A number of recent epidemiological studies have associated the clonal expansion of hematopoietic cells, a process referred to as clonal hematopoiesis, with increased mortality. Clonal hematopoiesis increases the risk of hematological cancer, but this overall risk cannot account for the increase in mortality in the general population. Surprisingly, these mutations have also been associated with higher rates of cardiovascular disease, suggesting a previously unrecognized link between somatic mutations in hematopoietic cells and chronic disease. Here, we review recent epidemiological and experimental studies on clonal hematopoiesis that relate to cardiovascular disease.
The roles that blood vessels play in the maintenance of organs and tissues in addition to the delivery of oxygen and nutrients are being gradually clarified. The maintenance of tissue-specific organ stem cells, such as hematopoietic and neuronal stem cells, is supported by endothelial cells (ECs), which represent an important component of the stem cell niche. The maintenance of organogenesis, for example, osteogenesis and liver generation/regeneration, is supported by molecules referred to as “angiocrine signals” secreted by EC. The mechanisms responsible for the well-known functions of blood vessels, such as thermoregulation and metabolism, especially removal of local metabolites, have now been determined at the molecular level. Following the development of single-cell genetic analysis, blood cell heterogeneity, especially of mural cell populations, has been established and tissue-specific blood vessel formation and function are now also understood at the molecular level. Among the heterogeneous populations of ECs, it seems that a stem cell population with the ability to maintain the production of ECs long-term is present in pre-existing blood vessels. Neovascularization by therapeutic angiogenesis yields benefits in many diseases, not only ischemic disease but also metabolic disease and other vascular diseases. Therefore, vascular endothelial stem cells should be considered to use in vascular regeneration therapy.
Background: The arrhythmogenic role of complex atrial morphology has not yet been clearly elucidated. We hypothesized that bumpy tissue geometry can induce action potential duration (APD) dispersion and wavebreak in atrial fibrillation (AF).
Methods and Results: We simulated a 2D-bumpy atrial model by varying the degree of bumpiness, and 3D-left atrial (LA) models integrated by LA computed tomographic (CT) images taken from 14 patients with persistent AF. We also analyzed wave-dynamic parameters with bipolar electrograms during AF and compared them with LA-CT geometry in 30 patients with persistent AF. In the 2D-bumpy model, APD dispersion increased (P<0.001) and wavebreak occurred spontaneously when the surface bumpiness was greater, showing phase transition-like behavior (P<0.001). The bumpiness gradient 2D-model showed that spiral wave drifted in the direction of higher bumpiness, and phase singularity (PS) points were mostly located in areas with higher bumpiness. In the 3D-LA model, PS density was higher in the LA appendage (LAA) compared with other parts of the LA (P<0.05). In 30 persistent-AF patients, the surface bumpiness of LAA was 5.8-fold that of other LA parts (P<0.001), and exceeded critical bumpiness to induce wavebreak. Wave dynamics complexity parameters were consistently dominant in the LAA (P<0.001).
Conclusions: Bumpy tissue geometry promoted APD dispersion, wavebreak, and spiral wave drift in in-silico human atrial tissue, and corresponded to clinical electroanatomical maps.
Background: It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardiac myocytes.
Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Cell length (contraction) was monitored in electrically stimulated and non-stimulated conditions. Ouabain treatment increased contractility, frequency of spontaneous contractions and apoptosis compared to control cells. Carvedilol (1 µmol/L) or VK-II-86 (1 µmol/L) did not affect ouabain-induced inotropy, but significantly reduced the frequency of Ca2+ waves, spontaneous contractions and cell death evoked by ouabain treatment. This antiarrhythmic effect was not associated with a reduction in Ca2+ calmodulin-dependent protein kinase II (CaMKII) activity, phospholamban and ryanodine receptor phosphorylation or SR Ca2+ load. Similar results could be replicated in human cardiomyocytes derived from stem cells and in a mathematical model of human myocytes.
Conclusions: Carvedilol and VK-II-86 are effective to prevent ouabain-induced apoptosis and spontaneous contractions indicative of arrhythmogenic activity without affecting inotropy and demonstrated to be effective in human models, thus emerging as a therapeutic tool for the prevention of digitalis-induced arrhythmias and cardiac toxicity.
Background: Implantable cardioverter defibrillators (ICDs) are being used with increasing frequency in children. Our aim was to examine the current trend of pediatric ICD implantation in Japan.
Methods and Results: Data was extracted from the Japanese Cardiac Device Treatment Registry (JCDTR), a nation-wide registry started in 2006. All patients aged less than 18 years who had an ICD implantation registered between 2006 and 2016 were included in the analysis. A total of 201 patients were included, with a median age of 16 years (range 1–18). The underlying cardiac diagnosis was primary electrical disease (67%), cardiomyopathy (26%) and congenital heart disease (4%), with idiopathic ventricular fibrillation (29%) and long QT syndrome (21%) being the 2 most common diagnoses. Implantation indication was primary prevention in only 30 patients (15%). There were 27 patients (13%) aged ≤12 years, with a larger proportion of patients with cardiomyopathy (33%). The indication in younger children was secondary prevention in all cases. Younger children may be under-represented in our study given the nature of the database as it is a predominantly adult cardiology database.
Conclusions: In the past decade, ICD implantation has been performed in approximately 20 children per year in Japan, mostly for secondary prevention. There was no increase in the trend nor a change in age distribution.
Background: Identifying who among current Japanese patients with prior myocardial infarction (MI) would benefit from an implantable cardioverter-defibrillator (ICD) is imperative. Accordingly, this study seeks to determine whether single-photon emission computed tomography (SPECT) can help identify such patients.
Methods and Results: This retrospective study enrolled 60 consecutive patients with prior MI who underwent stress thallium-201 SPECT and ICD implantation from February 2000 to October 2014. Occurrence of arrhythmic death and/or or appropriate ICD therapy, defined as shock or antitachycardia pacing for ventricular fibrillation or tachycardia, was identified until November 2016. During the median follow-up interval of 6.6 years, 18 (30%) patients experienced arrhythmic death and/or appropriate ICD therapy. Multivariate Cox proportional hazard regression analysis revealed that the summed stress score (SSS) [hazard ratio (HR)=1.14; P=0.005] and left ventricular ejection fraction (LVEF) at rest (HR=0.92; P=0.038) were significantly associated with the occurrence of arrhythmic events. Patients with SSS ≥21 and LVEF ≤30%, which were determined to be the best cutoff points, had significantly higher incidence of the arrhythmic events than the other patients (64% vs. 11%; HR=7.18; log-rank P=0.001).
Conclusions: SSS using stress thallium-201 SPECT in combination with LVEF can help determine the need for ICD therapy among current Japanese patients with prior MI.
Background: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective non-interventional study of stroke prevention in patients with newly diagnosed non-valvular AF (NAVF) that is being conducted in 35 countries.
Methods and Results: A total of 52,081 patients with a new diagnosis of NVAF were enrolled prospectively in GARFIELD-AF. Of these, 4859 (9.3%) were recruited in Japan (2010–2016). In cohort 1 (2010–2011), few patients were on non-vitamin K antagonist oral anticoagulants (NOAC) globally. From cohort 2 onwards (2011–2016), however, there was a rapid increase in NOAC use around the globe, especially in Japan. By the last year of enrolment (2015–2016), 67.9% of patients in Japan and 43.1% of patients globally were on NOAC±antiplatelet therapy (AP). In Japan and globally, 17.0% and 12.2% of patients, respectively, did not receive stroke prevention treatment. Few patients in Japan (5.7%) received AP only. Compared with the other countries, the unadjusted rates of all-cause mortality and major bleeding were low, while rates of stroke/systemic embolism were similar after 1 year of follow-up.
Conclusions: GARFIELD-AF continues to provide important information on the homogeneity and heterogeneity of baseline characteristics and treatment patterns in patients with newly diagnosed NVAF. This diversity reflects the differences in outcomes in Japan compared with the rest of the world.
Background: The effects of catheter ablation for atrial fibrillation (AF) on hemodynamic parameters in patients with preserved left ventricular (LV) systolic function are unclear.
Methods and Results: We enrolled 178 patients with AF (paroxysmal, 108; persistent, 70) with preserved LV systolic function who underwent AF ablation. The stroke volume index (SVI) was repeatedly measured using impedance cardiography. Reduced SVI (SVI, <33 mL/m2) was observed in 55% of patients before ablation. In patients with paroxysmal AF, the SVI did not change immediately after ablation (from 35±6 mL/m2to 35±5 mL/m2; P=0.652); however, it increased 1 month after ablation and further increased 6 months after ablation (1 month, 37±6 mL/m2, P<0.001; 6 months, 38±6 mL/m2, P<0.001). In patients with persistent AF, the SVI increased immediately after ablation (from 30±5 mL/m2to 36±6 mL/m2; P<0.001) and further increased until 6 months after ablation (1 month, 37±6 mL, P<0.001; 6 months, 38±5 mL/m2, P<0.001). The baseline SVI was the strongest predictor of the cardiac function improvement with an area under the curve of 0.828.
Conclusions: The restoration and maintenance of sinus rhythm using catheter ablation increased the SVI in patients with preserved LV systolic function.
Background: Pulmonary vein isolation (PVI) by means of cryoballoon is increasingly being used for the treatment of atrial fibrillation (AF). This study assessed whether the left atrial volume index (LAVI) predicts AF recurrence following PVI by means of 2nd-generation cryoballoon (Cryoballoon Advance; CB-A) when comparing persistent AF (PeAF) and paroxysmal AF (PAF).
Methods and Results: Patients with drug-resistant AF and undergoing preprocedural computed tomography (CT) and PVI with CB-A were included. LAV was estimated from 3D CT images. A total of 417 patients with AF were included (95 PeAF, 322 PAF patients). After a mean of 22.1±9.4 months follow-up, 45/95 (47%) PeAF patients and 254/322 (79%) PAF patients had no recurrence. LAVI was an independent predictor for AF recurrence in PeAF patients (hazard ratio 1.042 per 1 mL/m2; 95% confidence interval 1.006–1.080, P=0.02), but not in PAF patients. In PeAF patients with LAVI ≤61 mL/m2, the freedom from recurrence was 78.5% vs. 22.2% in those with LAVI >61 mL/m2 (hazard ratio 5.771, 95% confidence interval 2.434–13.682, P<0.001), and the mid-term success rate was comparable with PAF patients.
Conclusions: LAVI predicted AF recurrence after PVI using CB-A in PeAF patients but not in PAF patients. If LAVI was ≤61 mL/m2, the mid-term efficacy among PeAF patients was equivalent to that for PAF patients.
Background: Recurrent ventricular tachycardia (VT) and fibrillation (VF), the so-called “electrical storm” (ES) occurs at various stages of acute myocardial infarction (AMI), but its incidence, background, and short-term prognosis remain unclear.
Methods and Results: A retrospective observational study was performed using the registry database of the Tokyo CCU Network. The individual data of 6,003 patients with AMI during 2011–2012 was corrected. ES was defined as more than 3 episodes of sustained VT/VF during a 24-h period as first documented after hospitalization. ES occurred in 55 patients after admission (0.9%). The ES(+) group had more severe heart failure (Killip class >III), more extensive MI (peak-CK), greater inflammatory reaction (CRP), history of diabetes, and more frequent application of hemodialysis as compared with the ES(−) group (n=5,865). When the ES patients were divided into Early-ES (n=37: ES occurred ≤48 h after the onset of MI) and Late-ES (n=15 >48 h after onset of MI) groups, logistic regression analysis revealed that Early-ES was associated with severity of MI, whereas Late-ES was related to systemic disorders, including inflammation, renal dysfunction, or diabetes. Late-ES was an independent predictor of in-hospital death.
Conclusions: In-hospital ES was a rare clinical manifestation of AMI. The features and background of the ES varied as time elapsed after admission for MI.
Background:Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).
Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA.
Conclusions:No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.
Background: The aim of this single-center study was to report the midterm clinical outcomes and hemodynamic performance of the St Jude Medical Epic porcine bioprosthesis, a tricomposite glutaraldehyde-preserved porcine bioprosthesis, in mitral position.
Methods and Results: Between January 2011 and March 2017, 117 patients (62 men, 55 women; mean age, 66.7±12.8 years) who underwent mitral valve replacement (MVR) with the Epic valve were retrospectively analyzed for early and mid-term morbidity and mortality. The mean follow-up period was 2.6±1.7 years. Three operative deaths occurred, and the operative mortality rate was 2.6%. Sixteen patients died during the follow-up period. On Kaplan-Meier analysis, freedom from all-cause death and major adverse cardiovascular and cerebrovascular events at 5-year follow-up were 80.9% and 54.8%, respectively. There were 6 reoperations: 2 for structural valve deterioration (SVD), 2 for prosthetic valve endocarditis, and 2 for thrombosis. Freedom from valve-related reoperation and SVD at 5 years were 89.0% and 93.1%, respectively. On multivariate analysis, age ≥71 years (HR, 6.78; 95% CI: 2.12–25.2, P<0.01), and NYHA functional class ≥III (HR, 3.20; 95% CI: 1.03–10.4, P=0.04) were independent predictors for all-cause death. Mean mitral pressure gradient at 1 year and 2 years were 5.1±1.9 mmHg and 4.5±1.4 mmHg, respectively.
Conclusions: Mid-term clinical results and durability of the Epic valve in the mitral position are satisfactory.
Background: Orthotopic heart transplantation (HT) is the treatment of choice for patients with end-stage heart failure (HF). The bicaval technique was introduced as a safe alternative minimizing modification of atrial geometry. The modification of bicaval anastomosis is suggested to compensate for caliber mismatch and small donor. The present study was performed to compare these 2 techniques in terms of postoperative CT scan and clinical outcomes.
Methods and Results: Retrospectively, 158 consecutive patients with end-stage HF underwent orthotopic HT between January 2009 and June 2013 were analyzed. Of these, we excluded 3 patients with total HT. The study group was divided into modified technique (n=37) or conventional technique (n=118). A total of 113 patients (modified: n=29, conventional: n=84) were examined with cardiac CT. Discrepancy in the size of the vena cava compared with that of the anastomosis site was assessed. There was no significant difference in the complication and survival rates. There was 1 incident of moderate-to-severe tricuspid valve regurgitation in the modified group (n=1, 2.7%). Both the SVC ratio (1.07±0.13 vs. 1.28±0.32, P=0.001) and IVC ratio (1.06±0.07 vs. 1.13±0.19, P=0.009) were higher in the conventional group, which meant more stenotic imaging findings were observed in the conventional group.
Conclusions: Orthotopic HT with modified bicaval anastomosis is an attractive alternative with easy orientation and equivocal outcomes.
Background: The long-term outcomes of complete revascularization (CR) in patients with left ventricular (LV) dysfunction undergoing coronary artery bypass grafting (CABG) remain unclear.
Methods and Results: We evaluated a consecutive series of 111 patients with LV ejection fraction ≤35% who underwent isolated first-time CABG: 63 underwent CR and 48 underwent incomplete revascularization (IR). At a median follow-up of 10.1 years, the rates of death from any cause, cardiac death, and major adverse cardiac and cerebrovascular events (MACCE) were significantly greater in the IR group. After adjusting for propensity score, no significant difference was found between the CR and IR groups regarding death from any cause (hazard ratio [HR], 1.45; 95% CI: 0.75–2.81; P=0.271) and cardiac death (HR, 1.45; 95% CI: 0.68–3.10; P=0.337). In contrast, IR increased the risk of MACCE (HR, 1.92; 95% CI: 1.08–3.41; P=0.027), which was principally attributed to an increased risk of repeat revascularization (HR, 3.92; 95% CI: 1.34–11.44; P=0.013).
Conclusions: Although IR was not significantly associated with an increased risk of long-term mortality in patients with LV dysfunction who underwent CABG, CR might reduce the risks of repeat revascularization and subsequent MACCE.
Background: To determine the impact of cardiac function and type of mitral valve (MV) surgery on blood flow and energy loss in the left ventricle (LV).
Methods and Results: This study enrolled patients with ejection fraction (EF) <35% or >50%; both groups had native (n=27 and n=16), repaired (n=19 and n=33), or prosthetic MVs (n=18 and n=19). They were examined by echocardiography-based vector flow mapping to assess the LV blood flow pattern and energy loss per heartbeat. Among patients with preserved EF, those with native MVs displayed a clockwise vortex and relatively low energy loss. In contrast, MV replacement induced a counterclockwise vortex producing higher energy loss than MV repair, which induced a normal clockwise vortex. This indicated the need for MV repair to minimize LV energy loss after surgery. Among the patients with reduced EF, those with native MVs showed a blood flow pattern similar to those with preserved EF and native MVs; furthermore, those with repaired MVs and half of the patients with prosthetic MVs displayed a clockwise vortex, resulting in no difference in energy loss between the 2 types of MV surgery.
Conclusions: Cardiac function and the type of MV surgery are factors affecting the postoperative LV blood flow pattern. MV replacement resulted in abnormal blood flow with normal cardiac function, whereas advanced cardiomyopathy modified the blood flow pattern post-MV replacement.
Background: Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether post-OHCA outcome correlated with renal function early after OHCA.
Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45–59 (n=1,311), 30–44 (n=1,441), and <30 mL/min/1.73 m2(n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54–1.03), 0.42 (95% CI: 0.28–0.62), and 0.43 (95% CI: 0.28–0.68) for eGFR 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52–1.06), 0.40 (95% CI: 0.25–0.64), and 0.48 (95% CI: 0.29–0.81), respectively.
Conclusions: An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.
Background: In recent years, individuals with high serum total cholesterol (TC) have been more likely to modify their diet by reducing their intake of dietary lipids. The aim of this study was to investigate time-related changes in the relationships between the Keys score, dietary lipids, and TC between 1980 and 2010 in representative Japanese populations.
Methods and Results: We used 3 cross-sectional cohort studies conducted among Japanese representative populations in 1980, 1990, and 2010 (NIPPON DATA80/90/2010) for the analyses. We analyzed data for 10,365, 7,714, and 2,657 participants, respectively, in each dataset. The relationships between TC and the Keys score (calculated by dietary lipids, cholesterol, and energy intake)/dietary lipids were examined. In men, a 1-unit higher Keys score correlated with 0.92 mg/dL and 0.64 mg/dL TC in 1980 and 1990, respectively, but not in 2010. In women, a 1-unit higher Keys score correlated with 0.70 mg/dL and 0.74 mg/dL TC in 1980 and 1990, respectively, but with 0.33 mg/dL in 2010. In men and women, dietary cholesterol, saturated fatty acid (SFA), and trans fatty acid (TFA) levels were positively associated with TC concentrations in 1980 and 1990, but not in 2010.
Conclusions: In these representative Japanese populations, a higher Keys score as well as dietary cholesterol, SFA, and TFA levels correlated with higher TC concentrations in 1980/1990, but the relationships were weaker or not observed in 2010.
Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated.
Methods and Results: We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0–4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5–6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15–2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, −0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes.
Conclusions: Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.
Background: The respiratory instability frequently observed in advanced heart failure (HF) is likely to mirror the clinical status of worsening HF. The present multicenter study was conducted to examine whether the noble respiratory stability index (RSI), a quantitative measure of respiratory instability, reflects the recovery process from HF decompensation.
Methods and Results: Thirty-six of 44 patients hospitalized for worsening HF completed all-night measurements of RSI both at deterioration and recovery phases. Based on the signs, symptoms, and laboratory data during hospitalization, the Central Adjudication Committee identified 22 convalescent patients and 14 patients with less extent of recovery in a blinded manner without any information on RSI or other respiratory variables. The all-night RSI in the convalescent patients was increased from 27.8±18.4 to 34.6±15.8 (P<0.05). There was no significant improvement of RSI, however, in the remaining patients with little clinical improvement. Of the clinical and laboratory variables, on stepwise linear regression modeling, body weight, peripheral edema, and lung congestion were closely related to the RSI of recovered patients and accounted for 56% of the changes in RSI (coefficient of determination, R2=0.56).
Conclusions: All-night RSI, a quantitative measure of respiratory instability, could faithfully reflect congestive signs and clinical status of HF during the recovery process from acute decompensation.
Background: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences.
Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58–2.14).
Conclusions: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.
Background: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases).
Methods and Results: We prospectively enrolled 22 patients admitted for HF and 11 age-, sex-, and comorbidity-matched hospitalized control subjects without a history of HF. Gut flora and plasma microbiome-related metabolites were evaluated by amplicon sequencing of the bacterial 16S ribosomal RNA gene and capillary electrophoresis time-of-flight mass spectrometry, respectively. HF patients were evaluated in both the Decomp and Comp phases during hospitalization. The phylum Actinobacteria was enriched in HF patients compared with control subjects. At the genus level, Bifiodobacterium was abundant while Megamonas was depleted in HF patients. Meanwhile, plasma concentration of trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, was increased in HF patients (Decomp HF vs. control, P=0.003; Comp HF vs. control, P=0.004). A correlation analysis revealed positive correlations between the abundance of the genus Escherichia/Shigella and levels of TMAO and indoxyl sulfate (IS, a microbe-dependent uremic toxin) in Comp HF (TMAO: r=0.62, P=0.002; IS: r=0.63, P=0.002). Escherichia/Shigella was more abundant in Decomp than in Comp HF (P=0.030).
Conclusions: Our results suggest that gut microbiome composition and microbiome-related metabolites are altered in HF patients.
Background: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens.
Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut.
Conclusions: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.
Background:Data on the clinical outcomes of percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) in patients with acute coronary syndrome (ACS) are limited. Therefore, this study aimed to assess the clinical outcome of patients with ACS who underwent PCI for LMCA culprit lesion.
Methods and Results:Of 1,809 patients enrolled in the Assessing Optimal Percutaneous Coronary Intervention for the LMCA (AOI-LMCA) registry (a retrospective 6-center registry of consecutive patients undergoing LMCA stenting in Japan), the current study population consisited of 1,500 patients with unprotected LMCA stenting for LMCA ACS (ACS with shock: 115 patients, ACS without shock: 281 patients) and stable CAD (1,104 patients). The cumulative 180-day incidence of death was markedly higher in the ACS with shock group than in the other groups (49.5%, 8.6%, and 3.3%, respectively; P<0.0001), but mortality beyond 180-day was not significantly different among the 3 groups (30.2%, 20.4%, and 19.5%, respectively; P=0.65). In the ACS with shock group, the initial TIMI flow grade did not affect 5-year mortality (57.1% and 62.2%, P=0.99), but in the ACS without shock group, 5-year mortality was significantly higher in patients with initial TIMI flow grade ≤1 than in patients with TIMI flow grade ≥2 (44.4% and 23.7%, respectively; P=0.008).
Conclusions:In patients with LMCA ACS, survival correlates with baseline hemodynamic and coronary flow status.
Background:Patent ductus arteriosus (PDA) is common in premature infants. Cyclooxygenase inhibitors such as indomethacin, which inhibit prostaglandin E2(PGE2) synthesis, are currently the sole treatments for patients with PDA. Their efficacy are, however, frequently limited, and adverse effects are problematic. Because the PGE2-specific receptor EP4 selectively expresses in rat ductus arteriosus (DA), it is hypothesized that EP4 inhibition would promote DA closure with fewer side-effects.
Methods and Results:A new chemical compound EP4 antagonist, RQ-15986 (renamed from CJ-042794), was used. Whether RQ-15986 selectively contracted the DA was examined by measuring the isometric tension of rat DA ex vivo at embryonic day 19 (e19) and e21. RQ-15986 at a dose of 10−6mol/L increased the isometric tension of the DA up to 44.8±6.2% and 69.1±12.9% to the maximal KCl-induced tension at e19 and e21 respectively. The effect of RQ-15986 on rat DA in vivo was also tested by using a rapid whole-body freezing method. RQ-15986 inhibited PGE1-induced DA dilatation in neonatal rats. Furthermore, RQ-15986 contracted the DA in a dose-dependent manner, and the constriction was greater at e21 than at e19. Moreover, RQ-15986 did not contract the aorta or the marginal artery of the colon.
Conclusions:EP4 inhibition contracts rat DA with fewer side-effects. EP4 inhibition is a promising alternative strategy to treat patients with PDA.
Background: Therapeutic angiogenesis with basic fibroblast growth factor (bFGF) with atelocollagen was confirmed in a study using a limb ischemia mouse model. Because the number of elderly patients with critical limb ischemia (CLI) is increasing, particularly that caused by arteriosclerosis obliterans (ASO), the development of less invasive angiogenesis therapies desired.
Methods and Results: This first-in-man clinical study was designed to assess the safety and efficacy of i.m. injection of bFGF with atelocollagen. Human recombinant bFGF (200 μg), combined with 4.8 mL 3% atelocollagen solution, was prepared and injected into the gastrocnemius muscle of the ischemic leg. The primary endpoint was safety, evaluated on all adverse events over 48 weeks after this treatment. The secondary endpoint was efficacy, evaluated by improvement of ischemic symptoms. No serious procedure-related adverse events were observed during the follow-up period. Visual analogue scale (VAS) score was significantly improved at 4, 24 and 48 weeks compared with baseline (P<0.05), and 7 patients became pain free during the follow-up period. Fontaine classification was improved in 4 of 10 patients at 48 weeks. Cyanotic lesions disappeared in 2 patients at 4 weeks.
Conclusions: I.m. injection of bFGF with atelocollagen is safe and feasible in patients with CLI. Randomized controlled trials are therefore needed to confirm these results.
Background: Despite the cosmetic benefits of the minimally invasive approach for mitral disease, the clinical benefit and risk are not fully known. We investigated the benefit and risk of minimally invasive mitral valve (MV) repair for type II dysfunction using propensity score-matched analysis.
Methods and Results: Since 2001, 602 patients have undergone MV repair for type II dysfunction (464 with conventional median sternotomy and 138 with the minimally invasive approach). One-to-one matched analysis using the estimated propensity score based on 23 factors resulted in 93 well-matched patient pairs. There was no in-hospital death in both groups. The operation time was significantly shorter (P=0.002), blood transfusion was less frequent (P=0.04), extubation at the day of surgery was more frequently performed (P=0.017), and the length of hospital stay was significantly shorter in the minimally invasive group than in the sternotomy group (P<0.0001). On postoperative (P=0.02) and 1-year echocardiography (P=0.04), ejection fraction was lower in the minimally invasive group than in the sternotomy group. There were no significant differences in postoperative cerebral infarction, aortic dissection, deep sternal infection, or mid-term outcome between the groups.
Conclusions: Standard sternotomy and the minimally invasive approach provide similar good quality of MV repair for type II dysfunction. The minimally invasive approach is more likely to contribute to fast-track perioperative treatment than the standard sternotomy approach.
Background: To obtain a saphenous vein graft (SVG) for coronary artery bypass grafting (CABG), the benefit of using a no-touch (NT) technique in vascular function has not been fully investigated.
Methods and Results: The pathological and physiological functions of human SVGs with a NT technique to preserve the perivascular adipose tissue (PVAT) and ones obtained by using a conventional (CON) technique removing PVAT, were examined. Immunohistochemistry of the section of SVGs showed that the phosphorylation of endothelial nitric oxide synthase in the endothelium of the NT group was more responsive to vascular endothelial growth factor. A myograph of SVGs showed greater contraction with phenylephrine in the NT group. However, the strong contraction was eliminated in SVGs taken by electrocautery. In the 10 patients whose SVGs were taken without electrocautery, endothelial-dependent relaxation with bradykinin was apparently increased in the CON group more than in the NT group. Smooth muscle relaxation with nitroprusside was higher in the CON group at the lower concentrations; however, the relaxation became greater in the NT group at the high concentrations. Therefore, the effect of neutralizing PVAT-released factors in the both groups was further examined. After medium of NT and CON were exchanged in half, relaxation of SVGs was immediately restored in the NT group.
Conclusions: The results suggest that the NT technique preserves the functions of vasoconstriction and relaxation. Also, the presence of PVAT-released vasoconstrictive factors was suspected.