175 yen/QALY for TAVR for selected patient strategy patients, which is less than the commonly accepted ICER threshold of 5,000,000 yen/QALY. CONCLUSIONS: TAVR for selected patient strategy model is more cost-effective than TAVR for all patient strategy without reducing QOL in the Japanese healthcare system. TAVR for selected patient strategy has potential benefit for optimizing the TAVR treatment in patients with high frailty and may direct our resources toward beneficial interventions.

Rapidly progressive infective endocarditis after MitraClip therapy: A rare complication of transcatheter edge-to-edge mitral valve repair.

Infective endocarditis (IE) is a rare, life-threatening complication of MitraClip (Abbott, Abbott Park, IL, USA) therapy. We report a case of an 84-year-old male who underwent transcatheter edge-to-edge mitral valve (MV) repair using MitraClip (Abbott, Abbott Park, IL, USA) 4 weeks prior for ventricular functional mitral regurgitation (MR) and returned with unstable hemodynamics and high-grade fever. Transthoracic echocardiography (TTE) on emergency admission showed thickening of the anterior mitral leaflet (AML) without apparent MR deterioration. TTE and transesophageal echocardiography (TEE) performed the next day showed severe MR due to rapidly progressing AML degeneration with aneurysmal formation. During the TEE examination, exacerbated heart failure due to severe MR caused cardiogenic shock and subsequent ventricular fibrillation, necessitating emergency extracorporeal cardiopulmonary resuscitation. Considering the positive findings of methicillin-resistant Staphylococcus aureus (MRSA) in blood cultures and degenerative MV findings, MitraClip-related IE was diagnosed; finally, MV replacement was performed. Retrospective consideration suggested that the potential causes of this MitraClip-related IE were valve injuries caused by multiple full-close procedures and insufficient prophylaxis for preoperatively detected MRSA. MitraClip-related IE has destructive characteristics that necessitate surgical intervention despite high risks; therefore, we should prevent procedure-related MV injuries and implement preoperative infection precautions to prevent catastrophic complications, particularly in patients with preoperative nasal MRSA-positive findings. Learning objectives: MitraClip-related infective endocarditis (IE) is a rare but fatal condition. IE caused by methicillin-resistant Staphylococcus aureus (MRSA), in particular, has an inferior prognosis with high mortality rates due to its destructive nature. Therefore, interventionalists should consider preventive strategies to avoid procedure-related valve injuries and adequately prepare for prophylaxis of patients who are carriers of MRSA to prevent MitraClip-related IE caused by MRSA.

Association of Left Atrial Size With Stroke or Systemic Embolism in Patients With Atrial Fibrillation Having Undergone Bioprosthetic Valve Replacement From the BPV-AF Registry.

Background: The left atrial volume index (LAVI) is important for predicting thromboembolism in patients with non-valvular atrial fibrillation (AF), but the utility of LAVI for predicting thromboembolism in patients with both bioprosthetic valve replacement and AF remains unclear. Methods and Results: Of 894 patients from a previous multicenter prospective observational registry (BPV-AF Registry), 533 whose LAVI data had been obtained by transthoracic echocardiography were included in this subanalysis. Patients were divided into tertiles (T1-T3) according to LAVI as follows: T1 (n=177), LAVI=21.5-55.3 mL/m2; T2 (n=178), LAVI=55.6-82.1 mL/m2; T3 (n=178), LAVI=82.5-408.0 mL/m2. The primary outcome was defined as either stroke or systemic embolism for a mean (±SD) follow-up period of 15.3±4.2 months. Kaplan-Meier curves indicated that the primary outcome tended to occur more frequently in the group with the larger LAVI (log-rank P=0.098). Comparison of T1 with T2 plus T3 using Kaplan-Meier curves indicated that patients in T1 experienced significantly fewer primary outcomes (log-rank P=0.028). Furthermore, univariate Cox proportional hazard regression showed that 1.3- and 3.3-fold more primary outcomes occurred in T2 and T3, respectively, than in T1. Conclusions: Larger LAVI was associated with stroke or systemic embolism in patients who had undergone bioprosthetic valve replacement and with a definitive diagnosis of AF.

Acute Coronary Syndrome Due to Intraplaque Hemorrhage in a Post-gastrectomy Patient with a Latent Severe Glycemic Disorder.

Glycemic disorders involving large glucose fluctuations and recurrent hypoglycemia may lead to adverse cardiovascular events, including acute coronary syndrome (ACS). Flash glucose monitoring (FGM) has reportedly been useful for detecting latent glycemic disorders. However, only a few studies have so far reported latent glycemic disorders in coronary artery disease. Thus, we herein present a unique case of ACS due to intraplaque hemorrhage in a post-gastrectomy patient who had no apparent coronary risk, except for a latent severe glycemic disorder detected via FGM. This masked etiology should be considered in ACS patients who have no apparent cardiovascular risks in order to improve their cardiovascular outcomes.

Stentless percutaneous coronary intervention with directional coronary atherectomy and drug-coated balloon angioplasty in worsening angina patients with metal allergies.

Metal allergy is a concern in percutaneous coronary intervention (PCI) with stent implantation because of its potential association with poor cardiovascular outcomes, such as stent thrombosis and recurrent in-stent restenosis requiring revascularization. Although stentless PCI with drug-coated balloon (DCB) angioplasty is theoretically useful for patients with metal allergies, DCB angioplasty alone for huge plaques in large vessels may yield inadequate luminal enlargement and coronary deep dissection, leading to insufficient results. Directional coronary atherectomy (DCA) is effective to reduce plaque volume. However, the efficacy of DCA followed by DCB (DCA/DCB) angioplasty in patients with metal allergies has never been described. We present two cases wherein stentless PCI with DCA/DCB angioplasty was an alternative revascularization strategy for patients with metal allergy and concomitant worsening angina pectoris involving proximal left anterior descending artery stenoses. Preoperative evaluation using coronary computed tomography angiography in Case 1 and intravascular ultrasound in Case 2 was useful to determine the possible use of the DCA/DCB procedure for huge plaques in large vessels. Learning objective: Revascularization for patients with metal allergy with worsening angina pectoris due to stenoses of the proximal main arteries is often challenging because of the necessity to avoid stent implantation. As stentless percutaneous coronary intervention (PCI) is theoretically useful in such settings, PCI with directional coronary atherectomy (DCA)/drug-coated balloon angioplasty can be one of the treatable strategies. Preoperative evaluation of plaque morphology for the suitability of DCA procedure is important.

Rare complications of Guideplus guide-extension catheter during complex percutaneous coronary intervention.

Guide-extension catheters (GECs) are effective in providing reinforced backup support and coaxial alignment, leading to successful complex percutaneous coronary intervention (PCI). However, several GEC-associated complications have been reported, including coronary injuries, thrombotic events, and GEC fractures. The Guideplus GEC (Guideplus II ST; Nipro, Osaka, Japan) has a higher crossability due to its unique hydrophilic-coated soft cylinder, which is frequently used in complex PCI for diffuse, tortuous, and heavily calcified lesions. We describe two cases of Guideplus GEC-associated complications during complex PCI: Case 1 with a radiopaque marker dislodgement and Case 2 with a stent dislodgment. In both cases, the Guideplus GEC was used within 7-Fr guiding catheters, employing the mother-and-child technique. A large inner-catheter gap between these catheters caused by a positioning bias due to arterial bends (the aortic arch in Case 1 and brachiocephalic arterial bends in Case 2) may have caused these complications due to its interference with coronary devices (the trapping balloon in Case 1, and the scoring balloon in Case 2). Early cognition and management of these potential Guideplus GEC-associated complications are important to prevent further deterioration. Learning objectives: The Guideplus guide-extension catheter (GEC) with a hydrophilic-coated soft cylinder can deliver coronary devices to complex lesions owing to its high crossability. However, delivering coronary devices with the Guideplus GEC should be carefully performed because a large inner-catheter gap between Guideplus GEC and a guiding catheter may occur if a proximal port of the Guideplus GEC is located at an arterial bend. In such settings, Guideplus GEC-associated complications must be carefully observed, including radiopaque marker dislodgement and stent dislodgement.

Comparison of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and an Aortic Bioprosthetic Valve.

BACKGROUND: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited data comparing DOACs and warfarin in AF patients with an aortic BPV.Methods and Results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51-1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577). CONCLUSIONS: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.

Torsade de pointes in an older patient with Takotsubo cardiomyopathy caused by licorice-induced pseudoaldosteronism: A case report.

Takotsubo cardiomyopathy (TCM) causes QT interval prolongation, potentially leading to a fatal arrhythmia. We report the first case of TCM associated with licorice-induced pseudoaldosteronism causing fatal arrhythmia in an older patient on polypharmacy including yokukansan (TJ-54) and galantamine. Polypharmacy should be resolved to prevent unexpected adverse events in older patients.

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.