Association of Door-to-Balloon Time and one-Year Outcomes in hospital survivors of ST-elevation myocardial infarction.

In this study of 19,824 ST-elevated myocardial infarction (STEMI) patients from the JPCI OUTCOME registry (January 1, 2017, to December 31, 2018), we investigated the association between door-to-balloon time (DTB) and 1-year post-discharge cardiovascular outcomes. Patients with DTB >90 min were older and had higher comorbidities. The incidence of 1-year major adverse cardiovascular events (MACE) showed an incremental increase: 3.7 %, 4.8 %, and 7.7 % for DTB ≤60, DTB 60-90, and DTB >90 groups, respectively. Adjusted hazard ratios (aHR) compared to the DTB 60-90 group were 0.83 (DTB ≤60, p = 0.03) and 1.25 (DTB >90, p = 0.005). Subgroup analysis revealed higher risk for MACE in DTB >90 group for patients aged <70, men, no history of coronary revascularization, and those with cardiac arrest or cardiogenic shock. Conversely, DTB ≤60 group without previous revascularization history had a lower MACE risk (aHR 0.80, p = 0.02). This study, the largest of its kind, demonstrates that a DTB below 90 min is associated with lower 1-year MACE risk, supporting current guidelines, and indicating additional benefits for specific patient subgroups, especially those experiencing their first acute coronary event. The findings underscore the importance of early intervention in primary prevention and emphasize the need for prompt detection of vulnerable plaque.

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150 µg/kg/min) via a peripheral forearm vein for 5 min (FFRA); and we analyzed the FFR value variation in the final 20 s of the 5 min, defining 'Fluctuation' as variation range > 0.03. Then, 2 mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Serum Apolipoprotein-A2 Levels Are a Strong Predictor of Future Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (rs=-0.479). CONCLUSIONS: Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.

Coronary Aneurysm after Excimer Laser Catheter Ablation and Plain Balloon Angioplasty for Chronic Total Occlusion in a Patient with Kawasaki Disease.

A 37-year-old man with a history of Kawasaki disease presented with total occlusion of the right coronary artery. The patient underwent percutaneous coronary intervention (PCI) with excimer laser coronary angioplasty (ELCA) and plain balloon angioplasty (POBA). Three months after PCI, a coronary aneurysm with restenosis was detected at the PCI site, and PCI was performed again using a small balloon. The aneurysm healed three months after the second PCI procedure. This is the first report describing the long-term outcome after an aneurysm caused by PCI with ELCA and POBA.

Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry.

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36-3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13-2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06-1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36-2.98),1.37 (95% CI: 0.75-2.48), and 1.13 (95% CI: 0.75-2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men.

Acute coronary syndrome with simultaneous two-vessel occlusion De Winter ST-segment depression or reciprocal change?

We discuss a case of acute coronary syndrome (ACS) with simultaneous two-vessel occlusions in a man in his 20s. The serial electrocardiograms (ECG) showed very early dynamic changes of ST-T configuration resulting from ischemic zone depth or area between anterior wall versus inferior wall. The upsloping ST depression along with tall tentorial T waves in the precordial leads, as shown in the index ECG, raises the possibilities of a de Winter pattern. The retrospective assessment of the index ECG identified prominent T waves and a mild degree of ST-segment elevations in the inferior leads, given the electrocardiographic findings previously recorded at his workplace medical examination obtained at a later date. If the subtle ST-segment elevations in leads II, III, and aVF and the tall T waves were not overlooked in the index ECG, the probability of reciprocal ST-segment depressions in the precordial leads should also be taken into account. We recognize our ECG findings as intriguing ST-T deviation patterns that can change depending on the time sequence and anatomical dominancy of two infarct-related arteries. We finally suggest physicians should bear in mind the possibility of simultaneous multiple vessel occlusions when they encounter ACS patients with hemodynamic instability as in this present case.

Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Treatment for Repeated In-stent Restenosis in a Coronary Artery.

A 57-year-old woman experienced chest pain. A coronary angiogram revealed middle left anterior descending artery stenosis. Despite receiving adequate anti-hyperlipidemia treatment and undergoing percutaneous coronary intervention (PCI), she experienced angina and required PCI six more times for in-stent restenosis. As she had high lipoprotein (a) [LP-(a)] levels at the seventh PCI procedure, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) was administered, and a reduction in the LP-(a) and low-density lipoprotein cholesterol (LDL-C) values was observed. She experienced no recurrence of angina for five years with PCSK9i treatment. PCSK9i can reduce not only LDL-C but also LP-(a) levels, resulting in cardiac event risk reduction.

Optimal Timing of Serial 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography after Prednisolone Treatment Introduction for Cardiac Sarcoidosis.

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

Baseline Blood Pressure and Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy with Spontaneous Mechanical Alternans.

Objective Spontaneous mechanical alternans (MA), or pulsus alternans, has been observed in heart failure patients with hypertension or tachycardia for 150 years and is considered a sign of a poor prognosis. However, in some dilated cardiomyopathy (DCM) patients with MA, optimal medical therapy (OMT) brings left ventricular reverse remodeling (LVRR), a preferable prognostic indicator. This study examined the probability of LVRR in DCM patients with spontaneous MA and whether or not LVRR can be predicted by the baseline blood pressure or heart rate. Methods We conducted a single-center, retrospective observational study of newly diagnosed DCM patients from January 2017 to December 2020. Results Thirty-three newly diagnosed DCM patients were retrospectively examined. Spontaneous MA was observed during diagnostic cardiac catheterization in at least 1 of the pressure waveforms of the aorta, left ventricle, pulmonary artery, or right ventricle in 10 patients (30%) (MA-group). LVRR after OMT was achieved roughly equally in the MA group (6 of 10, 60%) and the non-MA group (12 of 23, 52%). In the MA group, those who achieved LVRR had a significantly higher baseline systolic aortic pressure (more than 120 mmHg in all 6 patients) than those who did not, although the baseline heart rate did not show a significant correlation with LVRR. In contrast, in the non-MA group, LVRR was unrelated to the baseline aortic pressure or heart rate. Conclusion The probability of LVRR in newly-diagnosed DCM patients with spontaneous MA was similar to that in those without spontaneous MA. Spontaneous MA may not necessarily be a sign of a poor prognosis if observed in patients with a preserved blood pressure.

Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.

Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.

Correlation Between the Japanese Version of the High Bleeding Risk (J-HBR) Criteria and the PRECISE-DAPT Score, and Optimal J-HBR Cut-Off Score to Predict Major Bleeding.

Background: The correlation between the Japanese version of high bleeding risk (J-HBR) criteria and the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score is unknown, as is the relationship of both risk scores with ischemic events. Methods and Results: This study enrolled 842 patients who underwent percutaneous coronary intervention (PCI) between January 2016 and December 2020. The 2 bleeding risk scores at the time of PCI and the subsequent risk of bleeding and ischemic events over a 1-year follow-up were examined. The J-HBR score was significantly correlated with the PRECISE-DAPT score (r=0.731, P<0.001). However, 1 year after PCI, the J-HBR was not significantly associated with the incidence of major bleeding and ischemic events (log-rank, P=0.058 and P=0.351, respectively), whereas the PRECISE-DAPT score predicted both the incidence of major bleeding and ischemic events (log-rank, P=0.006 and P=0.019, respectively). According to receiver operating characteristic curve analysis, a J-HBR score ≥1.5 was significantly associated with a higher cumulative incidence of major bleeding, but not ischemic events (log-rank, P=0.004 and P=0.513, respectively). Conclusions: The J-HBR score is highly correlated with the PRECISE-DAPT score. A J-HBR score ≥1.5 can identify high bleeding risk patients without an increased risk of ischemic events.

Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity.

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then-together with molecules derived from the circulation-promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT. Genetic or pharmacological suppression of coagulation factor-PAR1 signaling in BAT ameliorated its whitening and improved thermogenic response and systemic glucose intolerance in mice with dietary obesity. Conversely, the activation of coagulation factor-PAR1 signaling in BAT caused mitochondrial dysfunction in brown adipocytes and systemic glucose intolerance in mice fed normal chow. These results indicate that BAT produces endogenous coagulation factors that mediate pleiotropic effects via PAR1 signaling under metabolic stress.

Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells.

Accumulation of senescent cells in various tissues has been reported to have a pathological role in age-associated diseases. Elimination of senescent cells (senolysis) was recently reported to reversibly improve pathological aging phenotypes without increasing rates of cancer. We previously identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as a seno-antigen specifically expressed by senescent human vascular endothelial cells and demonstrated that vaccination against Gpnmb eliminated Gpnmb-positive senescent cells, leading to an improvement of age-associated pathologies in mice. The aim of this study was to elucidate whether GPNMB plays a role in senescent cells. We examined the potential role of GPNMB in senescent cells by testing the effects of GPNMB depletion and overexpression in vitro and in vivo. Depletion of GPNMB from human vascular endothelial cells shortened their replicative lifespan and increased the expression of negative cell cycle regulators. Conversely, GPNMB overexpression protected these cells against stress-induced premature senescence. Depletion of Gpnmb led to impairment of vascular function and enhanced atherogenesis in mice, whereas overexpression attenuated dietary vascular dysfunction and atherogenesis. GPNMB was upregulated by lysosomal stress associated with cellular senescence and was a crucial protective factor in maintaining lysosomal integrity. GPNMB is a seno-antigen that acts as a survival factor in senescent cells, suggesting that targeting seno-antigens such as GPNMB may be a novel strategy for senolytic treatments.

Long-Term Outcomes in Patients with Not-Retrieval Inferior Vena Cava Filter Under Anticoagulation.

Since permanent inferior vena cava (IVC) filters increase deep vein thrombosis (DVT), filter retrieval should be performed as possible. Despite the guideline recommendation, IVC filters are not always retrieved in clinical practice. To date, many patients with not-retrieval IVC filters have been prescribed anticoagulant therapy, but the long-term prognosis, including venous thromboembolism (VTE) and bleeding events, remains unknown. In this study, 195 patients who underwent IVC filter implantation between 2006 and 2017 at 3 institutions in Niigata City have been investigated about their deaths, VTE recurrence, and bleeding events. After peaking 2009, the number of IVC filter implantation gradually decreased. During observational period, there were 158 patients with not-retrieval IVC filters (the overall retrieval rate of 19.0%). The not-retrieval group included significantly older and more patients with cancer compared to the retrieval group. Anticoagulation therapy was continued in 88% of the not-retrieval group. During a mean follow-up of 5.0 years, 6 symptomatic DVT events associated with inadequate control of anticoagulation and 13 bleeding events were observed. A total of 52 patients died and only the presence of cancer was prognostic risk factor. Although long-term anticoagulation therapy may be associated with bleeding events, there were few recurrent VTE under optimal anticoagulation. It is anticipated that even if the IVC filter cannot be retrieved, appropriate anticoagulation is useful for prevention of DVT recurrence despite the risk of bleeding.

Improvement of Mass Lesions around Coronary Arteries and Fractional Flow Reserve after Steroid Therapy in Immunoglobulin-G4-related Coronary Periarteritis.

Immunoglobulin-G4-related disease (IgG4-RD) is a multi-organ systemic inflammatory disorder. The ideal treatment of coronary artery involvement in IgG4-RD remains uncertain due to its rarity. We herein report a case of coronary artery involvement with IgG4-RD, wherein mass lesions surrounded the coronary arteries with a moderate stenosis lesion in the right coronary artery (RCA). The fractional flow reserve (FFR) of the RCA was 0.76. After steroid therapy, the mass lesions around the coronary arteries improved. The FFR of the RCA also improved from 0.76 to 0.86. These findings suggest the efficacy of using steroid therapy for coronary artery involvement with IgG4-RD.

Platypnea-orthodeoxia Syndrome Due to Right Ventricular Inflow Tract Obstruction Caused by an Elongated Ascending Aorta: Usefulness of Three-dimensional Cardiac Computed Tomography Imaging in the Sitting Position.

An 84-year-old woman presented with dyspnea in the sitting position. Platypnea-orthodeoxia syndrome (POS) was suspected based on arterial desaturation when her posture changed from the supine to the sitting position. Transesophageal echocardiography showed right-to-left shunting enhancement through a patent foramen ovale (PFO) in the sitting position. Three-dimensional (3D) cardiac CT in the sitting position revealed that the elongated ascending aorta compressed the right ventricular inflow tract, resulting in restricted blood flow to the right ventricle and increased right-to-left shunting. This case highlights the role of 3D-CT in the sitting position in the management of POS.