Optical frequency domain imaging-guided versus intravascular ultrasound-guided percutaneous coronary intervention for acute coronary syndromes: the OPINION ACS randomised trial.

BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).

Lipid profile and risk factors for neoatherosclerosis after drug-eluting stent implantation in acute coronary syndrome.

BACKGROUND: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. OBJECTIVE: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. METHODS: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. RESULTS: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). CONCLUSION: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

Hemodynamic effect of supra-annular implantation of SAPIEN 3 balloon expandable valve.

The hemodynamic impact of the implantation depth for balloon-expandable valves is under-investigated, especially with higher implantation techniques. We assessed the hemodynamic performance of supra-annular SAPIEN 3 valve implantation. This retrospective study involved consecutive patients who underwent transcatheter aortic valve replacement (TAVR) using the SAPIEN 3. The device implantation depth and transcatheter heart valve (THV) leaflet-nadir position were angiographically analyzed, and supra-annular implantation was defined as a higher leaflet-nadir position than the original annular line. The Doppler hemodynamic status was evaluated at patient discharge. Among 184 patients, 120 (65%) underwent supra-annular implantation, and their mean implantation depth was significantly lower than that of intra-annular implantation (1.1 vs. 5.2 mm, p < 0.001). No patients developed valve embolization or coronary occlusion, and none required the TAV-in-TAV procedure. Two (1.6%) patients in the supra-annular implantation group had a mild or greater paravalvular leak. Echocardiography demonstrated that supra-annular implantation had better hemodynamic performance, showing a larger indexed effective orifice area (iEOA) compared with intra-annular implantation (1.09 vs. 0.97 cm2/m2, p < 0.01). There was a weak but negative correlation between the implantation depth and iEOA (r = - 0.27, p < 0.01). Moderate or severe prosthesis-patient mismatch (PPM) was found in 35.9% of the intra-annular group and 9.2% of supra-annular of the supra-annular group (p < 0.01). In the multivariable analysis, supra-annular implantation was an independent predictor of better THV function (iEOA > 0.85). Supra-annular SAPIEN 3 implantation provides beneficial hemodynamic effects and reduces the PPM risk.

Pathological evaluation of predictors for delayed endothelial coverage after currently available drug-eluting stent implantation in coronary arteries: Impact of lesions with acute and chronic coronary syndromes.

BACKGROUND: The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking-a gap addressed in the current study. METHODS: From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis. RESULTS: Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; P = .02, 7.7% vs. 30.4%; P = .02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; P < .01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days (odds ratio [OR], 0.009; 95% confidence interval [CI], 0.006-0.012; P < .01), superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; P < .01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; P = .039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; P < .01) as delayed endothelial coverage predictors. CONCLUSIONS: Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.

How Electrical Storms Recur Over Time in Patients With Implantable Cardioverter Defibrillators　- Subanalysis of the Nippon Storm Study.

BACKGROUND: Electrical storms (E-storms), defined as multiple fatal ventricular arrhythmias over a short period, negatively affect the prognosis of patients receiving an implantable cardioverter defibrillator or cardiac resynchronization therapy with a defibrillator (ICD/CRT-D). However, the prognostic impact of recurrent E-storms has not been well elucidated. METHODS AND RESULTS: We analyzed the association between E-storm recurrences and mortality using data from 1,274 participants in the Nippon Storm Study, a prospective observational study conducted at 48 ICD/CRT-D centers in Japan. Differences in E-storm recurrences by patient characteristics were evaluated using the mean cumulative function (MCF), which is the cumulative number of E-storm episodes per patient as a function of time. Patients with multiple E-storms had a 3.39-fold higher mortality risk than those without E-storms (95% confidence interval 1.82-6.28; P<0.01). However, there was no significant difference in mortality risk between patients with a single E-storm and those without E-storms. The MCF curve exhibited a slower ascent in patients who received primary prevention ICD/CRT-D than in those who received secondary prevention ICD/CRT-D. However, when analyzing only patients with E-storms, the MCF curves demonstrated comparable trajectories in both groups. CONCLUSIONS: E-storm recurrences may have a negative impact on prognosis. Once patients with primary prevention experience an E-storm episode, they face a similar risk of subsequent recurrent E-storms as patients with secondary prevention.

Effectiveness of directional coronary atherectomy in treating recurrent in-stent restenosis: a case report.

Background: In-stent restenosis (ISR) remains a significant clinical problem. It is estimated that 10-20% of patients who develop a first event of ISR will develop recurrent ISR (R-ISR). However, the pathology of R-ISR remains largely unknown, and recommendations for its optimal management are lacking. In this case report, we discuss the effectiveness of directional coronary atherectomy (DCA) as an atherectomy device and the mechanism of R-ISR based on pathological findings obtained from DCA. Case summary: We report the case of a 62-year-old man with a history of ST-segment elevation myocardial infarction treated with percutaneous coronary intervention (PCI) to the mid left circumflex artery using a bare metal stent. Even after the introduction of adequate secondary prevention therapy for ISR, the patient underwent a total of six PCI sessions over 10 years following primary PCI for R-ISR. Eventually, the decision was made to institute treatment with DCA and a drug-coated balloon. No symptoms of restenosis were observed over the following 4 years. Discussion: In this case report, we demonstrate the effectiveness of DCA treatment for debulking a wide range of collagen-rich plaques and show that DCA treatment should be considered for the treatment of R-ISR.

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

BACKGROUND AND AIMS: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. RESULTS: Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92). CONCLUSIONS: Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES.

Bereaved family members' perspectives on quality of death in deceased acute cardiovascular disease patients compared with cancer patients - a comparison of the J-HOPE3 study and the quality of palliative care in heart disease (Q-PACH) study.

BACKGROUND: Outcome measures during acute cardiovascular disease (CVD) phases, such as quality of death, have not been thoroughly evaluated. This is the first study that compared the family members' perceptions of quality of death in deceased CVD patients and in deceased cancer patients using a bereaved family survey. METHODS: Retrospectively sent questionnaire to consecutive family members of deceased patients with CVD from ten tertiary hospitals from October 2017 to August 2018. We used the short version of the Good Death Inventory (GDI) and assessed overall care satisfaction. Referencing the GDI, the quality of death was compared between CVD patients admitted to a non-palliative care unit (non-PCU) and cancer patients in palliative care units (PCU) and non-PCUs in the Japan Hospice and Palliative Care Evaluation Study (J-HOPE Study). Additionally, in the adjusted analysis, multivariable linear regression was performed for total GDI score adjusted by the patient and participant characteristics to estimate the difference between CVD and other patients. RESULTS: Of the 243 bereaved family responses in agreement (response rate: 58.7%) for CVD patients, deceased patients comprised 133 (54.7%) men who were 80.2 ± 12.2 years old on admission. The GDI score among CVD patients (75.0 ± 15.7) was lower (worse) than that of cancer patients in the PCUs (80.2 ± 14.3), but higher than in non-PCUs (74.4 ± 15.2). After adjustment, the total GDI score for CVD patients was 7.10 points lower [95% CI: 5.22-8.97] than for cancer patients in PCUs and showed no significant differences compared with those in non-PCUs (estimates, 1.62; 95% CI [-0.46 to 5.22]). CONCLUSIONS: The quality of death perceived by bereaved family members among deceased acute CVD patients did not differ significantly from that of deceased cancer patients in general wards, however, was significantly lower than that of deceased cancer patients admitted in PCUs.

Clip opening while locked after transcatheter edge-to-edge mitral valve repair with different onset times: a case series.

Background: Transcatheter edge-to-edge mitral valve repair is now available in many countries and has achieved favourable therapeutic outcomes. However, there have been no reported cases of clip opening while locked (COWL) during the acute phase using the MitraClip G4 system (Abbott, Abbott Park, IL, USA). Case summary: We present two cases of COWL occurring at different phases: one immediately after clip release and the other 2 days post-procedure. In both cases, the initial treatment involved the use of the XTW system. Subsequently, an additional XT system was deployed for the deterioration of mitral regurgitation caused by COWL, without any complications. Discussion: The MitraClip G4 system offers four size variations, providing a larger grasping area and increased flexibility for accessing complex lesions. Furthermore, the complication rate decreased with increasing operator experience and device generation. However, it has been reported that COWL can occur after the clip is deployed during TEER. Although the mechanism of COWL is unclear, the nature and mobility of the valve leaflets and the product specificity of the MitraClip may be involved.

Degradation of a novel magnesium alloy-based bioresorbable coronary scaffold in a swine coronary artery model.

The objective of the study is to investigate the safety, feasibility, and degradation profile of a novel Mg alloy-based bioresorbable coronary scaffold (JFK-PRODUCT BRS) with thin struts (110 µm). Polymer- or Mg alloy-based BRSs have not replaced nondegradable metal stents because of the higher prevalence of scaffold thrombosis and restenosis in clinical practice; these poor clinical outcomes were due to inadequate scaffold designs, including thick struts (more than 150 µm) and their inappropriate degradation processes. Fourteen healthy pigs received 17 JFK-PRODUCT BRSs in the coronary arteries and were sacrificed at 1, 6, 12, 18, and 26 months after implantation. Angiography, optical coherence tomography, microfocus X-ray computed tomography (µCT), scanning electron microscopy with energy-dispersive X-ray spectrometry (SEM-EDX), and histopathological evaluation were performed. The JFK-PRODUCT had a median percent late recoil of 11.28% at 1 month. The µCT observation confirmed that scaffold discontinuity reached 64.8% at 12 months with increased scaffold inner area thereafter, suggesting artery positive remodeling. The inflammation was mild, peaked at 18 months, and decreased thereafter. The SEM-EDX analysis demonstrated gradual degradation of the scaffold with formation of inorganic deposits, presumed to be calcium phosphates. It also revealed the disappearance of calcium phosphates at 26 months, achieving almost complete replacement of the scaffold by biocomponents. The current study demonstrated the safety and feasibility of JFK-PRODUCT with a lower acute recoil rate despite its thin struts. The scaffolds were almost completely disappeared at 26 months after implantation.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Early structural valve deterioration of balloon expandable transcatheter aortic valve leaflets due to intrinsic and extrinsic nodular calcifications in a haemodialysis patient: a case report.

Background: Several reports have shown that transcatheter aortic valves are comparable in durability to surgical aortic valves. However, early structural valve deterioration (SVD) is rarely reported to occur, especially in haemodialysis patients. Case summary: We present a case of rapidly progressive bioprosthetic aortic valve stenosis in a patient with end-stage renal disease secondary to diabetic nephropathy in an 83-year-old female admitted due to progressive dyspnoea and orthopnoea. A 23 mm sized SAPIEN3 bioprosthetic aortic valve showed normal function for the first year after transcatheter aortic valve implantation (TAVI), but then rapidly developed stenosis and required acute hospitalization for heart failure a year and a half after surgery. Emergent surgical aortic valve replacement with a 19 mm On-X valve (CryoLife, Kennesaw, GA, USA) was performed. Pathological examination of the explanted SAPIEN 3 valve demonstrated severely degenerated bioprosthetic pericardial leaflets with severe intrinsic and extrinsic nodular calcifications, which could limit the leaflet motion. Discussion: There is a lack of reports on the long-term procedural outcomes of TAVI in haemodialysis patients. The development of SVD in patients undergoing dialysis is multifactorial and has yet to be fully elucidated. In the presented case, the removed TAVI valve had severe extrinsic calcified nodules alongside a fibrin thrombus. Considering these pathological findings, antithrombotic therapy to prevent fibrin thrombus from adhering to the TAVI valve may be important to avoid early SVD.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Prospective deep learning-based quantitative assessment of coronary plaque by computed tomography angiography compared with intravascular ultrasound: the REVEALPLAQUE study.

AIMS: Coronary computed tomography angiography provides non-invasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence (AI) analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicentre international study compared an automated deep learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). METHODS AND RESULTS: The study included clinically stable patients with known coronary artery disease from 15 centres in the USA and Japan. An AI-enabled plaque analysis was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low-attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm, and mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. CONCLUSION: AI-enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.

Rationale and Design of Prospective, Multicenter, Double-Arm Clinical Trial to Investigate the Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus (TOP-HFPEF Trial).

BACKGROUND: Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. METHODS AND RESULTS: The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. CONCLUSIONS: The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Rapid progression of a coronary artery aneurysm caused by IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. IgG4-RD has also been reported in coronary arteries as periarteritis. IgG4-related coronary periarteritis may cause coronary artery aneurysms, and IgG4-related coronary artery aneurysms (IGCAs) are life-threatening. We describe a case of a patient with IGCA that highlights the usefulness and limitations of various IGCA evaluation modalities and provides insight into disease pathophysiology. CASE SUMMARY: A 60-year-old man with IgG4-RD diagnosed 2 years before and with IGCA at the proximal right coronary artery (RCA) on coronary angiography (CAG) 9 months prior to admission to the hospital presented with acute coronary syndrome. Emergent CAG revealed the rapid progression of IGCA at the RCA, an obstruction of the diagonal branch, and stenosis of the left anterior descending artery (LAD) and the high lateral branch (HL). The patient underwent percutaneous coronary intervention for the diagonal branch. The RCA aneurysm was resected and bypassed with a saphenous vein graft (SVG); coronary bypass grafting (left internal mammary artery to LAD and SVG to HL) was performed. Pathological findings showed inflammatory cell infiltration and disruption of the elastic plate. CONCLUSION: IGCAs require careful follow-up with computed tomography scans for early detection of aneurysmal enlargement.

Biological differences of three paclitaxel- and sirolimus-coated balloons on coronary lesions in a rabbit model.

BACKGROUND: Drug-coated balloons (DCBs) are important treatment options for coronary artery disease; however, randomised controlled trials comparing various DCB technologies are sparse, and further investigations are needed. AIMS: This preclinical study aimed to histologically and biologically compare the drug effects and safety of a low-dose paclitaxel-coated DCB (PCB; AGENT), a regular-dose PCB (SeQuent Please NEO) and a sirolimus-coated DCB (SCB; MagicTouch). METHODS: The DCBs were inflated in the healthy iliac arteries of 18 rabbits, which were euthanised after 28 days. The treated iliac arteries and distal skeletal muscles were histopathologically evaluated, and drug concentrations were measured. RESULTS: In the histopathological evaluation, the medial smooth muscle cell loss score regarding depth, an indicator of drug efficacy, was significantly higher with AGENT and SeQuent Please NEO than with MagicTouch (4.0 [3.6-4.0] vs 3.7 [3.7-4.0] vs 2.2 [2.0-2.4]), with significant differences in comparisons between AGENT and MagicTouch (p<0.01) and between SeQuent Please NEO and MagicTouch (p<0.01). AGENT and SeQuent Please NEO showed comparable drug concentrations in the treated artery (p=0.61). In contrast, the drug concentrations in distal skeletal muscles were the highest for MagicTouch, followed by SeQuent Please NEO and AGENT (28.07 [13.19-52.46] ng/mg vs 0.66 [0.22-3.76] ng/mg vs 0.25 [0.04-3.23] ng/mg, respectively). CONCLUSIONS: This study demonstrated that PCBs might have higher efficacy and lower drug concentrations in distal skeletal muscles than the MagicTouch SCB. The efficacy of the AGENT low-dose PCB and the SeQuent Please NEO regular-dose PCB was comparable.

Transcatheter aortic valve implantation for structural valve deterioration of homograft surgical aortic valve using SAPIEN3 Ultra RESILIA: a case report.

Background: There are a few case reports regarding transcatheter aortic valve implantation (TAVI) for deteriorated surgical homograft. Case summary: We present a case of severe structural valve deterioration (SVD) of homograft surgical aortic valve presenting severe aortic regurgitation in an 84-year-old man with decompensated heart failure. We performed TAVI in homograft valve using 23 mm SAPIEN3 Ultra RESILIA. The resulting grade of paravalvular regurgitation was trace, the post-operative effective orifice area (EOA) was 1.66 cm2 (index EOA: 1.19 cm2/m2), and device success was achieved. Discussion: Stented bioprosthetic valves are more commonly implanted than mechanical and stentless bioprosthetic valves. In the 1980s and the early 1990s, homografts became particularly popular as alternatives to stented valves. There are several reports of TAVI for homograft SVD, but the paravalvular leakage grade is worse than that of redo-surgical aortic valve replacement, although the mortality rate is lower. However, the valves used in these reports were from older valves such as SAPIEN XT or SAPIEN3. There are no reports using SAPIEN3 Ultra RESILIA with a significant reduction in paravalvular leak due to an external textured polyethylene terephthalate skirt extending 40% higher above the valve inflow than the classical SAPIEN3, which is now available. Transcatheter aortic valve implantation using SAPIEN3 Ultra RESILIA showed good therapeutic efficacy.