Echocardiography has become an extension of the physical examination in cardiovascular practice. Frequently, it is used to confirm a clinical diagnostic suspicion. Another important role is to detect the underlying cardiovascular lesion to explain a patient’s symptom complex or an abnormality found on chest radiography, electrocardiography, or cardiac enzyme tests. Patients are referred to the echocardiography laboratory because of their symptoms or due to non-specific laboratory abnormalities, and echocardiographers are expected to provide a definite diagnosis or a therapeutic clue. The introduction of the matrix array transducer into clinical practice allowed the acquisition of three-dimensional (3D) datasets. 3D echocardiography (3DE) has many advantages over 2-dimensional echocardiography, such as: (1) improved visualization of the complex shapes and spatial relations between cardiac structures; (2) improved quantification of the cardiac volumes and function; and (3) improved display and assessment of valve dysfunction. 3DE is increasingly utilized during routine clinical practice. This review article is aimed to examine the current clinical utility and future directions of 3DE.
Background:This study investigated 12-lead electrocardiogram (ECG) predictors associated with atrial fibrillation (AF) or flutter (AFL), specifically whether ventricular repolarization abnormalities in surface ECG (i.e., non-specific ST-T abnormalities [NSSTTA], QT prolongation, early repolarization [ER]) were associated with the development of AF or AFL.
Methods and Results:This study included 16,793 ambulatory Koreans (mean age 48.2 years, 62.3% male) who underwent medical check-ups at Asan Medical Center in 2002 (NSSTTA, n=1,037 [6.2%]; ER, n=1,493 [8.9%]). The primary outcome was the incidence of ECG-documented AF or AFL. During follow-up, new-onset AF or AFL was documented in 334 subjects (2.0%). The incidence of AF or AFL at the 10-year follow-up was higher in patients with than without NSSTTA (3.5% vs. 1.6%; hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.28–2.50). The QT interval was associated with a higher risk of AF or AFL (HR 1.12 [95% CI 1.07–1.17] per 10 ms), and the risk was even higher in patients with multiple-region NSSTTA (HR 2.30; 95% CI 1.64–3.21) and NSSTTA with QT prolongation (HR 4.06; 95% CI 2.14–7.69). ER was not associated with a higher risk of AF or AFL (HR 1.02; 95% CI 0.71–1.46).
Conclusions:NSSTTA and QT prolongation, but not ER, were associated with a higher risk of future AF or AFL in a general ambulatory population after adjusting for parameters of atrial depolarization.
Background:Recommended rivaroxaban doses for stroke prevention in atrial fibrillation (SPAF) are 20 and 15 mg/day in patients with normal and reduced renal function, respectively, but lower doses (15 and 10 mg) have been tested and approved in Japan. It is not known whether 15 and 10 mg rivaroxaban are appropriate in other Asian populations. This study compared the anti-Factor Xa (FXa) activity of 20 and 15 mg rivaroxaban in Thai patients with normal renal function and 15 and 10 mg rivaroxaban in patients with reduced renal function.
Methods and Results:Sixty non-valvular atrial fibrillation patients receiving rivaroxaban (mean [±SD] age 69.3±9.1 years, mean creatinine clearance 59.2±22.7 mL/min) were enrolled. The anti-FXa activity of standard rivaroxaban and Japan-specific doses was measured at peak and trough concentrations. Median anti-FXa activity at peak concentrations was significantly higher for the standard than Japan-specific dose. Median anti-FXa activity measured at the trough was significantly higher for the standard dose only in those with impaired renal function. A higher proportion of patients receiving the Japan-specific rather than standard dose had anti-FXa activity at peak concentrations within the expected range (87.7% vs. 64.4%; P=0.001). One-third of those receiving the standard dose had anti-FXa activity higher than the expected range.
Conclusions:A significantly higher proportion of Thai patients receiving the Japan-specific dose of rivaroxaban had anti-FXa activity at peak concentrations within the expected range.
Background:This study aimed to assess the relationship between hospital-acquired functional decline and the risk of mid-term all-cause death in older patients undergoing transcatheter aortic valve implantation (TAVI).
Methods and Results:In total, 463 patients (mean age 85 years, interquartile range [IQR]: 82, 88) undergoing elective TAVI at Sakakibara Heart Institute between 2010 and 2018, who were followed up for 3 years, were enrolled in the study. Hospital-acquired functional decline after TAVI, which was defined by at least a 1-point decrease on the Short Physical Performance Battery before discharge compared to the preoperative score, was assessed. A total of 113 patients (24.4%) showed hospital-acquired functional decline after TAVI, and 50 (11.3%) patients died over a mean follow-up period of 1.9±0.8 years. Kaplan-Meier survival curves indicated that hospital-acquired functional decline was significantly associated with all-cause mortality (log-rank test, P=0.001). On multivariate Cox regression analysis, hospital-acquired functional decline was associated with a higher risk of all-cause mortality (OR 2.108, 95% CI 1.119–3.968, P=0.021) independent of sex, body mass index, advanced chronic kidney disease, and preoperative frailty, as assessed by the modified essential frail toolkit.
Conclusions:Hospital-acquired functional decline is associated with mid-term all-cause mortality in older patients following TAVI. Trajectory of functional status is a vital sign, and it is useful for risk stratification in older patients following TAVI.
Background:Bridge-to-decision (BTD) devices providing temporary mechanical circulatory support should be introduced to patients with advanced heart failure. This study evaluated the effectiveness and safety of a BTD device comprising an innovative extracorporeal continuous-flow temporary ventricular assist device (VAD) driven by a novel hydrodynamically levitated centrifugal flow blood pump.
Methods and Results:Nine patients, comprising 3 with dilated cardiomyopathy, 3 with fulminant myocarditis, and 3 with ischemic heart disease, and 6 males, whose mean age was 47.7±8.1 years, were enrolled into the study. Six patients had Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and 3 were profile 2. The primary endpoint was a composite of survival free from device-related serious adverse events and complications during circulatory support. Eight patients received left ventricular support, of whom 3 received concomitant right ventricular support using extracorporeal membrane oxygenation circuits, as a consequence of severe respiratory failure. One patient with fulminant myocarditis received biventricular support using the novel VAD system. After 19.0±13.5 days, 3 patients were weaned from circulatory support, because their native cardiac function recovered, and 6 patients required conversion to a durable device as a bridge-to-transplantation. One patient had non-disabling ischemic stroke episodes, and no patients died.
Conclusions:This novel extracorporeal VAD system with a hydrodynamically levitated centrifugal pump can safely and successfully bridge patients with advanced heart failure to subsequent therapeutic stages.
Background:How the time sequence of cardiopulmonary resuscitation (CPR) procedures is related to clinical outcomes in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. This study examined the impact of the time interval from collapse to start of CPR (no-flow time, NF time) and the time interval from start of CPR to implementation of extracorporeal CPR (ECPR) (low-flow time, LF time) on neurological outcomes.
Methods and Results:During the period from 2010 to 2015, we enrolled 85 patients who received ECPR. Fourteen patients (16.5%) showed favorable 30-day neurological recovery. NF time was shorter in the favorable neurological recovery group than in the unfavorable recovery group (1.4±3.0 vs. 5.2±5.8 min, P<0.05), though combined NF+LF times were similar in the 2 groups (50.1±13.2 vs. 55.1±14.8 min, P=0.25). Multivariate logistic regression analysis indicated that pupil diameter at arrival and NF time were independently associated with favorable neurological recovery. The optimal cut-off value of NF time to predict favorable neurological recovery was 5 min (area under curve: 0.70, P<0.05; sensitivity, 85.7%; specificity, 52.1%).
Conclusions:The results suggest that NF time is a better predictor than NF+LF time for neurological outcomes in OHCA patients who received ECPR, and that start of CPR within 5 min after collapse is crucial for improving neurological outcomes followed by use of ECPR.
Background:Parathyroid hormone (PTH) has been associated with cardiovascular disorders; however, it is unknown whether plasma PTH concentrations are associated with atrial fibrillation (AF) in patients with chronic kidney disease (CKD).
Methods and Results:The present cross-sectional study analyzed baseline data of 3,384 patients registered in the Fukuoka Kidney Disease Registry Study, a Japanese multicenter prospective cohort study of patients with non-dialysis-dependent CKD. The outcome was prevalence of AF, and the main risk factor was plasma intact PTH concentration. Associations between plasma intact PTH concentration quartiles (Q1–Q4, from lowest to highest) and the presence of AF were analyzed using logistic regression. In all, 185 patients had AF; 22, 34, 59, and 70 patients were in Q1, Q2, Q3, and Q4 of PTH concentrations, respectively. The prevalence of AF increased incrementally with increases in plasma intact PTH. In the logistic regression model, patients with higher plasma intact PTH concentrations (Q2–Q4) had higher adjusted odds ratios (95% confidence intervals) for the prevalence of AF relative to the reference group (Q1), namely 1.33 (0.76–2.34), 1.82 ([1.06–3.13), and 1.99 (1.08–3.64), respectively (P=0.016).
Conclusions:Higher plasma intact PTH concentrations were significantly and incrementally associated with an increased prevalence of AF in non-dialysis-dependent CKD patients.
Background:Central venous pressure (CVP) is measured to assess intravascular fluid status. Although the clinical gold standard for evaluating CVP is invasive measurement using catheterization, the use of catheterization is limited in a clinical setting because of its invasiveness. We developed novel non-invasive technique, enclosed-zone (ezCVPTM) measurement for estimating CVP. The purpose of this study was to assess the feasibility of ezCVP and the relationship between ezCVP and CVP measured by a catheter.
Methods and Results:We conducted 291 measurements in 97 patients. Linear regression analysis revealed that ezCVP was significantly correlated with CVP (r=0.65, P<0.0001). The Bland-Altman analysis showed that ezCVP had an underestimation bias of −2.5 mmHg with 95% limits of agreement of −14.1 mmHg and 9.6 mmHg for CVP (P<0.0001). The areas under the curves of receiver operating curve with ezCVP to detect the CVP ≥12 cmH2O (8.8 mmHg) and CVP >10 mmHg were 0.81 or 0.88, respectively. The sensitivity, specificity and positive likelihood ratio of ezCVP for the CVP ≥8.8 mmHg and CVP >10 mmHg were 0.59, 0.96 and 14.8 with a cut-off value of 11.9 and 0.79, 0.97 and 26.3 with a cut-off value of 12.7.
Conclusions:These findings suggest that ezCVP measurement is feasible and useful for assessing CVP.
Background:Integrated device diagnostics, Triage-HF, is useful in risk stratifying patients with heart failure (HF), but its performance for Japanese patients remains unknown. This is a prospective study of Japanese patients treated with a cardiac resynchronization therapy defibrillator (CRT-D), with a Medtronic OptiVol 2.0 feature.
Methods and Results:A total of 320 CRT-D patients were enrolled from 2013 to 2017. All received HF treatment in the prior 12 months. Following enrollment, they were followed every 6 months for 48 months (mean, 22 months). Triage-HF-stratified patients at low, medium and high risk statuses at every 30-day period, and HF-related hospitalization occurring for the subsequent 30 days, were evaluated and repeated. The primary endpoint was to assess Triage-HF performance in predicting HF-related hospitalization risk. All device data were available for 279 of 320 patients (NYHA class II or III in 93%; mean left ventricular ejection fraction, 31%). During a total of 5,977 patient-month follow-ups, 89 HF-related hospitalization occurred in 72 patients. The unadjusted event numbers for Low, Medium and High statuses were 19 (0.7%), 42 (1.6%) and 28 (4.1%), respectively. Relative risk of Medium to Low status was 2.18 (95% CI 1.23–3.85) and 5.78 (95% CI 3.34–10.01) for High to Low status. Common contributing factors among the diagnostics included low activity, OptiVol threshold crossing, and elevated night heart rate.
Conclusions:Triage-HF effectively stratified Japanese patients at risk of HF-related hospitalization.
Background:We describe our original left ventricular assist device (LVAD) speed ramp and volume loading test designed to evaluate native heart function under continuous-flow LVAD support.
Methods and Results:LVAD speed was decreased in 4 stages from the patient’s optimal speed to the minimum setting for each device. Under minimal LVAD support, patients were subjected to saline loading (body weight [kg]×10 mL in 15 min). Echocardiographic and hemodynamic data were obtained at each stage of the LVAD speed ramp and every 3 min during saline loading. Patients were divided into Recovery (with successful LVAD removal; n=8) and Non-recovery (others; n=31) groups. During testing, increased pulmonary capillary wedge pressure caused by volume loading was milder in the Recovery than Non-recovery group (repeated measures analysis of variance; group effect, P=0.0069; time effect, P<0.0001; interaction effect, P=0.0173). Increased cardiac output from volume loading was significantly higher in the Recovery than Non-recovery group (group effect, P=0.0124; time effect, P<0.0001; interaction effect, P=0.0091). Therefore, the Frank-Starling curve of the Recovery group was located upward and to the left of that of the Non-recovery group.
Conclusions:The LVAD speed ramp and volume loading test facilitates the precise evaluation of native heart function during continuous-flow LVAD support.
Background:Dyslipidemia plays a crucial role in acute coronary syndrome (ACS). Paucity of data is available concerning the effect of apolipoprotein (apo) B/A-I ratio on the severity and outcomes in diabetic patients with ACS. This study investigated these associations in a Chinese cohort undergoing percutaneous coronary intervention.
Methods and Results:In 2013, a total of 2,563 diabetic patients concomitant with ACS were included. Patients were divided into 2 groups based on the apoB/apoA-I ratio on admission: <0.63 (n=1,279, 49.9%) and ≥0.63 (n=1,284, 50.1%). Angiographic complexity and severity were determined by SYNTAX score (SS). A higher apo ratio was significantly associated with higher proportions of acute myocardial infarction (MI) and intermediate-high SS. Multivariable logistic regression analysis showed that the apo ratio was an independent factor of complicated lesions (OR 1.341, 95% confidence interval 1.039–1.730, P=0.024). Moreover, consistent results were found in the subgroups of normal concentrations of conventional lipid parameters. During a median follow-up period of 878 days, significant differences were found in periprocedural MI (1.0% vs. 2.2%, P=0.019) and total events of MI (2.0% vs. 3.3%, P=0.028). After adjusting for confounders, a high apo ratio remained independently predictive of MI, the risk of which was doubled during the periprocedural period and in the long term.
Conclusions:The ApoB/apoA-I ratio is an independent predictor for complicated lesions and future MI in patients with diabetes and ACS.
Background:Low population density may be associated with high mortality in acute myocardial infarction (AMI) patients. The purpose of this study was to investigate the effect of population density and hospital primary percutaneous coronary intervention (PCI) volume on AMI in-hospital mortality in Japan.
Methods and Results:This is a retrospective study of 64,414 AMI patients transported to hospital by ambulances. The main outcome measure was in-hospital mortality. The median population density was 1,147 (interquartile range, 342–5,210) persons/km2. There was a significant negative relationship between population density and in-hospital mortality (OR for a quartile down in population density 1.086, 95% CI 1.042–1.132, P<0.001). Patients in less densely populated areas were more often transported to hospitals with a lower primary PCI volume, and they had a longer distance to travel. By using multivariable analysis, primary PCI volume was found to be significantly associated with in-hospital mortality, but distance to hospital was not. When divided into the low- and high-volume hospitals, using the cut-off value of 115 annual primary PCI procedures, the increase in in-hospital mortality associated with low population density was observed only in patients hospitalized in the low-volume hospitals.
Conclusions:Increased in-hospital mortality related to low population density was observed only in AMI patients who were transported to the low primary PCI volume hospitals, but not in those who were transported to high-volume hospitals.
Background:Differences between resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have not been sufficiently discussed. This study aimed to investigate if there is a difference in diagnostic performance between RFR and dPR for the functional lesion assessment and to assess if there are specific characteristics for discordant revascularization decision-makings between RFR and dPR.
Methods and Results:A total of 936 intermediate lesions in 776 patients who underwent measurements of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were retrospectively studied. Physiological indices were measured from anonymized pressure recordings at an independent core laboratory. Both RFR and dPR measures were highly correlated (r=0.997, P<0.001), with equivalent diagnostic performance relative to FFR-based decision-makings measured by using a dichotomous threshold of 0.80 (accuracy, 79.7% vs. 80.1%, respectively, P=0.960). The rate of diagnostic discordance was 4.7% (44/936), with no RFR−/dPR+ lesions observed. An overall significant difference in FFR and CFR values were detected among RFR/dPR-based classifications. The prevalence of positive studies was significantly higher for RFR than dPR (54.3% vs. 49.6%, respectively, P=0.047) when using the cut-off value of 0.89.
Conclusions:Both RFR and dPR were highly correlated, but the prevalence of positive studies was significantly different. The revascularization rate may differ significantly according to the resting index used.
Background:Circulating microRNAs (miRNA) are potential prognostic biomarkers for cardiovascular disease. We aimed to identify serum miRNA as an effective predictor for coronary artery disease (CAD) events in a general population cohort.
Methods and Results:Serum miRNAs associated with CAD were determined by small RNA sequencing and quantitative RT-PCR. Further, the predictive ability of identified serum miRNAs was measured in a general population of 2,812 people. As a main outcome measure, CAD events were collected for 6 years and included acute myocardial infarction and subsequent myocardial infarction. Out of the 48 miRNA candidates, 5 miRNAs (miR-10a-5p, miR-126-3p, miR-210-3p, miR-423-3p and miR-92a-3p) showed better reliability and repeatability in serum. Then, the association of serum levels of the 5 miRNAs with CAD was validated. Furthermore, miR-10a-5p and miR-423-3p, which showed better performance, were tested in the large cohort, with a median follow up of 6.0 years. In multivariable Cox regression analysis, only miR-423-3p (P for trend<0.001) was able to precisely predict CAD events. Moreover, the addition of circulating miR-423-3p with the traditional risk factors together markedly improved the various model performance measures, including the area under the operating characteristics curve (0.782 vs. 0.806), Akaike Information Criterion (965.845 vs. 943.113) and net reclassification improvement (19.18%).
Conclusions:Circulating miR-423-3p can improve the prediction of primary CAD outcomes on the basis of a traditional risk factor model in general population.
Background:Pulmonary arterial hypertension (PAH), particularly connective tissue disease-associated PAH (CTD-PAH), is a progressive disease and novel therapeutic agents based on the specific molecular pathogenesis are desired. In the pathogenesis of CTD-PAH, inflammation, immune cell abnormality, and fibrosis play important roles. However, the existing mouse pulmonary hypertension (PH) models do not reflect these features enough. The relationship between inflammation and hypoxia is still unclear.
Methods and Results:Intraperitoneal administration of pristane, a kind of mineral oil, and exposure to chronic hypoxia were combined, and this model is referred to as pristane/hypoxia (PriHx) mice. Hemodynamic and histological analyses showed that the PriHx mice showed a more severe phenotype of PH than pristane or hypoxia alone. Immunohistological and flow cytometric analyses revealed infiltration of immune cells, including hemosiderin-laden macrophages and activated CD4+helper T lymphocytes in the lungs of PriHx mice. Pristane administration exacerbated lung fibrosis and elevated the expression of fibrosis-related genes. Inflammation-related genes such asIl6andCxcl2were also upregulated in the lungs of PriHx mice, and interleukin (IL)-6 blockade by monoclonal anti-IL-6 receptor antibody MR16-1 ameliorated PH of PriHx mice.
Conclusions:A PriHx model, a novel mouse model of PH reflecting the pathological features of CTD-PAH, was developed through a combination of pristane administration and exposure to chronic hypoxia.
Background:Patients with severe aortic stenosis (AS) might be at high risk for adverse cardiovascular events at the time of non-cardiac surgery.
Methods and Results:The current study population included 348 patients who underwent elective non-cardiac surgery under general or spinal anesthesia during the follow up of 3,815 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry. There were 187 patients with untreated severe AS at time of surgery (untreated severe AS group) and 161 patients who had undergone aortic valve replacement (AVR) before surgery (prior AVR group), including 23 patients with prophylactic AVR. The primary outcome measure was 30-day mortality after non-cardiac surgery. At 30 days after non-cardiac surgery, 8 patients (4.3%) died in the untreated severe AS group, while no patients died in the prior AVR group (P=0.008). The causes of death were cardiovascular in 6 out of 8 patients. Mortality at 30 days was higher in untreated severe AS patients with AS-related symptoms before surgery than in those without AS-related symptoms (7.2% vs. 3.1%). Higher surgical risk estimates of the non-cardiac surgery incrementally increased the risk of 30-day mortality in patients with untreated severe AS, though the difference was not statistically significant (low-risk: 0%, intermediate-risk: 4.3%, and high-risk: 6.6 %, P=0.46).
Conclusions:Symptomatic and asymptomatic severe AS might be associated with higher risk of 30-day mortality if untreated before elective intermediate- and high-risk non-cardiac surgery, while no patient with prior AVR died after elective non-cardiac surgery.
Background:NT5Egenetic mutations are known to result in calcification of joints and arteries (CALJA), and worldwide, 14 patients from 7 families have been reported.
Methods and Results:A total of 5 patients from 2 independent families with CALJA were found in Japan. Of them, 3 complained of intermittent claudication (IC), and 1 suffered from bilateral chronic limb-threatening ischemia (CLTI). Whole-exome sequencing analysis revealed an identical mutation pattern (c.G3C on the exon 1 start codon) that was unique compared withNT5Emutations reported in other countries.
Conclusions:Vascular specialists need to recognize CALJA as a rare cause of ischemic IC and CLTI.
Background:Because ST-elevation myocardial infarction (STEMI) extensively damages the heart, regenerative therapy with pluripotent stem cells such as multilineage-differentiating stress enduring (Muse) cells is required.
Methods and Results:In a first-in-human study, 3 STEMI patients with a left ventricular ejection fraction (LVEF) ≤45% after successful percutaneous coronary intervention received intravenously 1.5×107cells of a human Muse cell-based product, CL2020. The safety and efficacy on LVEF and wall motion score index (WMSI) were evaluated for 12 weeks. No adverse drug reaction was noted. LVEF and WMSI were markedly improved.
Conclusions:The first-in-human intravenous administration of CL2020 was safe and markedly improved LV function in STEMI patients.