Impact of New-Onset Right Bundle-Branch Block After Transcatheter Aortic Valve Replacement on Permanent Pacemaker Implantation.

BACKGROUND: A delayed and recurrent complete atrioventricular block (CAVB) is a life-threatening complication of transcatheter aortic valve replacement (TAVR). Post-TAVR evaluation may be important in predicting delayed and recurrent CAVB requiring permanent pacemaker implantation (PPI). The impact of new-onset right bundle-branch block (RBBB) after TAVR on PPI remains unknown. METHODS AND RESULTS: In total, 407 patients with aortic stenosis who underwent TAVR were included in this analysis. Intraprocedural CAVB was defined as CAVB that occurred during TAVR. A 12-lead ECG was evaluated at baseline, immediately after TAVR, on postoperative days 1 and 5, and according to the need to identify new-onset bundle-branch block (BBB) and CAVB after TAVR. Forty patients (9.8%) required PPI, 17 patients (4.2%) had persistent intraprocedural CAVB, and 23 (5.7%) had delayed or recurrent CAVB after TAVR. The rates of no new-onset BBB, new-onset left BBB, and new-onset RBBB were 65.1%, 26.8%, and 4.7%, respectively. Compared with patients without new-onset BBB and those with new-onset left BBB, the rate of PPI was higher in patients with new-onset RBBB (3.4% versus 5.6% versus 44.4%, P<0.0001). On post-TAVR evaluation in patients without persistent intraprocedural CAVB, the multivariate logistic regression analysis showed that new-onset RBBB was a statistically significant predictor of PPI compared with no new-onset BBB (odds ratio [OR], 18.0 [95% CI, 5.94-54.4]) in addition to the use of a self-expanding valve (OR, 2.97 [95% CI, 1.09-8.10]). CONCLUSIONS: Patients with new-onset RBBB after TAVR are at high risk for PPI.

Elevated Leukocyte Count and Platelet-Derived Thrombogenicity Measured Using the Total Thrombus-Formation Analysis System in Patients with ST-Segment Elevation Myocardial Infarction.

AIMS: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. METHODS: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. RESULTS: Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (ß=0.26, p=0.0065). CONCLUSIONS: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive lung cancer has a better long-term prognosis with ALK-inhibitor than other lung cancers. However, resistance to ALK-inhibitors and the control of metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK-positive lung cancer. CASE: We present the case of a 23-year-old man who developed multiple brain metastases while receiving alectinib treatment for ALK-positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained. CONCLUSION: While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK-inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research.

Ratio of left ventricular outflow tract area to aortic annulus area and complete atrioventricular block after transcatheter aortic valve replacement for aortic stenosis.

BACKGROUND: Mechanical compression of cardiac conduction system by transcatheter heart valves leads to complete atrioventricular block (CAVB) after transcatheter aortic valve replacement (TAVR). Bulging of ventricular septum in the left ventricular outflow tract (LVOT) may be associated with greater compression of conduction system, leading to irreversible CAVB. OBJECTIVE: This study aimed to investigate the association of ventricular septal bulging with TAVR-related CAVB and permanent pacemaker implantation (PPI). METHODS: Among 294 consecutive patients with severe aortic stenosis who underwent TAVR between July 2017 and February 2023, 271 were included in the analysis. As a quantitative evaluation of bulging of the ventricular septum, the ratio of LVOT area to aortic annulus area (L/A ratio) was measured at the systolic phase of computed tomography images. RESULTS: TAVR-related CAVB occurred in 64 patients (23.6%). Twenty-eight patients (10.3%) required PPI. The optimal thresholds of L/A ratio for predicting TAVR-related CAVB and PPI were 1.0181 and 0.985, respectively. Patients with less than the cut-off values had higher rate of TAVR-related CAVB and PPI than those above (28.3% vs 13.1%, p = 0.0063; 14.7% vs 4.4%, p = 0.0077, respectively). A multivariate analysis showed that L/A ratio < 1.0181 was an independent predictor of TAVR-related CAVB (odds ratio [OR] 2.65, p = 0.011), in addition to prior right bundle branch block (OR 3.76, p = 0.0005), use of a self-expanding valve (OR 1.99, p = 0.030), and short membranous septum length (OR 0.96, p = 0.037). Only L/A ratio < 0.985 was independently associated with PPI (OR 3.70, p = 0.011). CONCLUSION: Low L/A ratio is a predictor of TAVR-related CAVB and PPI.

Impact of Low-Density Lipoprotein Cholesterol Levels at Acute Coronary Syndrome Admission on Long-Term Clinical Outcomes.

AIM: Low-density lipoprotein cholesterol (LDL-C) level reduction is highly effective in preventing the occurrence of a cardiovascular event. Contrariwise, an inverse association exists between LDL-C levels and prognosis in some patients with cardiovascular diseases-the so-called "cholesterol paradox." This study aimed to investigate whether the LDL-C level on admission affects the long-term prognosis in patients who develop acute coronary syndrome (ACS) and to examine factors associated with poor prognosis in patients with low LDL-C levels. METHODS: We enrolled 410 statin-naïve patients with ACS, whom we divided into low- and high-LDL-C groups based on an admission LDL-C cut-off (obtained from the Youden index) of 122 mg/dL. Endothelial function was assessed using the reactive hyperemia index 1 week after statin initiation. The primary composite endpoint included all-cause death, as well as myocardial infarction and ischemic stroke occurrences. RESULTS: During a median follow-up period of 6.1 years, 76 patients experienced the primary endpoint. Multivariate Cox regression analysis revealed that patients in the low LDL-C group had a 2.3-fold higher risk of experiencing the primary endpoint than those in the high LDL-C group (hazard ratio, 2.34; 95% confidence interval, 1.29-4.27; p=0.005). In the low LDL-C group, slow gait speed (frailty), elevated chronic-phase high-sensitivity C-reactive protein levels (chronic inflammation), and endothelial dysfunction were significantly associated with the primary endpoint. CONCLUSIONS: Patients with low LDL-C levels at admission due to ACS had a significantly worse long-term prognosis than those with high LDL-C levels; frailty, chronic inflammation, and endothelial dysfunction were poor prognostic factors.

Efficacy of paclitaxel-carboplatin with bevacizumab as a late-line therapy for patients with advanced nonsquamous non-small cell lung cancer: A platinum rechallenge.

BACKGROUND: There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting. METHODS: Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. RESULTS: The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. CONCLUSIONS: With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.

Endothelial dysfunction predicts bleeding and cardiovascular death in acute coronary syndrome.

BACKGROUNDS: Recently, there has been increasing awareness that bleeding may lead to adverse outcomes. Endothelial dysfunction is associated with increased risk of cardiovascular and bleeding events. This study aimed to investigate the association of endothelial dysfunction with major bleeding and specific causes of death in addition to major adverse cardiovascular events in patients with acute coronary syndrome. METHODS: This single-centre retrospective observational study was conducted at a tertiary-care hospital; patients with acute coronary syndrome were included between June 2010 and November 2014 (median follow-up, 6.1 years). The reactive hyperaemia index was assessed before their discharge; reactive hyperaemia index <1.67 was defined as endothelial dysfunction. The main outcomes were the incidence of major bleeding, all-cause death, cardiovascular death, non-cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. RESULTS: Among the included 674 patients with acute coronary syndrome, 264 (39.2%) had endothelial dysfunction. Multivariable Cox-hazard analyses revealed an independent predictive value of endothelial dysfunction for major bleeding (hazard ratio 2.29, 95% confidence interval 1.17-4.48, P = 0.016) and major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43-2.89, P < 0.001). The endothelial dysfunction group patients had a 2.5-fold greater risk of cardiovascular death; however, no association was found with non-cardiovascular death. CONCLUSION: Endothelial dysfunction assessed using reactive hyperaemia index predicted future major cardiovascular event as well as major bleeding and cardiovascular death in patients with acute coronary syndrome.

Prognostic Significance of the Combination of Left Atrial Reservoir Strain and Global Longitudinal Strain Immediately After Onset of ST-Elevation Acute Myocardial Infarction.

BACKGROUND: The role of left atrial (LA) function in the long-term prognosis of ST-elevation acute myocardial infarction (STEMI) is still unclear.Methods and Results: Percutaneous coronary intervention (PCI) was performed in 433 patients with the first episode of STEMI within 12 h of onset. The patients underwent echocardiography 24 h after admission. LA reservoir strain and other echocardiographic parameters were analyzed. Follow up was performed for up to 10 years (mean duration, 91 months). The primary endpoint was major adverse cardiovascular events (MACE): cardiac death or hospitalization due to heart failure (HF). MACE occurred in 90 patients (20%) during the follow-up period. Multivariate Cox hazard analyses showed LA reservoir strain, global longitudinal strain (GLS), age and maximum B-type natriuretic peptide (BNP) were the significant predictors of MACE. Kaplan-Meier curves demonstrated that LA reservoir strain <25.8% was a strong predictor (Log rank, χ2=76.7, P<0.0001). Net reclassification improvement (NRI) demonstrated that adding LA reservoir strain had significant incremental effect on the conventional parameters (NRI and 95% CI: 0.24 [0.11-0.44]) . When combined with GLS >-11.5%, the patients with LA reservoir strain <25.8% were found to be at extremely high risk for MACE (Log rank, χ2=126.3, P<0.0001). CONCLUSIONS: LA reservoir strain immediately after STEMI onset was a significant predictor of poor prognosis in patients, especially when combined with GLS.

Mechanical dispersion combined with global longitudinal strain estimated by three dimensional speckle tracking in patients with ST elevation myocardial infarction.

Background: The role of left ventricular (LV) mechanical dispersion estimated after an ST elevation acute myocardial infarction (STEMI) remains unclear. Methods: The study participants were 208 consecutive patients (152 men, age = 72 years) presenting with STEMI for the first time who underwent primary percutaneous coronary intervention (PCI) within 12 h of STEMI onset. Within 48 h of PCI (mean = 24 h), 2D and 3D speckle-tracking echocardiography were performed. The global longitudinal strain (GLS) was calculated using 3D (3D-GLS) and 2D (2D-GLS) speckle tracking. Mechanical dispersion was defined using the standard deviation (SD) of the time to regional peak longitudinal strain (LS) for all 16 segments for both 2D-STE and 3D-STE (2D-LS-SD, 3D-LS-SD). Infarct size was estimated by Tc99m-sestamibi as the total area of < 50% of the uptake area at 2 weeks. The patients were followed up for a longer period of time (median118months) and checked for major adverse cardiac events (MACE: cardiac death, heart failure). Results: During follow-up, 55 patients experienced MACE. The cut-off values were determined using receiver operating characteristic curves. The multivariate analysis revealed that a 3D-LS-SD > 56.7 ms was a significant predictor of MACEs (hazard ratio = 1.991, 95% confidence interval 1.033-3.613, p = 0.03), but 2D-LS-SD > 58.1 ms was not an independent predictor of MACEs (hazard ratio = 1.577, 95% confidence interval 0.815-3.042, p = 0.1). Furthermore, the combination of 3D-GLS and 3D-LS-SD had accurate predictability for MACE, as shown by the Kaplan-Meier curves (log rank, χ2 = 94.1, p < 0.0001). Conclusions: LV mechanical dispersion besides 3D-GLS assessed by 3D-STE immediately after PCI can predict long-term prognosis.

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF. METHODS: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS). RESULTS: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment. CONCLUSIONS: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

Clinical Usefulness of the Serial Examination of Three-Dimensional Global Longitudinal Strain After the Onset of ST-Elevation Acute Myocardial Infarction.

BACKGROUND: Two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) can predict the prognosis. This study investigated the clinical significance of a serial 3D-STE can predict the prognosis after onset of STEMI.Methods and Results:This study enrolled 272 patients (mean age, 65 years) with first-time STEMI treated with reperfusion therapy. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Within 1 year, 19 patients who experienced major adverse cardiac events (MACE; cardiac death, heart failure requiring hospitalization) were excluded. Among the 253 patients, 248 were examined with follow-up echocardiography. The patients were followed up for a median of 108 months (interquartile range: 96-129 months). The primary endpoint was the occurrence of a MACE; 45 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 2D-global longitudinal strain (GLS) and 3D-GLS at 1-year indices were significant predictors of MACE. The Kaplan-Meier curve demonstrated that a 3D-GLS of >-13.1 was an independent predictor for MACE (log-rank χ2=165.5, P<0.0001). The deterioration of 3D-GLS at 1 year was a significant prognosticator (log-rank χ2=36.7, P<0.0001). CONCLUSIONS: The deterioration of 3D-GLS measured by STE at 1 year after the onset of STEMI is the strongest predictor of long-term prognosis.

Clinical usefulness of left ventricular outflow tract velocity time integral for heart failure with reduced ejection fraction with rapid atrial fibrillation during landiolol treatment.

BACKGROUND: Landiolol enables us to treat the patients with rapid atrial fibrillation (AF) with acute decompensated heart failure (ADHF) efficiently. We sought to determine the role of echocardiography in predicting the prognosis. METHODS: Among 314 patients, a total 115 ADHF patients with reduced ejection fraction and rapid AF were enrolled. They received landiolol treatment to decrease the heart rate (HR) to <110 bpm and change HR (ΔHR) of >20% within 24 h. The dose of landiolol was increased every 2 h; then, we performed echocardiography repeatedly, at baseline, 2 h, and 24h. We followed the patients after discharge for 180 days, and checked cardiac death and HF hospitalization as major adverse cardiac events (MACE). RESULTS: During initial hospitalization, 5 patients (4%) died. During 180 days after discharge, 19 (16%) out of 115 patients experienced MACE (2 cardiac death, 17 HF rehospitalization, 5 in-hospital death). Multivariate analysis showed that the change in left ventricular outflow tract-velocity time integral (LVOT-VTI) at 2 h was the most significant predictor for MACE (hazard ratio =1.21, 95% confidence interval: 1.10-1.83, p=0.0001). Kaplan-Meier curves demonstrated the patients with deteriorated LVOT-VTI at minimum dose landiolol suggested the high-risk patients for MACE (χ2=30.9, p<0.0001). CONCLUSIONS: During landiolol treatment, the patients with deteriorated LVOT-VTI predicted the poor prognosis. We may detect the high-risk patients by two-point echocardiography. UMIN000020084. Registered 1 November 2013 - prospective study https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000023203.

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers.

Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.

Direct Oral Anticoagulant Therapy for Isolated Distal Deep Vein Thrombosis Associated with Cancer in Routine Clinical Practice.

BACKGROUND: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for isolated distal deep vein thrombosis (IDDVT) associated with cancer in routine clinical practice remain unclear. Moreover, prior studies on prolonged therapy for IDDVT are limited. METHODS: This retrospective study enrolled 1641 consecutive patients with acute venous thromboembolism (VTE) who had received oral anticoagulant therapy, including warfarin or DOAC, between April 2014 and September 2018 in our institutions. In these patients, 200 patients with cancer-associated IDDVT were evaluated. RESULTS: Mean follow-up period was 780 ± 593 days. Major bleeding and VTE recurrence were observed in 22 (11.0%) and 11 (5.5%) patients, respectively. In multivariate analysis, statistically significant factors correlated with major bleeding were advanced cancer stage, high performance status, stomach cancer, and gallbladder cancer; those correlated with all-cause death were advanced cancer stage, high performance status, liver dysfunction, pancreatic cancer, and major bleeding. Cumulative events of major bleeding and recurrence between patients with prolonged DOAC therapy (≥90 days) and those with nonprolonged therapy were not significantly different. CONCLUSIONS: Preventing major bleeding is important because it is a significant risk factor for all-cause death. Major bleeding and recurrent events were comparable between prolonged and nonprolonged therapy.

Impact of sarcopenic obesity on long-term clinical outcomes after ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: Both low appendicular skeletal muscle index (ASMI) and specific abdominal fat composition [i.e., increased visceral to subcutaneous (V/S) fat ratio] have been associated with cardiovascular events. However, the combined impact of these 2 components on long-term outcomes remains unclear, especially in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: In 303 patients with STEMI, ASMI and V/S fat ratio were assessed using dual-energy X-ray absorptiometry and abdominal computed tomography. Based on the criteria of the Asian Working Group for Sarcopenia and median of V/S fat ratio, sarcopenic obesity (SO) pattern was defined as low ASMI with high V/S fat ratio. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for heart failure and unplanned revascularization. RESULTS: During a median follow-up of 3.9 years, primary endpoint occurred in 67 patients. Patients with an SO pattern showed significantly lower event-free survival rate compared with those without (p=0.006 by log-rank). Notably, when stratified by median age (67 years), this trend was particularly prominent in the younger-age group (p <0.001), but not significant in the older-age group (p=0.38). In the younger-age group, the multivariate analysis revealed that patients with SO pattern had a 2.97 (1.10-7.53) fold higher risk for primary endpoints compared with those without. CONCLUSIONS: Low ASMI with high V/S fat ratio, or so-called sarcopenic obesity, was associated with poor prognosis after STEMI, particularly in younger-age patients. The combined assessment of skeletal muscle with abdominal fat distribution may help stratify the risk among patients with STEMI, rather than each component alone.

Clinical Significance of Late Diastolic Tissue Doppler Velocity at 24 Hours or 14 Days After Onset of ST-Elevation Acute Myocardial Infarction.

Background: The significance of late diastolic velocity (a') obtained by tissue Doppler imaging (TDI), which reveals atrial function, in ST-elevation myocardial infarction (STEMI) remains unclear. This study evaluated the association of TDI parameters determined either immediately or 2 weeks after percutaneous coronary intervention (PCI) with long-term outcomes. Methods and Results: In all, 740 patients with first-time STEMI underwent immediate PCI (i.e., within 12 h of onset). Echocardiography was performed in 307 patients 2 weeks after onset (Group A; mean age 64 years, 249 males), in 277 patients immediately after PCI (Group B; mean age 65 years, 229 males), and in 156 patients twice (i.e., immediately and 2 weeks after PCI; Group C; mean age 65 years, 135 males). Patients were followed-up for up to 10 years (mean 81 months). The primary endpoints were cardiac death or heart failure hospitalization. Major adverse cardiovascular events (MACE) occurred in 143 patients (19%) during the follow-up period. Both univariate and multivariate Cox hazard analyses were used to determine predictors of MACE. At 24 h and 2 weeks after STEMI onset, a' and E/e' were the strongest predictors of MACE, respectively. Conclusions: TDI parameters have different implications depending on the timing of echocardiography after a first-time STEMI. Based on the results of this study, atrial dysfunction measured by TDI 24 h after STEMI onset may indicate a poor prognosis.

Association of immune-related pneumonitis with clinical benefit of anti-programmed cell death-1 monotherapy in advanced non-small cell lung cancer.

BACKGROUND: The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti-programmed cell death-1 antibody in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time-to-treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). RESULTS: CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months-not reached] vs. 3.9 months [95% CI: 3.4-5.1 months, p < 0.01]) and longer OS (27.4 [95% CI: 20.7 months-not reached] vs. 14.8 months [95% CI: 11.2-17.9 months, p = 0.003]). Most patients discontinued the immune checkpoint inhibitor (ICI) treatment when they developed CIP. Seven patients (25%) lived for more than 300 days from treatment discontinuation and did not show any long-term tumor growth after treatment discontinuation. CONCLUSION: CIP was associated with prolonged PFS and OS. Additionally, 25% of CIP patients did not show any tumor growth for long periods after treatment discontinuation. Careful management of CIP can help in obtaining the best clinical efficacy from anti-PD-1 antibody.

Global Strain Measured by Three-Dimensional Speckle Tracking Echocardiography Is a Useful Predictor for 10-Year Prognosis After a First ST-Elevation Acute Myocardial Infarction.

BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI.Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96-129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >-11.0 was an independent predictor for MACE (log-rank χ2=132.2, P<0.0001). When combined with 3D-GCS >-18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. CONCLUSIONS: Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.

Characteristics and Prognosis of Patients with Vasospastic Angina Diagnosed by a Provocation Test with Secondary Prevention Implantable Cardioverter Defibrillator.

This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

Suppression of tumor immune microenvironment via microRNA-1 after epidermal growth factor receptor-tyrosine kinase inhibitor resistance acquirement in lung adenocarcinoma.

Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death-ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR-TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR-TKI resistance and lymphocyte infiltration, before and after acquiring EGFR-TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA-1 (miR-1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR-1 on EGFR-TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8-positive T cells were significantly decreased after development of EGFR-TKI resistance. In vitro studies revealed that miR-1 significantly inhibited EGFR-TKI effect and induction of cytokines, such as C-C motif chemokine ligand 5 and C-X-C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR-1 might suppress the TIME, following development of EGFR-TKI resistance. Therefore, miR-1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR-TKI resistance.