Echocardiography is an invaluable tool for characterizing cardiac structure and function in vivo. Technological advances in high-frequency ultrasound over the past 3 decades have increased spatial and temporal resolution, and facilitated many important clinical and basic science discoveries. Successful reverse translation of established echocardiographic techniques, including M-mode, B-mode, color Doppler, pulsed-wave Doppler, tissue Doppler and, most recently, myocardial deformation imaging, from clinical cardiology into the basic science laboratory has enabled researchers to achieve a deeper understanding of myocardial phenotypes in health and disease. With high-frequency echocardiography, detailed evaluation of ventricular systolic function in a range of small animal models is now possible. Furthermore, improvements in frame rate and the advent of diastolic strain rate imaging, when coupled with the use of select pulsed-wave Doppler parameters, such as isovolumic relaxation time and E wave deceleration, have enabled nuanced interpretation of ventricular diastolic function. Comparing pulsed-wave Doppler indices of atrioventricular inflow during early and late diastole with parameters that describe the simultaneous myocardial deformation (e.g., tissue Doppler é and á, global longitudinal strain rate and global longitudinal velocity) may yield additional insights related to myocardial compliance. This review will provide a historical perspective of the development of high-frequency echocardiography and consider how ongoing innovation will help future-proof this important imaging modality for 21st century translational research.
Inflammation and fibrosis play an important role in the development and progression of cardiovascular diseases. Acute coronary syndrome (ACS) is caused by rupture of inflamed atherosclerotic plaque and subsequent atherothrombosis. Recent studies have shown that inflammatory markers such as C-reactive protein (CRP) can predict ACS development and have demonstrated the effectiveness of new therapeutic approaches targeting inflammation. Studies have also shown that an enhanced inflammatory response after myocardial infarction (MI) is associated with cardiac rupture, ventricular aneurysm formation, and exacerbation of left ventricular (LV) remodeling. Inflammation is a physiological reaction in which fibrosis is induced to facilitate the healing of tissue damage. However, when an excessive inflammatory response consisting mainly of monocytes/macrophages is induced by various factors, impaired reparative fibrosis and resulting pathological remodeling processes may occur. A similar phenomenon is observed in abdominal aortic aneurysm (AAA) expansion. In contrast, myocardial diseases such as inflammatory dilated cardiomyopathy (DCMI) and valvular diseases such as aortic valve stenosis (AS) are characterized by chronic inflammation mediated mainly by T lymphocytes and the associated enhancement of reactive fibrosis. Thus, inflammation can take 2 paths (the inhibition or promotion of fibrosis), depending on the phase of inflammation, inducing pathological cardiovascular remodeling. Elucidation of the regulatory mechanisms of inflammation and fibrosis will contribute to the development of new therapeutic approaches for cardiovascular diseases.
Delays in the introduction to the Japanese market of drug-eluting stents (DES) developed overseas (i.e., “device lag”) decreased sharply between 2004 and 2012. The reduction accompanied a shift in clinical development from a succession pattern (initial product development and approval overseas followed by eventual entrance into the Japanese market) to parallel development (employing multiregional clinical trials (MRCTs)). Although resource-intensive in the short-term, MRCTs are proving to be an effective tool in simultaneous global product development. Creative study designs and the absence of significant ethnic differences in Japanese subjects regarding DES safety and efficacy and the pharmacokinetic behavior of their coating drugs propel this process. More general factors such as medical need and industry incentivization also encourage this shift. Physicians’ preference for DES over other percutaneous coronary interventions, the expanding global DES market, and streamlined development and approval prospects each motivate industry to continue investing in DES product development. The efforts of various stakeholders were also integral to overcoming practical obstacles, and contributions by ‘Harmonization by Doing’ and a premarket collaboration initiative between the USA and Japan were particularly effective. Today, USA/Japan regulatory cooperation is routine, and Japan is now integrated into global medical device development. MRCTs including Japanese subjects, sites, and investigators are now commonplace.
Background:Rate control is now a front-line therapy in the management of atrial fibrillation (AF). However, the survival benefits of different rate-control medications remain controversial, so we assessed the efficacy of rate-control medications in AF patients with concomitant heart failure (HF).
Methods and Results:From January 2002 to December 2008, a total of 7,034 AF patients with a single type of rate-control drug or without rate-control treatment were enrolled from the Korea National Health Insurance Service database. The death rates over a mean follow-up of 4.5±1.2 years were 12.6% (580 of 4,593) and 29.0% (709 of 2,441) in non-HF and HF patients, respectively. Among the total subjects, the risk of death was lower in patients receiving β-blockers (adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.64–0.88) and calcium-channel blockers (adjusted HR 0.74, 95% CI 0.55–0.98) compared with those who did not receive rate-control medications. In patients without HF, use of rate-control medications did not affect the risk of death. In patients with HF, β-blockers significantly decreased the mortality risk (adjusted HR 0.63, 95% CI 0.50–0.79), whereas use of calcium-channel blockers or digoxin was not associated with death. The results were observed consistently among the cohorts after propensity matching.
Conclusions:Use of β-blockers was associated with a reduced mortality rate for AF patient with HF but not for those without HF. These findings should be examined in a large randomized trial.
Background:Pulmonary vein isolation (PVI) using a cryoballoon (CB) is utilized for treating atrial fibrillation. This study aimed to assess the effect of the procedural characteristics of CB-based PVI (CB-PVI) on late PV reconnections.
Methods and Results:A total of 389 consecutive patients underwent the CB-PVI as their index procedure; 45 consecutive patients underwent re-do procedures (184±87 days after the index CB-PVI). A total of 146 of 178 PVs (82%) remained isolated. The occlusion grade was evaluated in 171 PVs. Complete PV occlusion by the CB (grade 4) was obtained in 122 of 171 PVs (71%) during the index CB-PVI and the PVI status was maintained in 111 PVs (91%). Among the remaining 49 CB-PVIs without complete PV occlusion (grades 1–3), 20 PVs (41%) had late PV reconnections despite successful PVI during the index CB-PVI. A “pull-down maneuver” was performed in 20 PVs because of leakage of blood at the inferior aspect of the PVs, and all those PVs with a successful pull-down maneuver maintained their PVI status. A multivariate analysis demonstrated that the presence of complete PV occlusion was the only independent predictor for persistence of PVI.
Conclusions:The occlusion grade was a reliable predictor of the long-term durability of PVI.
Background:Real-time recording of pulmonary vein isolation (PVI) using a circular mapping catheter has become a key aspect of cryoballoon (CB) ablation. The aim of this study was to investigate the procedural safety, efficacy and rate of real-time pulmonary vein (PV) recording using a novel circular mapping catheter with a 25-mm loop size for CB-based PVI.
Methods and Results:A total of 40 patients with symptomatic atrial fibrillation (AF) underwent PVI using a second-generation CB and a novel 25-mm circular mapping catheter. A total of 159 PV were identified and successfully isolated. Real-time PV recording was achieved in 80% of the PV. In 3 right inferior PV the circular mapping catheter had to be exchanged for a stiff guidewire due to insufficient mechanical support. Therefore, acute PVI using exclusively the circular mapping catheter was achieved in 156/159 PV (98%). Mean procedure and fluoroscopy times were 66±21 min and 15±6 min, respectively. Transient phrenic nerve palsy occurred in 1 patient as the only procedural complication.
Conclusions:The exclusive use of a novel 25-mm circular mapping catheter for CB ablation of AF results in a real-time PV recording rate of 80% and isolation of 98% of targeted PV.
Background:Atrial fibrillation (AF) is the most common arrhythmia in the ageing population in East Asia. Silent cerebral infarction (SCI) is defined as cerebral infarction in the absence of corresponding clinical symptoms, and is a highly prevalent and morbid condition in AF. SCI is increasingly being recognized as a risk factor for future stroke, which can lead to cognitive decline or dementia. The latter is an increasingly common health problem in East Asia.
Methods and Results:We conducted a meta-analysis to compare the association of AF and SCI between East Asian and non-Asian patients. AF was associated with SCI in patients with no symptomatic stroke history (relative risk [RR], 2.24; 95% CI: 1.26–3.99, I2=83%; P=0.006) although the prevalence varied widely between studies (P for heterogeneity<0.001). In non-Asian patients, the prevalence of SCI in AF is higher than that in controls (RR, 1.85; 95% CI: 1.65–2.08, I2=17%; P<0.001). There was no significant racial difference between Asian and non-Asian studies (P=0.53).
Conclusions:In East Asia, AF was significantly associated with SCI and no racial difference was seen between East Asian and non-Asian patients. The present findings offer clinicians new insights into the association between AF and SCI.
Background:Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple factors, including reduced coagulation factors and a low platelet count.
Methods and Results:In this study, we undertook a post hoc analysis to identify factors associated with increased postoperative blood loss in 97 patients undergoing cardiac surgery with CPB, with fresh frozen plasma administered according to a ROTEM-guided algorithm. We identified 24 patients for the top quartile of postoperative blood loss, >528 mL and defined as having excessive blood loss. Using Spearman’s rank correlation test and multivariable linear regression, we reanalyzed the participants’ demographic, surgical and anesthetic variables, laboratory test results, blood loss, and transfusion data. Univariate analysis indicated that patients who experienced higher postoperative blood loss received a significantly higher heparin dose, had a higher requirement for fresh frozen plasma transfusion during surgery, and had a significantly lower hematocrit and platelet count at the end of surgery compared with patients without excessive blood loss. Multivariate analysis showed that platelet count at the end of surgery (odds ratio 0.780, 95% confidence interval 0.629–0.967; P=0.024) was an independent factor for excessive blood loss.
Conclusions:Low platelet count at the end of surgery was associated with excessive postoperative bleeding during cardiac surgery with CPB.
Background:Histomorphometric evidence of the effect of pulmonary artery banding (PAB) in infancy on pulmonary vascular reverse remodeling has not been fully described.
Methods and Results:We retrospectively reviewed 34 patients who underwent serial lung biopsies before and after PAB.Index of pulmonary vascular disease (IPVD) as a measure of the degree of progression of pulmonary arteriopathy significantly decreased after PAB (1.22±0.25 at 1st and 1.13±0.21 at 2nd biopsy, P=0.04). Additionally,DR=100 µmas an indicator of medial thickness of pulmonary arteries significantly decreased after PAB (15.6±3.7 at 1st and 11.4±2.6 at 2nd biopsy, P<0.0001). Patients were divided into 3 groups by age at PAB: <3 months (Group 1), between 3 and 6 months (Group 2), and >6 months (Group 3). The average secondDR=100 µmof groups 1 and 2 was significantly lower than that of group 3 (11.1±2.2 and 9.8±2.0 vs. 14.9±2.8, respectively; P<0.0001). Additionally, the second IPVD was also significantly lower in groups 1 and 2 than in group 3 (1.1±0.2 and 1.1±0.2 vs. 1.3±0.4, respectively; P=0.02).
Conclusions:Histomorphometric evidence of post-PAB pulmonary vascular reverse remodeling is robust. The magnitude of vascular reversibility is pronounced when PAB is performed before 6 months of age.
Background:Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.
Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (β=0.13, P=0.047) and BNP (β=−0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2at baseline was not associated with differential response to carvedilol therapy. During 3.8±1.4 years follow-up, group [A] had a higher incidence of the composite endpoint of death, hospitalization for cardiovascular causes including HF compared with [N] (P=0.006). Baseline Hb was an independent predictor of the composite endpoint (hazard ratio 0.86, P=0.04), whereas baseline eGFR was not.
Conclusions:Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.
Background:Cardiac recovery and prevention of end-organ damage are the cornerstones of establishing successful bridge to recovery (BTR) in patients with fulminant myocarditis (FM) supported with percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, the timing and method of successful BTR prediction still remain unclear. We aimed to develop a prediction model for successful BTR in patients with FM supported with percutaneous VA-ECMO.
Methods and Results:This was a retrospective multicenter chart review enrolling 99 patients (52±16 years; female, 42%) with FM treated with percutaneous VA-ECMO. The S-group comprised patients who experienced percutaneous VA-ECMO decannulation and subsequent discharge (n=46), and the F-group comprised patients who either died in hospital or required conversion to other forms of mechanical circulatory support (n=53). At VA-ECMO initiation (0-h), the S-group had significantly higher left ventricular ejection fraction (LVEF) and lower aspartate aminotransferase (AST) concentration than the F-group. At 48 h, the LVEF, increase in the LVEF, and reduction of AST from 0-h were identified as independent predictors in the S-group. Finally, we developed an S-group prediction model comprising these 3 variables (area under the curve, 0.844; 95% confidence interval, 0.745–0.944).
Conclusions:We developed a model for use 48 h after VA-ECMO initiation to predict successful BTR in patients with FM.
Background:There is sparse research on whether if early menarche is related to left ventricular (LV) diastolic dysfunction. The present study examined this relationship in Korean women.
Methods and Results:In a cross-sectional study we analyzed the records of 18,910 Korean women (≥30 years) who underwent echocardiography as part of a comprehensive health examination. Age at menarche was assessed using standardized, self-administered questionnaires. Presence of LV diastolic dysfunction was determined from the echocardiographic findings. Of the 18,910 women, 3,449 had LV diastolic dysfunction. Age at menarche was inversely associated with prevalence of LV diastolic dysfunction. In a multivariable-adjusted model, odds ratios (95% confidence interval) for LV diastolic dysfunction comparing menarche age to menarche at 15–18 years were 1.77 (1.38–2.27) for <12 years, 1.31 (1.11–1.54) for 12 years, 1.26 (1.11–1.43) for 13 years, and 1.03 (0.91–1.15) for 14 years (P for trend <0.001). Adjusting for body mass index or percent fat mass partially reduced these associations.
Conclusions:This large study found an inverse relationship between menarche age and LV diastolic dysfunction. Future prospective studies are needed to investigate potential causal relationships.
Background:Anthracycline cardiotoxicity affects clinical outcomes, and its early detection using methods that rely on conventional echocardiography, such as left ventricular ejection fraction (LVEF) is difficult. This study aimed to evaluate the characteristics and the differences in cardiac dysfunction among childhood cancer survivors in 3 age groups using layer-specific strain analysis in a wide age range.
Methods and Results:The 56 patients (median age: 15 [range: 6.8–40.2] years) who had been treated with anthracycline for childhood cancer were divided into 3 age groups (C1: 6–12 years, C2: 13–19 years, C3: 20–40 years) after anthracycline treatment, and 72 controls of similar ages were divided into 3 corresponding groups (N1, N2, and N3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Myocardial damage had not occurred yet in C1. Endocardial CS at the basal level was less in C2 than in N2. Endocardial CS at all levels and midmyocardial CS at the basal and papillary levels were lower in C3 than in N3. LVEF and LS were not significantly different between patients and controls.
Conclusions:Among survivors of childhood cancer, impaired myocardial deformation starts in adolescence and extends from the endocardium towards the epicardium and from the base towards the apex with age. These findings are a novel insight into the time course of anthracycline cardiotoxicity.
Background:Prediction models such as the Seattle Heart Failure Model (SHFM) can help guide management of heart failure (HF) patients, but the SHFM has not been validated in the office environment. This retrospective cohort study assessed the predictive performance of the SHFM among patients with new or pre-existing HF in the context of an office visit.
Methods and Results:SHFM elements were ascertained through electronic medical records at an office visit. The primary outcome was all-cause mortality. A “warranty period” for the baseline SHFM risk estimate was sought by examining predictive performance over time through a series of landmark analyses. Discrimination and calibration were estimated according to the proposed warranty period. Low- and high-risk thresholds were proposed based on the distribution of SHFM estimates. Among 26,851 HF patients, 14,380 (54%) died over a mean 4.7-year follow-up period. The SHFM lost predictive performance over time, with C=0.69 and C<0.65 within 3 and beyond 12 months from baseline respectively. The diminishing predictive value was attributed to modifiable SHFM elements. Discrimination (C=0.66) and calibration for 12-month mortality were acceptable. A low-risk threshold of ∼5% mortality risk within 12 months reflects the 10% of HF patients in the office setting with the lowest risk.
Conclusions:The SHFM has utility in the office environment.
Background:Early-diastolic mitral annular velocity (e′) and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e′ (E/e′) have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.
Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e′ only weakly correlated with τ (r=−0.35, P<0.01), E/e′ modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (β=−0.33, P<0.01) and LV ejection fraction (LVEF) (β=0.44, P<0.001) were the independent determinants of e′, and LV mass index (LVMI) (β=0.37, P<0.001) and LVMDP (β=0.47, P<0.001) were those of E/e′. Additionally, E/e′ significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI.
Conclusions:The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e′, whereas LVMI altered the relationship between LV filling pressure and E/e′. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e′.
Background:Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.
Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665–13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112–2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9.
Conclusions:The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.
Background:There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).
Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684–0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522–1.026).
Conclusions:In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.
Background:The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial.
Methods and Results:We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naïve patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The primary endpoint was the percentage change in non-culprit coronary plaque volume (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n=53; between-group difference, 16.9%, P<0.0001). The percent change in PV was −5.1% in the combination therapy group and −6.2% in the statin alone group (P=0.66), although both groups had reduction of PV compared with baseline (both P<0.01). The percent change in lipid PV did not differ between the groups (4.3 vs. −3.0%, P=0.37).
Conclusions:In statin-naïve patients with ACS, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone. [Clinical Trial Registration: www.clinicaltrials.gov (NCT00549926)]
Background:Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).
Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward.
Conclusions:After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.
Background:High-sensitivity cardiac troponin T (hs-cTnT) is useful for detecting myocardial injury and is expected to become a prognostic marker in patients undergoing non-cardiac surgery. The aim of this pilot study evaluating the efficacy of β-blocker therapy in a perioperative setting (MAMACARI study) was to assess perioperative myocardial injury (PMI) in elderly patients with preserved ejection fraction (EF) undergoing non-cardiac surgery.
Methods and Results:In this prospective observational cohort study of 151 consecutive patients with preserved EF and aged >60 years who underwent non-cardiac surgery, serum levels of hs-cTnT were measured before and on postoperative days 1 and 3 after surgery. PMI was defined as postoperative hs-cTnT >0.014 ng/mL and relative hs-cTnT change ≥20%. A total of 36 (23.8%) of the patients were diagnosed as having PMI. The incidence of a composite of cardiovascular events within 30 days after surgery, including myocardial infarction, stroke, worsening heart failure, atrial fibrillation and pulmonary embolism, was significantly higher in patients with PMI than in patients without PMI (odds ratio (OR) 9.25, P<0.001, 95% confidence interval (CI) 2.65–32.3). Multivariate analysis revealed that left ventricular diastolic dysfunction defined by echocardiography was independently associated with PMI (OR: 3.029, 95% CI: 1.341–6.84, P=0.008).
Conclusions:PMI is frequently observed in elderly patients undergoing non-cardiac surgery. Diastolic dysfunction is an independent predictor of PMI.
Background:Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in autopsy series, but little is known about SRCT, and it is potentially under-diagnosed in clinical practice.
Methods and Results:SRCT identified on OCT were included in a French multicenter series, the Lotus Root French Registry. A total of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years; IQR, 52–65 years); 23/33 patients (70%) presented with angina pectoris and/or dyspnea. Three angiographic aspects were distinguished retrospectively: braided, pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on OCT varied between 20% and 92% (median, 68%). A typical “lotus root” aspect was confirmed on OCT, consisting of multiple circular concave-edged channels of varying size, numbering between 3 and 12 depending on the slice, separated by smooth-edged septa of high luminosity without posterior attenuation. OCT also served to guide treatment, with stenting in 91% of cases. During the 17-month follow-up 91% of patients had excellent evolution. One death and 3 ACS events occurred.
Conclusions:In this large SRCT cohort, angiography had limited diagnostic value whereas OCT could be used to define disease characteristics and guide treatment of lesions inducing angina pectoris and/or silent myocardial ischemia. OCT-guided management was associated with good prognosis.
Background:The CRUSADE, ACTION and ACUITY-HORIZONS bleeding scores have been derived using Caucasian patients, and little is known about which has the better predictive ability in Chinese patients, especially for patients with STEMI.
Methods and Results:We retrospectively analyzed 2,208 consecutive STEMI patients undergoing primary PCI (PPCI). Major bleeding events were defined according to Bleeding Academic Research Consortium criteria (type 3 or 5). Predictive ability of the 3 scores was assessed using logistic regression and AUC. Unadjusted HR for 1-year death were determined on Cox proportional hazard modeling. The major bleeding rate was 2.4%. The AUC of the CRUSADE, ACTION and ACUTIY-HORIZONS models was 0.88 (95% CI: 0.84–0.92), 0.90 (95% CI: 0.87–0.94), and 0.78 (95% CI: 0.87–0.94). The calibration of the ACUTIY-HORIZONS model was not acceptable overall, or in the subgroup of access site (P<0.05). In the high-risk category, 1-year mortality was approximately 4–7-fold greater than in the low-risk category (CRUSADE: HR, 7.27; 95% CI: 3.30–16.02, P<0.001; ACTION: HR, 7.13; 95% CI: 2.19–15.41, P<0.001; ACUITY-HORIZONS: HR, 4.06; 95% CI: 1.62–10.16; P=0.003).
Conclusions:The CRUSADE and ACTION scores have greater predictive ability for in-hospital major bleeding than the ACUITY-HORIZONS risk score in Chinese STEMI patients undergoing PPCI. Mortality would increase with the transition from low- to high-risk category in 1 year.
Background:Data on outcomes of non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation drug-eluting stents (DES) are insufficient.
Methods and Results:The 2-year outcomes and predictors of target lesion revascularization (TLR) in 356 patients with 364 non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES were retrospectively evaluated. The primary outcome measure was defined as TLR. The median follow-up duration was 3.6 years (interquartile range, 2.7–4.9 years). A 2-year clinical follow-up was achieved in 99.2%. The 2-year cumulative incidence of TLR was 9.2%. Multiple stents implanted in either the main branch (adjusted odds ratio [OR] 3.01; 95% confidence interval [CI]: 1.37–6.62; P=0.006) or the side branch (adjusted OR 4.55; 95% CI: 1.99–10.4; P<0.001) and the culprit in the left anterior descending artery and its diagonal branch (adjusted OR 0.33; 95% CI: 0.15–0.75: P=0.008) were independent predictors of TLR within 2 years.
Conclusions:The 2-year outcomes for the 2-stent strategy using 2nd-generation DES in non-left main coronary bifurcation lesions were acceptable. Coronary bifurcation location in the left anterior descending artery and its diagonal branch is protective against TLR, whereas multiple stents implanted in either the main branch or the side branch was associated with TLR.
Background:A novel index of the functional severity of coronary stenosis, quantitative flow ratio (QFR), may not consider the amount of viable myocardium in prior myocardial infarction (MI) because QFR is calculated from 3D quantitative coronary angiography.
Methods and Results:We analyzed QFR (fixed-flow QFR [fQFR] and contrast-flow QFR [cQFR]) and fractional flow reserve (FFR) in prior-MI-related coronary arteries (n=75) and non-prior-MI-related coronary arteries (n=75). Both fQFR and cQFR directly correlated with FFR in the prior-MI-related coronary arteries (fQFR: r=0.84, P<0.001; and cQFR: r=0.88, P<0.001) and the non-prior-MI-related coronary arteries (fQFR: r=0.91, P<0.001; and cQFR: r=0.94, P<0.001). fQFR was significantly smaller than FFR in the prior-MI-related coronary arteries (0.73±0.14 vs. 0.79±0.11, P=0.002), but there was no significant difference between fQFR and FFR in the non-prior-MI-related coronary arteries. The value of cQFR minus FFR was significantly lower in the prior-MI-related coronary arteries compared with the non-prior-MI-related coronary arteries (−0.02±0.06 vs. 0.00±0.04, P=0.010). The diagnostic accuracy of fQFR ≤0.8 and cQFR ≤0.8 for predicting FFR ≤0.80 was numerically lower in the prior-MI-related coronary arteries compared with the non-prior-MI-related coronary arteries (fQFR: 77% vs. 87%; and cQFR: 87% vs. 92%).
Conclusions:When FFR is used as the gold standard, the accuracy of QFR for assessing the functional severity of coronary stenosis might be reduced in the prior-MI-related coronary arteries compared with non-prior-MI-related coronary arteries.
Background:Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.
Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002).
Conclusions:IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.
Background:There have been few studies on the clinical course of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan.
Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally, 293 patients with HCM were followed. The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were male. HCM-related deaths occurred in 23 patients during a mean follow-up period of 6.1±3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a total of 77 cardiovascular events that were clinically severe occurred in 70 patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox proportional hazards model analysis showed that the presence of NYHA class III at registration was a significant predictor of HCM-related deaths and that the presence of atrial fibrillation, lower fractional shortening and presence of left ventricular outflow tract obstruction in addition to NYHA class III were significant predictors of cardiovascular events.
Conclusions:In our unselected registry in an aged Japanese community, HCM mortality was favorable, but one-fifth of the patients commonly suffered from HCM-related adverse cardiovascular events during the 5-year follow-up period. Careful management of HCM patients is needed, particularly for those with the above-mentioned clinical determinants.
Background:Reference values and the characteristics of the electrocardiographic (ECG) findings using a large number of subjects are lacking for children and adolescents.
Methods and Results:A total of 56,753 digitally stored ECGs of participants in a school-based ECG screening system were obtained between 2006 and 2009 in Kagoshima, Japan. Each ECG was manually reviewed by 2 pediatric cardiologists and only ECGs with sinus rhythm were included. A final total of 48,401 ECGs from 16,773 1st (6 years old, 50% girls), 18,126 7th (12 years old, 51% girls), and 13,502 10th graders (15 years old, 52% girls) were selected. ECG variables showed differences in age and sex. However, the effects of age and sex on ECG variables such as the PQ interval, QRS voltage, and STJ segment were also different. The 98th percentile values of well-known surrogate parameters for ventricular hypertrophy in the present study were much higher than the conventional criteria.
Conclusions:The present study of a large number of pediatric subjects showed that the effects of age and sex on ECG parameters are different, and that criteria for ventricular hypertrophy should be newly determined by age and sex. We have developed reference data for STJ segment elevation for children and adolescents. These findings are useful for creating guidelines and recommendations for interpretation of pediatric ECG.
Background:Heart failure (HF) is an important complication in adults with congenital heart disease (CHD), but because only a few studies have focused on acute HF hospitalization in adults with CHD, we study aimed to define the clinical characteristics of such patients and examine the differences in acute HF between adults with CHD and acquired heart disease.
Methods and Results:We retrospectively evaluated 50 adults with CHD admitted for treatment of acute HF and compared their data with those from Japanese HF registries. Patient mean age was 37±15 years and 58% were male. In total, 86% of the patients had complex forms of CHD and 62% had undergone corrective surgery, including the Fontan procedure; 66% of patients showed right heart hemodynamic abnormality. In-hospital mortality was 4%, which was comparable to the Japanese HF registries. Survival rate was 93% at 1 year and 75% at 3 years, which was similarly poor to the rates of HF secondary to acquired heart disease.
Conclusions:We clarified the clinical characteristics of adults with CHD requiring HF hospitalization. Young adults with complex CHD were hospitalized for management of acute right HF. Short-term and mid-term outcomes were similarly poor compared with acute HF secondary to acquired heart disease.
Background:Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.
Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score- and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index.
Conclusions:Malnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients.
Background:The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e′) is an echocardiographic index of mean left ventricular (LV) filling pressure. We investigated the association between the preoperative E/e′ ratio and postoperative acute kidney injury (AKI) during off-pump coronary artery bypass surgery (OPCAB).
Methods and Results:We reviewed 585 patients who underwent OPCAB and with preserved LV ejection fraction determined by preoperative echocardiography. AKI was determined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was performed. E/e′ was also analyzed as 3 categories (E/e′ <8, 8≤E/e′≤15, and E/e′ >15) and as a continuous variable. A propensity score analysis was used to match the patients with E/e′ >15 and E/e′ ≤15. A preoperative E/e′ >15 was an independent predictor for AKI (odds ratio 3.01, 95% confidence interval 1.40–6.17). E/e′ >15 was also an independent predictor for AKI when E/e′ was analyzed with 3 categories or as a continuous variable. In the matched sample, the incidence of AKI and 1-year mortality was significantly higher in patients with E/e′ >15.
Conclusions:Among patients undergoing OPCAB with preserved LV systolic function, a preoperative E/e′ ratio >15 was an independent predictor of postoperative AKI. Measurement of the preoperative E/e′ ratio may help to assess the risk of postoperative AKI.
Background:The composition of intra-arterial clots might influence the efficacy of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute occlusions within large cerebral arteries. The aims were to assess the factors associated with blood clot structure and the impact of thromboembolus structure on MT using stent-retrievers in patients with acute large artery IS in the anterior circulation.
Methods and Results:In an observational cohort study, we studied the components of intra-arterial clots retrieved from large cerebral arteries in 80 patients with acute IS treated with MT with or without i.v. thrombolysis (IVT). Histology of the clots was carried out without knowledge of the clinical findings, including the treatment methods. The components of the clots, their age, origin and semi-quantitative graded changes in the architecture of the fibrin components (e.g., “thinning”) were compared via neuro-interventional, clinical and laboratory data. The most prominent changes in the architecture of the fibrin components in the thromboemboli were associated with IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21–10.10, P=0.02) and platelet count (OR, 2.94; 95% CI: 1.06–8.12, P=0.04).
Conclusions:In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.
Background:Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.
Methods and Results:From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14–2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03–2.11, P=0.03, respectively).
Conclusions:AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.
Background:Uncertainties remain regarding the course of existing tricuspid regurgitation (TR) after aortic valve replacement (AVR), and its long-term impact on outcome. We investigated changes in existing TR after isolated AVR for severe aortic stenosis (AS), the impact of preoperative TR on long-term outcome, and predictors of late significant TR.
Methods and Results:After excluding mild mitral regurgitation and severe TR, 226 consecutive patients undergoing isolated AVR for severe AS between 2002 and 2015 were reviewed. Patients were classified into a non-TR (none/trivial preoperative TR, n=159) and a TR group (mild/moderate preoperative TR, n=67). During follow-up (median, 4.3 years), late significant TR was more prevalent in the TR group (n=20; 35.0%) than in the non-TR group (n=13; 9.6%; HR, 10.0; 95% CI: 4.44–24.7; P<0.001). The TR group developed more right heart failure (n=3; 5% vs. no patients in the non-TR group, P=0.007), and had a decreased estimated glomerular filtration rate (relative to baseline) until 5 years postoperatively. The tricuspid annulus diameter index was an independent predictor of late significant TR development.
Conclusions:Preoperative mild or moderate TR is aggravated after isolated AVR, resulting in a high incidence of renal dysfunction and right heart failure. Concomitant tricuspid valve intervention should be considered in patients undergoing AVR for severe AS with mild or moderate TR accompanied by dilated tricuspid annulus.
Background:Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).
Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients – with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%).
Conclusions:TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.
Background:TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, β, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.
Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Cl−current and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Cl−current was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Cl−current. Phosphomimetic mutation S727D markedly decreased TMEM16A Cl−current and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice.
Conclusions:Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.
Background:The gastroepiploic artery (GEA) plays an important role in the era of multiple arterial revascularization, but spasm is a major matter of concern. The internal thoracic artery has been shown to have a strong tendency to spasm in its distal bifurcating part, whereas the segmental difference in vasoreactivity of the GEA has never been performed.
Methods and Results:The full length of the GEA obtained from 21 patients undergoing a total gastrectomy was divided into 3 sections: proximal (5 cm from the origin), middle, and distal (5 cm from the end). Concentration-response curves for vasoconstrictors (phenylephrine, prostaglandin F2α, and endothelin-1) and vasodilators (carperitide, nitroglycerin, and nifedipine) were then established using organ baths. All the vasoconstrictors and vasodilators produced concentration-dependent responses in each section. As the concentration of the vasoconstrictors increased, segments at the distal section showed a significantly greater contraction than those at the middle and proximal sections regardless of the type of vasoconstrictor. The effective concentration of drugs that caused 50% of the maximal response for endothelin-1 was significantly greater in the distal section than that in the proximal sections. No significant difference was found in vasodilators-induced relaxation.
Conclusions:The contractility increases toward to the end of the GEA. Clinically, the distal portion of the GEA should be trimmed off and not be used as an anastomotic site wherever possible.
Background:We assessed whether the occurrence of out-of-hospital cardiac arrest (OHCA) with cardiac origin increased in the disaster areas during the 3-year period after the Great East Japan Earthquake (GEJE).
Methods and Results:From the OHCA registry in Japan, yearly changes in occurrence after the GEJE were assessed by applying Poisson regression models. The risk ratio of the first year after the earthquake was significantly greater in both men and women, but the difference disappeared in the second and third years.
Conclusions:The GEJE significantly increased the occurrence of OHCA with cardiac origin in the first year after the earthquake.