A case of late-onset bleeding from an intercostal artery pseudoaneurysm after hemostasis using soft coagulation.

BACKGROUND: The use of soft coagulation is becoming common in thoracic surgery. Soft coagulation provides rapid hemostasis from small vessels during surgery by dehydrating tissue and denaturing proteins, without burning the tissue. CASE PRESENTATION: A 68-year-old man, with a history of right lower lobectomy 3 years prior, underwent a partial resection of the right upper lobe for a pulmonary nodule suspicious for secondary lung cancer. During the surgery, dissection of the adhesion caused a bleeding from the 6th intercostal artery, and hemostasis was achieved using soft coagulation (some degree of tissue carbonization was noticed at later mortality and morbidity conference). He experienced hemoptysis at postoperative day 18 and was transferred to our hospital. Contrast-enhanced CT scan revealed bleeding from the pseudoaneurysm of the 6th intercostal artery. Embolization was performed by angiography to stop the bleeding. CONCLUSIONS: We experienced a case of late-onset bleeding from a pseudoaneurysm related to soft coagulation hemostasis. Lessons learned from this patient are that additional hemostasis, such as ligation, would be considered for small arteries after hemostasis has been achieved by soft coagulation, especially when some degree of tissue carbonization is suspected.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion.

INTRODUCTION: Approximately 10% of mutations in the EGFR gene in NSCLC are in-frame insertions in exon 20 (X20ins). These tumors usually do not respond to conventional EGFR tyrosine kinase inhibitors (TKIs). Several novel EGFR TKIs active for X20ins are in clinical development, including mobocertinib, which was recently approved by the U.S. Food and Drug Administration. However, acquired resistance during treatment with these TKIs still occurs as in the case of EGFR TKIs of earlier generations. METHODS: We chronically exposed murine pro-B-cell line cells transduced with the five most common X20ins (A763_Y764insFQEA, V769_D770insASV, D770_N771insSVD, H773_V774insNPH and H773_V774insH) to mobocertinib in the presence of N-ethyl-N-nitrosourea and searched for secondary EGFR mutations. We evaluated the efficacies of several EGFR X20ins inhibitors, including zipalertinib and sunvozertinib, against cells with acquired resistant mutations. RESULTS: All secondary mutations resulting in acquired resistance to mobocertinib were exclusively C797S in insFQEA and insSVD. However, in the case of other X20ins (insASV, insNPH, and insH), T790M or C797S secondary mutations contributed to acquired resistance to mobocertinib. The emergence of T790M was more frequent in cells treated with lower drug concentrations. Sunvozertinib exhibited good activity against resistant cells with T790M. Cells with C797S were refractory to all EGFR TKIs, except for erlotinib, which was active for insFQEA with C797S. CONCLUSIONS: T790M or C797S, depending on the original X20ins mutations, conferred acquired resistance to mobocertinib. Sunvozertinib may be the treatment of choice for patients with tumors resistant to mobocertinib because of T790M.

Recent Advances in Perioperative Immunotherapies in Lung Cancer.

Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions.

Non-contact and direct electrocaloric effect measurement for high-throughput material screening.

A non-contact and direct electrocaloric effect (ECE) measurement system was developed for rapid ECE measurement. The ECE of ferroelectric materials was measured directly using two measurement methods, namely, the constant heating rate method (CH method) and one-dimensional temperature gradient method (1D method), with the measurement system. The CH method continuously measures the ECE while gently heating the sample, and it can evaluate the performance of the sample more quickly than conventional methods that measure the ECE at steady state. The 1D method directly measures the ECE using a 1D temperature distribution applied to the sample. This method can measure the temperature dependence of the ECE faster than the CH method. The measurement system achieved a high signal-to-noise ratio, and the temperature dependence of the ECE measured by the two methods was consistent. The proposed measurement system and methods enable promising candidate materials for electrocaloric cooling systems to be screened more rapidly than when using conventional approaches.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

The genotype-dependent phenotypic landscape of quinoa in salt tolerance and key growth traits.

Cultivation of quinoa (Chenopodium quinoa), an annual pseudocereal crop that originated in the Andes, is spreading globally. Because quinoa is highly nutritious and resistant to multiple abiotic stresses, it is emerging as a valuable crop to provide food and nutrition security worldwide. However, molecular analyses have been hindered by the genetic heterogeneity resulting from partial outcrossing. In this study, we generated 136 inbred quinoa lines as a basis for the molecular identification and characterization of gene functions in quinoa through genotyping and phenotyping. Following genotyping-by-sequencing analysis of the inbred lines, we selected 5,753 single-nucleotide polymorphisms (SNPs) in the quinoa genome. Based on these SNPs, we show that our quinoa inbred lines fall into three genetic sub-populations. Moreover, we measured phenotypes, such as salt tolerance and key growth traits in the inbred quinoa lines and generated a heatmap that provides a succinct overview of the genotype-phenotype relationship between inbred quinoa lines. We also demonstrate that, in contrast to northern highland lines, most lowland and southern highland lines can germinate even under high salinity conditions. These findings provide a basis for the molecular elucidation and genetic improvement of quinoa and improve our understanding of the evolutionary process underlying quinoa domestication.

Changes of echocardiographic parameters in primary mitral regurgitation and determinants of symptom: an assessment from the Asian Valve Registry data.

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Clinical Usefulness of Pressure Recovery Adjustment in Patients with Predominantly Severe Aortic Stenosis: Asian Valve Registry Data.

BACKGROUND: Adjustment for pressure recovery (PR) may reconcile discrepancies in pressure gradients measured by Doppler echocardiography and direct catheterization in patients with mild to moderately severe aortic stenosis (AS). The aim of this study was to evaluate whether PR adjustment is useful in a large cohort of predominantly patients with severe AS. METHODS: Data from 697 patients (mean age 70 ± 11 years) in the Asian Valve Registry with a mean aortic valve area (AVA) of 0.8 ± 0.3 cm2 and a mean gradient of 46 ± 21 mm Hg were analyzed. PR-adjusted AVAs were calculated using validated equations. The primary outcome included aortic valve replacement, all-cause mortality, and hospitalization for heart failure during the median follow-up period of 2.9 years. RESULTS: Before PR adjustment, 521 patients showed AVA values of ≤1.0 cm2, and after PR adjustment, 129 (24.8%) were reclassified to moderate AS with a mean AVA of 1.1 ± 0.1 cm2. PR adjustment decreased the frequency of low-gradient severe AS (AVA ≤ 1.0 cm2 and mean gradient < 40 mm Hg) from 22.4% (156 of 697) to 10.2% (71 of 697). Most reclassification (>95%) occurred in patients with aortic dimensions < 3.5 cm, mean gradients < 60 mm Hg, or AVAs between 0.8 and 1.0 cm2. Patients with reclassification to moderate AS after PR adjustment showed higher 4-year clinical event-free survival rates (46.2 ± 4.9% vs 14.6 ± 2.1% in patients with severe AS after PR adjustment, P < .001). Cox regression analysis showed that reclassification after PR adjustment had additive value to predict the primary outcome (hazard ratio, 0.678; 95% CI, 0.467-0.985; P = .041) and aortic valve replacement (hazard ratio, 0.663; 95% CI, 0.440-0.998; P = .049). CONCLUSIONS: Clinically relevant PR frequently occurs in patients with moderate to severe AS. PR adjustment has prognostic implications, and accurate classification of severe AS can help prevent discordant AS grading.

Insights into the mechanism of paradoxical low-flow, low-pressure gradient severe aortic stenosis: association with reduced O2 consumption by the whole body.

The mechanism of reduced stroke volume index (SVi) in paradoxical low-flow, low-pressure gradient (PLFLPG) aortic stenosis (AS) remains unclarified. Guyton et al. ( 21 ) demonstrated that SVi is determined by whole body O2 consumption (V̇o2) in many subjects, including patients with heart disease. We hypothesized that reduced SVi in PLFLPG AS is associated with reduced V̇o2 by the whole body. This study investigated the relationship between V̇o2, SVi, and AS severity in patients with AS to examine the association between reduced V̇o2 and PLFLPG AS. In 59 patients (24 men and 35 women, mean age: 78 ± 7 yr old) with severe AS, SVi, AS severity, and type were evaluated by echocardiography, and V̇o2 was measured by the fraction of O2 in expired gases. SVi and V̇o2 were significantly decreased in 20 patients with PLFLPG AS compared with 39 patients with non-PLFLPG AS (30 ± 4 vs. 41 ± 7 ml/m2 and 2.4 ± 0.5 vs. 3.0 ± 0.5 ml·min-1·kg-1, respectively, P < 0.01). The SVi-to-V̇o2 ratio was not different between the two groups (13.1 ± 2.6 vs. 13.6 ± 2.1, not significant). SVi was independently correlated with V̇o2 ( r = 0.74, P < 0.01) but not with the aortic valve area index. Categorized PLFLPG AS was also significantly associated with reduced V̇o2 ( P < 0.001). PLFLPG AS is associated with reduced V̇o2 by the whole body, which may offer insights into the mechanism of PLFLPG AS. NEW & NOTEWORTHY Paradoxical low-flow, low-pressure gradient severe aortic stenosis (PLFLPG AS) is an important and problematic subtype, and its central pathophysiology with reduced stroke volume is yet to be clarified. We hypothesized and subsequently clarified that reduced stroke volume in PLFLPG AS is associated with reduced O2 consumption by the whole body. This study suggests important insights into the mechanism of PLFLPG AS and may further promote studies to investigate further mechanisms and novel treatment.

Possible mechanism of late systolic mitral valve prolapse: systolic superior shift of leaflets secondary to annular dilatation that causes papillary muscle traction.

Progressive superior shift of the mitral valve (MV) during systole is associated with abnormal papillary muscle (PM) superior shift in late systolic MV prolapse (MVP). The causal relation of these superior shifts remains unclarified. We hypothesized that the MV superior shift is related to augmented MV superiorly pushing force by systolic left ventricular pressure due to MV annular dilatation, which can be corrected by surgical MV plasty, leading to postoperative disappearance of these superior shifts. In 35 controls, 28 patients with holosystolic MVP, and 28 patients with late systolic MVP, the MV coaptation depth from the MV annulus was measured at early and late systole by two-dimensional echocardiography. The PM tip superior shift was monitored by echocardiographic speckle tracking. MV superiorly pushing force was obtained as MV annular area × (systolic blood pressure - 10). Measurements were repeated after MV plasty in 14 patients with late systolic MVP. Compared with controls and patients with holosystolic MVP, MV and PM superior shifts and MV superiorly pushing force were greater in patients with late systolic MVP [1.3 (0.5) vs. 0.9 (0.6) vs. 3.9 (1.0) mm/m2, 1.3 (0.5) vs. 1.2 (1.0) vs. 3.3 (1.3) mm/m2, and 487 (90) vs. 606 (167) vs. 742 (177) mmHg·cm2·m-2, respectively, means (SD), P < 0.001]. MV superior shift was correlated with PM superior shift ( P < 0.001), which was further related to augmented MV superiorly pushing force ( P < 0.001). MV and PM superior shift disappeared after surgical MV plasty for late systolic MVP. These data suggest that MV annulus dilatation augmenting MV superiorly pushing force may promote secondary superior shift of the MV (equal to late systolic MVP) that causes subvalvular PM traction in patients with late systolic MVP. NEW & NOTEWORTHY Late systolic mitral valve prolapse (MVP) is associated with mitral valve (MV) and papillary muscle (PM) abnormal superior shifts during systole, but the causal relation remains unclarified. MV and PM superior shifts were correlated with augmented MV superiorly pushing force by annular dilatation and disappeared after surgical MV plasty with annulus size and MV superiorly pushing force reduction. This suggests that MV annulus dilatation may promote secondary superior shifts of the MV (late systolic MVP) that cause subvalvular PM traction.

Comparison between characteristics of severe and very severe aortic stenosis.

OBJECTIVES: Patients with very severe aortic stenosis (AS) have extremely poor clinical outcomes even if they are asymptomatic compared to those with severe AS, but the clinical and echocardiographic characteristics of patients with very severe AS remain unclear. METHODS: The Asian Valve Registry is a prospective, multicenter, multinational registry for the study and identification of the incidence, natural course, clinical outcomes, and prognostic factors for patients with significant AS at 9 centers in Asian countries. Severe AS was observed in 367 of 1066 patients with AS, and 212 were classified as very severe AS, defined as a peak aortic valve velocity ≥5.0 m/s or a mean aortic valve gradient ≥60 mm Hg. RESULTS: The prevalence of NYHA functional class II-IV among patients with very severe AS was significantly higher than that among patients with severe AS (67.9% vs 51.5%, P < .001). As for echocardiographic parameters, it was noteworthy that left ventricular mass index (LVMI) and left atrial volume index (LAVI) for patients with very severe AS were significantly larger than those for patients with severe AS (LVMI: 145.1 ± 36.4 g/m2 vs 119.2 ± 32.1 g/m2 , P < .0001; LAVI: 56.1 ± 24.6 mL/m2 vs 49.8 ± 22.6 mL/m2 , P = .002). Moreover, multivariate logistic regression analysis showed that LVMI was the only independently associated with NYHA functional class II-IV in patients with very severe AS. CONCLUSIONS: Our findings may well have clinical implications for better management of patients with AS and lead to better understanding of poor outcomes for patients with very severe AS.

Relationships Between Periventricular Epicardial Adipose Tissue Accumulation, Coronary Microcirculation, and Left Ventricular Diastolic Dysfunction.

BACKGROUND: Obesity is related to left ventricular (LV) diastolic dysfunction, although its pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) is an ectopic fat with paracrine effects on coronary circulation and myocardium. We hypothesized that left ventricle-specific (periventricular) EAT may deteriorate diastolic function by impairing coronary microcirculation. METHODS: In protocol 1, 74 patients without obstructive narrowing of the left anterior descending artery on multidetector computed tomography (MDCT) underwent coronary flow reserve (CFR) examination to evaluate the relationship between EAT and coronary microcirculation. In protocol 2, 372 patients who underwent both MDCT and serial transthoracic Doppler echocardiographic (TTDE) examinations were enrolled to investigate the impact of periventricular EAT on changes in diastolic function. EAT volume was measured by MDCT. CFR and diastolic function were assessed by TTDE. Deterioration of LV diastolic function was defined as a ≥ 20% decrease in early diastolic mitral annular velocity. RESULTS: CFR was significantly correlated with periventricular EAT volume (r = -0.37; P = 0.001), but not with total EAT volume (r = -0.21; P = 0.071). Periventricular EAT volume (P = 0.010) was significantly associated with CFR independent of cardiovascular risk factors. Among the 372 patients who had serial TTDE examinations, the frequency of deteriorated LV diastolic function was lowest in the lower tertile of periventricular EAT, intermediate in the middle tertile, and highest in the upper tertile (12.9%, 21.0%, and 25.8%, respectively; P = 0.037). Age, diabetes mellitus, and periventricular EAT volume were significantly associated with deterioration of LV diastolic function (all P < 0.05). CONCLUSIONS: This study demonstrated the close association of periventricular EAT with impaired CFR and deteriorated LV diastolic function.

Cellular force assay detects altered contractility caused by a nephritis-associated mutation in nonmuscle myosin IIA.

Recent progress in understanding the essential roles of mechanical forces in regulating various cellular processes expands the field of biology to one where interdisciplinary approaches with engineering techniques become indispensable. Contractile forces or contractility-inherently present in proliferative cells due to the activity of ubiquitous nonmuscle myosin II (NMII)-are one of such mechano-regulators, but because NMII works downstream of diverse signaling pathways, it is often difficult to predict how the inherent cellular forces change upon perturbations to particular molecules. Here, we determine whether the contractility of individual cells is upregulated or downregulated based on an assay analyzing specific deformations of silicone gel substrates. We focus on the effect of mutations in the human MYH9 gene that encodes NMIIA, which have been implicated in the pathogenesis of various diseases including nephritis. Our assay equipped with a high-throughput data analysis capability reveals that a point mutation of E1841K but not I1816V significantly reduces the magnitude of the endogenous forces of human embryonic kidney (HEK293) cells. Given the increasingly recognized roles of the endogenous forces as a critical mechano-regulator as well as that no apparent morphological changes were induced to cells even by introducing the mutations, our findings suggest a possibility that the detected reduction in the force magnitude at the individual cellular level may underlie the pathogenesis of the kidney disease.

Insufficient Leaflet Remodeling in Patients With Atrial Fibrillation: Association With the Severity of Mitral Regurgitation.

BACKGROUND: The relationship between annular dilatation caused by atrial fibrillation (AF) and mitral regurgitation (MR) remains controversial. We hypothesized that the small ratio of total leaflet area/annulus area (TLA/AA), reflecting insufficient leaflet remodeling to annular dilatation, is a main component of MR in patients with AF. METHODS AND RESULTS: Three-dimensional transesophageal echocardiographic data of the mitral valve were analyzed in 28 AF patients with moderate or severe MR (MR group), age- and sex-matched 56 AF patients with mild or less MR (non-MR group), and 16 control subjects. AA was significantly greater in both the MR (645±126 mm2/m2, P<0.001) and non-MR groups (568±121 mm2/m2, P=0.001) compared with control subjects (444±108 mm2/m2). However, TLA/AA was significantly smaller in the MR (1.29±0.10, P<0.001), but not in the non-MR group (1.65±0.24, P>0.99), compared with control subjects (1.70±0.29). In linear regression analysis, TLA/AA was inversely associated with the effective regurgitant orifice (r=-0.73, P<0.001). The area under the receiver-operating-characteristics curve of TLA/AA was significantly greater than that of AA (0.95 versus 0.72, P<0.001). Multivariable analysis revealed that small TLA/AA (P<0.001) was independently associated with significant MR, while AA was not (P=0.26). CONCLUSIONS: In patients with AF, insufficient leaflet remodeling to annular dilatation, rather than crude annular dilatation, was strongly associated with the severity of MR.

High-sensitive cardiac troponin T as a novel predictor for recurrence of atrial fibrillation after radiofrequency catheter ablation.

AIMS: We aimed to determine whether elevated serum high-sensitive cardiac troponin T (hs-TnT) levels predict atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). METHODS AND RESULTS: We included 125 consecutive patients with AF (paroxysmal, n = 79; persistent, n = 46) who underwent first-time PVI. Serum hs-TnT, high-sensitive C-reactive protein (hs-CRP), atrial natriuretic peptide, and plasma B-type natriuretic peptide levels were measured in venous samples collected before PVI. Elevated hs-TnT was diagnosed in patients with levels ≥0.014 µg/L. All patients underwent multidetector computed tomographic examinations before PVI to measure left atrial volume (LAV) and left ventricular (LV) mass, which were indexed to body surface area. Arrhythmia recurrence was defined as AF/atrial tachycardia episodes lasting for ≥30 s after a 2-month blanking period from the PVI procedure. Elevated hs-TnT levels were observed in 22 (17.6%) patients. Age, diabetes mellitus, LV mass index, estimated glomerular filtration rate, and hs-CRP were independently associated with serum hs-TnT levels (all P < 0.05). During a mean follow-up of 12.9 ± 8.5 months after a single PVI procedure, the clinical recurrence rate was 33% (n = 41). Multivariate Cox proportional hazard analysis revealed that a greater LAV index (P = 0.01) and elevated serum hs-TnT level (P = 0.01) were significant predictors of AF recurrence after PVI. CONCLUSION: This study demonstrated that elevated serum hs-TnT levels are associated with AF recurrence independent of traditional risk factors and left atrial enlargement.

Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5'-triphosphate infusion.

BACKGROUND: Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. METHODS: Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180µg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. RESULTS: In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). CONCLUSION: Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure.

Left Atrial Remodeling in Segmental vs. Global Mitral Valve Prolapse　- Three-Dimensional Echocardiography.

BACKGROUND: Segmental and global mitral valve prolapse (MVP) comprise 2 representative phenotypes in this syndrome. While mitral regurgitation (MR) severity is a major factor causing left atrial (LA) remodeling in MVP, prominent mitral valve (MV) annulus dilatation in global MVP may specifically cause inferiorly predominant LA remodeling. We compared MV annulus and LA geometry in patients with segmental and global MVP.Methods and Results:LA volume as well as inferior, middle, and superior LA cross-sectional areas (CSA) were measured on 3-D echocardiography in 20 controls, in 40 patients with segmental MVP, and in 18 with global MVP. On multivariate analysis, MR severity was primarily associated with LA dilatation in segmental MVP (P<0.001), while MV annular dilatation was primarily associated with LA dilatation in global MVP (P<0.001). Although there was no regional predominance in LA dilatation in segmental MVP, inferior predominance of LA dilatation was significant in global MVP (increase in inferior, middle, and superior LA-CSA relative to mean of the controls: +220±70% vs. +171±55% vs. +137±37%, P<0.001). CONCLUSIONS: LA remodeling in segmental and global MVP is considerably different regarding its association with MR volume or MV annular dilatation and its regional predominance. While MR volume may mainly contribute to LA remodeling in segmental MVP, MV annular dilatation seems to have an important role in LA remodeling in global MVP. (Circ J 2016; 80: 2533-2540).

Basal Left Ventricular Dilatation and Reduced Contraction in Patients With Mitral Valve Prolapse Can Be Secondary to Annular Dilatation: Preoperative and Postoperative Speckle-Tracking Echocardiographic Study on Left Ventricle and Mitral Valve Annulus Interaction.

BACKGROUND: Prominent mitral valve (MV) annular dilatation with only modest left ventricular (LV) dilatation in patients with MV prolapse (MVP) suggests predominant dilatation in adjacent basal LV, which may augment regional wall tension and attenuate contraction by Laplace's law. We hypothesized that MV annular dilatation in patients with MVP is associated with the basal predominance of LV dilatation and attenuated contraction, which can be altered by surgical MV plasty with annulus reduction. METHODS AND RESULTS: Echocardiography with speckle-tracking analysis to assess regional cross-sectional short-axis area and longitudinal contraction (strain) of basal, middle, and apical LV was performed in 30 controls and 130 patients with MVP. The basal value/averaged middle and apical values (B/M·A ratio) of LV cross-sectional area and strain were obtained. Patients with MVP showed significantly greater MV annular area (6.4±1.6 versus 3.7±0.6 cm2/m2), increased B/M·A LV area ratio (2.4±0.5 versus 1.8±0.2), and reduced B/M·A LV strain ratio (0.83±0.14 versus 0.96±0.09) than controls (P<0.001). Multivariable analyses identified that MV annular dilatation was independently associated with increased B/M·A LV area ratio (ß=0.60, P<0.001), which was associated with reduced B/M·A LV strain ratio (ß=-0.32, P<0.001). In 35 patients with MVP, B/M·A LV area and strain ratio significantly altered after surgical MV plasty with annulus reduction (2.5±0.5-1.8±0.3 and 0.73±0.10-0.89±0.17, P<0.001, respectively). CONCLUSIONS: In patients with MVP, MV annular dilatation was associated with the basal predominance of LV dilatation and reduced contraction, which can be altered by surgical MV plasty with annulus reduction, suggesting unfavorable influence from MV annular dilatation on basal LV.