Myocardial T-Lymphocytes as a Prognostic Risk-Stratifying Marker of Dilated Cardiomyopathy　- Results of the Multicenter Registry to Investigate Inflammatory Cell Infiltration in Dilated Cardiomyopathy in Tissues of Endomyocardial Biopsy (INDICATE Study).

BACKGROUND: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13-24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up. CONCLUSIONS: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.

The Predictive Value of Changes in Body Mass Index for the Incidence of Device-Specific Infections in Patients With Implantable Left Ventricular Assist Devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) have improved quality of life and survival in patients with advanced heart failure. However, LVAD-specific infections and predicting which patients will develop infections remain challenging. This study investigated whether changes in body mass index (BMI) during hospitalization following LVAD implantation are associated with LVAD-specific infections within 1 year of implantation.Methods and Results:Patients (n=135) undergoing LVAD implantation were retrospectively divided into 2 groups based on changes in BMI from LVAD implantation to discharge: those with and without decreases in BMI. Each group was further subdivided according to baseline albumin concentrations (high [>3.7 g/dL] and low [≤3.7 g/dL]). Twenty patients developed LVAD-specific infections within 1 year. Receiver operating characteristic curve analysis resulted in a ∆BMI cut-off of less than -0.128 kg/m2. In multivariate analysis, younger patients and those with decreases in BMI had significantly higher rates of LVAD-specific infection (P=0.010 and P=0.035, respectively). LVAD-specific infection rates were significantly higher for patients with low albumin and decreases in BMI than for patients with low albumin but no decrease in BMI. CONCLUSIONS: Decreases in BMI during hospitalization after LVAD implantation and younger age were independently associated with LVAD-specific infection within 1 year. Strict patient management may be needed to avoid decreases in BMI during hospitalization after LVAD implantation, particularly in patients with low baseline albumin concentrations.

Feasibility of simultaneous 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

BACKGROUND: Simultaneous dual-tracer imaging using isotopes with close photo-peaks may benefit from improved properties of cadmium-zinc-telluride (CZT)-based scanners. METHODS: Thirty patients having undergone primary percutaneous coronary intervention for acute myocardial infarction underwent single-(99mTc-tetrofosmin (TF) or 123I-BMIPP first) followed by simultaneous 99mTc-TF /123I-BMIPP dual-tracer imaging using a Discovery NM/CT 670 CZT. The values for the quantitative gated-SPECT (QGS) and the quantitative perfusion SPECT (QPS) were assessed. RESULTS: The intra-class correlation (ICC) coefficients between the single- and dual-tracer imaging were high in all the QGS and QPS data (Summed motion score: 0.95, summed thickening score: 0.94, ejection fraction: 0.98, SRS for 99mTc-TF: 0.97/ for 123I-BMIPP: 0.95). Wall motion, wall thickening and rest scores per coronary-territory-based regions were also comparable between the single- and dual imaging (ICC coefficient > 0.91). The interrater concordance in the visual analysis for the infarction and perfusion-metabolism mismatch was significant for the global and regional left ventricle (P < 0.001). CONCLUSION: The quantitative/semi-quantitative values for global and regional left-ventricular function, perfusion, and fatty acid metabolism were closely comparable between the dual-tracer imaging and the single-tracer mode. These data suggests the feasibility of the novel CZT-based scanner for the simultaneous 99mTc-TF /123I-BMIPP dual-tracer acquisitions in clinical settings.

Mid-term predictive value of calciprotein particles in maintenance hemodialysis patients based on a gel-filtration assay.

BACKGROUND AND AIMS: Calciprotein particles (CPPs), nano-aggregates containing fetuin-A-bound calcium-phosphate, are associated with aortic stiffness and coronary calcification in maintenance hemodialysis patients. A novel gel-filtration assay can detect low-density small CPPs, which are actually a major form of circulating CPPs in vivo. We sought to investigate whether circulating CPP levels measured by gel-filtration method would accurately predict hard endpoints in maintenance hemodialysis patients. METHODS: This study used a prospective, multicenter, longitudinal, and observational design. One-hundred eight patients enrolled in this study were followed-up for about 2 years. We reported all-cause death and cardiovascular events, which included major adverse cardiac, cerebrovascular, and limb events. RESULTS: Kaplan-Meier analysis showed no significant difference between patients with the higher (>median) and lower (

Predictive value of electrocardiography-gated myocardial perfusion imaging to new-onset heart failure in patients with chronic kidney disease: findings from the J-ACCESS 3 study.

The incidence of heart failure (HF) increases in patients with chronic kidney disease (CKD). Factors that could predict patients with CKD who are at high risk for developing HF should be identified. We analysed clinical parameters and stress/rest myocardial perfusion imaging (MPI) findings derived from 499 patients with CKD by the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT 3 (J-ACCESS 3) to clarify predictors of new-onset HF. Forty-one patients with congestive HF in the J-ACCESS 3 database were followed up for three years. Multivariable Cox hazards models selected haemoglobin (hazard ratio [HR] 0.809; 95% confidence interval [CI] 0.679-0.964), summed stress score (HR 1.082; 95% CI 1.016-1.151) and left ventricular ejection fraction (HR 0.970; 95% CI 0.949-0.992) as independent predictors of new-onset HF. Haemoglobin combined with summed stress scores and ejection fraction had the greatest incremental prognostic value over any one or more combined factors (global χ2, 29.9). Anaemia, stress-induced myocardial ischaemia, and left ventricular contraction are independent predictors of risk of new-onset HF in patients with CKD. Stress/rest MPI provides additional information with which to identify patients with CKD at greater risk of new-onset HF.

Risk stratification based on J-ACCESS risk models with myocardial perfusion imaging: Risk versus outcomes of patients with chronic kidney disease.

BACKGROUND: This study aimed to validate the accuracy of major-event risk models created in the multicenter J-ACCESS prognostic study in a new cohort of patients with chronic kidney disease (CKD). METHODS AND RESULTS: Three multivariable J-ACCESS risk models were created to predict major cardiac events (cardiac death, non-fatal acute coronary syndrome, and severe heart failure requiring hospitalization): Model 1, four variables of age, summed stress score, left ventricular ejection fraction and diabetes; Model 2 with five variables including estimated glomerular filtration rate (eGFR, continuous); and Model 3 with categorical eGFR. The validation data used three-year (3y) cohort of patients with CKD (n = 526, major events 11.2%). Survival analysis of low (< 3%/3y), intermediate (3% to 9%/3y), and high (> 9%/3y)-risk groups showed good stratification by all three models (actual event rates: 3.1%, 9.9%, and 15.9% in the three groups with eGFR ≥ 15 mL/min/1.73 m2, P = .0087 (Model 2). However, actual event rates were equally high across all risk groups of patients with eGFR < 15 mL/min/1.73 m2. CONCLUSION: The J-ACCESS risk models can stratify patients with CKD and eGFR ≥ 15 mL/min/1.73 m2, but patients with eGFR < 15 mL/min/1.73 m2 are potentially at high risk regardless of estimated risk values.

Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells.

BACKGROUND: Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood. RESULTS: To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identified 3765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. We found that the nine EC types can be divided into two subgroups, corresponding to those with upper-body origins and lower-body origins, based on their epigenomic landscape. Epigenomic variations were highly correlated with gene expression patterns, but also provided unique information. Most of the deferentially expressed genes and enhancers were cooperatively enriched in more than one EC type, suggesting that the distinct combinations of multiple genes play key roles in the diverse phenotypes across EC types. Notably, many homeobox genes were differentially expressed across EC types, and their expression was correlated with the relative position of each organ in the body. This reflects the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing. CONCLUSIONS: This comprehensive analysis of epigenome characterization of EC types reveals diverse transcriptional regulation across human vascular systems. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

Clinical implications of the blood urea nitrogen/creatinine ratio in heart failure and their association with haemoconcentration.

AIMS: The blood urea nitrogen (BUN)/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF). However, the clinical impact of a high BUN/creatinine ratio at discharge with respect to renal dysfunction, neurohormonal hyperactivity, and different responsiveness to decongestion therapy remains unclear. Herein, we examined (i) the predictive value of a high BUN/creatinine ratio at discharge and (ii) its haemoconcentration-dependent effects, in patients with ADHF. METHODS AND RESULTS: The West Tokyo Heart Failure registry was a multicentre, prospective cohort registry-based study that enrolled patients hospitalized with a diagnosis of ADHF. The endpoint was post-discharge all-cause death. Based on the degree of haemoconcentration, patients (n = 2090) were divided into four subcategories. In multivariate proportional hazard analyses, a higher BUN/creatinine ratio was independently associated with higher all-cause mortality in the total population and in the extreme haemodilution (ΔHaemoglobin ≤ -0.9 g/dL) and haemoconcentration (0.8 g/dL ≤ ΔHaemoglobin) subcategories, but not in the modest haemodilution/haemoconcentration subcategories. CONCLUSIONS: A higher BUN/creatinine ratio at discharge was independently associated with higher post-discharge all-cause mortality in patients with ADHF. The predictive value of a high BUN/creatinine ratio at discharge was haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution.

Shortened acquisition time in simultaneous 99mTc-tetrofosmin and 123I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

OBJECTIVE: The use of cadmium-zinc-telluride-based scanners may increase the clinical feasibility of simultaneous dual-isotope imaging. In the current study, we sought to investigate a potential acquisition time in simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging using a Discovery NM/CT 670 cadmium-zinc-telluride. METHODS: Simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging was performed in 29 patients who had undergone primary percutaneous coronary intervention for acute myocardial infarction. Referenced images with an acquisition time of 65 s/view (16.25 min) were reframed to produce images with acquisition times of 33, 16, and 8 s/view. The values for the quantitative-gated single-photon emission computed tomography (SPECT) and the quantitative perfusion SPECT were compared. RESULTS: The quantitative-gated SPECT values for images with 33, 16, and 8 s/views showed good consistency with those for 65 s/view (the lower 95% confidence intervals for the intraclass correlation were ≥0.80). The quantitative perfusion SPECT values for Tc-tetrofosmin images with 33, 16, and 8 s/views also showed good consistency with those for 65 s/view; however, the quantitative perfusion SPECT values for I-ß-methyl-p-iodophenyl pentadecanoic acid images with an acquisition time of 8 s/view were not consistent with the reference acquisition time of 65 s/view. CONCLUSIONS: The quantitative-gated SPECT and quantitative perfusion SPECT values obtained from images with shorter acquisition times correlated with the values obtained from images with a reference acquisition time of 65 s/view; however, tracer-specific predisposition should be considered. These findings suggest that it is possible to reduce acquisition time when performing simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with the novel cadmium-zinc-telluride scanner.

Successful Bridge-to-Recovery Treatment in a Young Patient with Fulminant Eosinophilic Myocarditis: Roles of a Percutaneous Ventricular Assist Device and Endomyocardial Biopsy.

Eosinophilic myocarditis (EM) is a rare condition characterized by myocardial eosinophilic infiltration due to various underlying etiologies. The patient with EM may benefit from appropriate use of mechanical circulatory support (MCS) that acts as a bridge to myocardial recovery in response to effective immunosuppressive therapy. A 16-year-old boy presented with cardiogenic shock due to fulminant myocarditis, for which a percutaneous ventricular assist device (PVAD) was immediately inserted. Based on the histological diagnosis of EM, immunosuppressive therapy was immediately commenced, leading to improvement of left-ventricular ejection fraction (27% to 47%). The PVAD was successfully removed on day 7. Cardiac magnetic resonance imaging and dual-tracer myocardial scintigraphy suggested limited extent of irreversible myocardial damage. For fulminant EM, the short-term use of PVAD, together with immunosuppressive therapy guided by an immediate histological investigation, may be an effective bridging strategy to myocardial recovery.

Prognostic study of cardiac events in Japanese patients with chronic kidney disease using ECG-gated myocardial Perfusion imaging: Final 3-year report of the J-ACCESS 3 study.

BACKGROUND: Myocardial perfusion imaging (MPI) is considered useful for risk stratification among patients with chronic kidney disease (CKD), without renal deterioration by contrast media. METHODS AND RESULTS: The Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS 3) is a multicenter, prospective cohort study investigating the ability of MPI to predict cardiac events in 529 CKD patients without a definitive coronary artery disease. All patients were assessed by stress and rest MPI with 99mTc-tetrofosmin and data were analyzed using a defect scoring method and QGS software. Major cardiac events were analyzed for 3 years after registration. The mean eGFR was 29.0 ± 12.8 (mL/minute/1.73 m2). The mean summed stress/rest/difference (SSS, SRS, SDS) scores were 1.9 ± 3.8, 1.1 ± 3.0, and 0.8 ± 1.8, respectively. A total of 60 cardiac events (three cardiac deaths, six sudden deaths, five nonfatal myocardial infarctions, 46 hospitalization cases for heart failure) occurred. The event-free survival rate was lower among patients with kidney dysfunction, higher SSS, and higher CRP values. Multivariate Cox regression analysis independently associated SSS ≥8, eGFR <15 (mL/minute/1.73 m2), and CRP ≥0.3 (mg/dL) with cardiac events. CONCLUSIONS: Together with eGFR and CRP, MPI can predict cardiac events in patients with CKD.

Prognostic impact of reducing myocardial ischemia identified using ECG-gated myocardial perfusion SPECT in Japanese patients with coronary artery disease: J-ACCESS 4 study.

AIM: Whether myocardial ischemia identified using myocardial perfusion imaging (MPI) can be an alternative target of coronary revascularization to reduce the incidence of cardiac events remains unclear. METHODS AND RESULTS: This multicenter, prospective cohort study aimed to clarify the prognostic impact of reducing myocardial ischemia. Among 494 registered patients with possible or definite coronary artery disease (CAD), 298 underwent initial pharmacological stress 99mTc-tetrofosmin MPI before, and eight months after revascularization or medical therapy, and were followed up for at least one year. Among these, 114 with at least 5% ischemia at initial MPI were investigated. The primary endpoints were cardiac death, non-fatal myocardial infarction and hospitalization for heart failure. Ischemia was reduced ≥5% in 92 patients. Coronary revascularization reduced ischemia (n = 89) more effectively than medical therapy (n = 25). Post-stress cardiac function also improved after coronary revascularization. Ejection fraction significantly improved at stress (61.0% ±â€¯10.7% vs. 65.4% ±â€¯11.3%; p < 0.001) but not at rest (67.1% ±â€¯11.3% vs. 68.3% ±â€¯11.6%; p = 0.144), among patients who underwent revascularization. Rates of coronary revascularization and cardiac events among the 114 patients were significantly higher (13.6%, p = 0.035) and lower (1.1% p = 0.0053), respectively, in patients with, than without ≥5% ischemia reduction. Moreover, patients with complete resolution of ischemia at the time of the second MPI had a significantly better prognosis. CONCLUSIONS: Reducing ischemia by ≥5% and the complete resolution of ischemia could improve the prognosis of patients with stable CAD.

Analysis of the heart rate variability during cryoballoon ablation of atrial fibrillation.

Aims: Vagal responses such as marked bradycardia or a rapid blood pressure decrease are often observed during pulmonary vein (PV) isolation of atrial fibrillation (AF) using a cryoballoon (CB). However, the relationship between the marked vagal response and change in the heart rate variability (HRV) as a marker of the autonomic tone is not well understood. Methods and results: Fifty-four paroxysmal AF patients underwent CB ablation. The CB ablation was started from the right sided PVs in 25 patients (R group) and left sided PVs in 29 (L group). The HRV and haemodynamic status during the procedure were analysed. A vagal response was observed in 16 L group patients (61.5%) during the ablation of the different PVs (RSPV:1, RIPV:5, LSPV:15, LIPV:5), while it was observed in only 2 R group patients (9.5%) (RSPV:0, RIPV:0, LSPV:1, LIPV:1) (P = 0.0002). The HRV in the L group was significantly higher than that in the R group just after the CB ablation especially for the left sided PVs (L group vs. R group, total power of the HRV, median; RSPV, 11184.7 vs. 4360.0, P = 0.21; RIPV, 9044.3 vs. 2115.1, P = 0.01; LSPV, 21186.0 vs. 1314.2, P = 0.0002; LIPV 10265.9 vs. 1236.2, P = 0.0007). Conclusion: A marked increase in the HRV parameters was observed just after the CB ablation. An initial CB ablation of the right PVs decreased the change in the autonomic tone during the right PV ablation and subsequent left PV ablation. It prevented an excessive vagal response during the CB ablation and might be a safe procedure.

Demeanor of rivaroxaban in activated/inactivated FXa.

Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray. Upon FXa stimulation, the expressions of pro-inflammatory genes such as monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1, and interleukin-8 were maximally increased at 4 h after stimulation, and were suppressed by rivaroxaban. To confirm these results, quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) for MCP-1 were performed. FXa evoked the expression of MCP-1 maximally at 4 h after stimulation, whereas MCP-1 displayed a different temporal activation in ELISA. Interestingly, rivaroxaban inhibited both time courses of MCP-1 expression. These results suggest that rivaroxaban may not influence gene modulation in the inactivated coagulation state, but can attenuate the endothelial damage evoked by FXa and pro-inflammatory cytokine genes.

Comparison of Dopamine Transporter SPECT and 123I-MIBG Myocardial Scintigraphy to Assess Clinical Severity in Patients With Parkinson Disease.

PURPOSE: The aim of our study was to evaluate the use of dopamine transporter (DAT) SPECT and I-MIBG myocardial scintigraphy to determine the clinical severity of Parkinson disease (PD), with a focus on motor impairments affecting activities of daily living (ADLs). METHODS: Data for 65 consecutive PD patients who underwent both DAT and MIBG imaging were reviewed. Associations between imaging variables and Hoehn and Yahr (H&Y) staging or self-supportive care ratings were investigated. Univariate and multivariate regression analyses were performed to determine the factors associated with ADLs. RESULTS: After applying the exclusion criteria, 45 patients were analyzed (age, 73.1 ± 9.3 years; 23 males; H&Y stage 1: n = 12, stage 2: n = 14, stage 3: n = 10, stage 4: n = 5, and stage 5: n = 4; self-supportive care rating-dependent ADLs: n = 29). Dopamine transporter variables were significantly associated with the clinical severity of PD as assessed by H&Y staging, whereas MIBG variables were not. Dopamine transporter variables gradually decreased throughout progressive stages, whereas the MIBG variables changed only in the advanced stages. In a multivariate analysis including clinical and imaging variables, both lower DAT and MIBG uptakes were significantly associated with dependent ADL status (P = 0.028 and 0.034, respectively). CONCLUSIONS: In patients with PD, DAT SPECT and MIBG myocardial scintigraphy were associated with ADL status; DAT SPECT was a stronger indicator of severity than MIBG myocardial scintigraphy in the early and middle stages.

A Novel Index Using Ankle Hemodynamic Parameters to Assess the Severity of Peripheral Arterial Disease: A Pilot Study.

In peripheral arterial disease (PAD) of the lower extremities, the presence of flow-limiting stenoses can be objectively detected by the ankle-brachial index (ABI). However, the severity of ischemic symptoms is not necessarily associated with the ABI value. Atherosclerotic plaque in lower extremity PAD induces ankle arterial stiffness and reduces ankle vascular resistance, which may decrease ankle blood flow and cause ischemic symptoms. We hypothesized that the ankle hemodynamic index (AHI), defined as the ratio of ankle arterial stiffness to ankle vascular resistance, could be used to assess the blood supply deficiency in a diseased lower limb in patients with PAD. The 85 consecutive patients with PAD who were retrospectively analyzed in this study had Rutherford grade 1 to grade 6 ischemia diagnosed as PAD and significant stenotic lesions (>50% diameter stenosis) of the lower extremity on contrast angiography. The AHI was calculated as the product of the ankle pulse pressure and the ratio of heart rate to ankle mean arterial pressure (ankle pulse pressure × heart rate/ankle mean arterial pressure). The Rutherford grade was significantly correlated with the AHI (r = 0.50, P < 0.001), but not with the ABI (r = 0.07, P = 0.52). Multiple ordinal regression analysis showed that anemia (odds ratio 0.66, P = 0.002) and AHI (odds ratio 1.04, P = 0.02) were independently associated with Rutherford grade. Our study shows that AHI, a novel parameter based on the ABI measurement, is well correlated with ischemic symptoms, and may be a useful means to assess the arterial blood supply of the lower extremities of patients with PAD.

Cardiac magnetic resonance imaging-based myocardial strain study for evaluation of cardiotoxicity in breast cancer patients treated with trastuzumab: A pilot study to evaluate the feasibility of the method.

BACKGROUND: Trastuzumab, used to treat breast cancer overexpressing human epidermal growth factor receptor 2, may be cardiotoxic. Cardiac magnetic resonance (CMR) imaging with myocardial strain studies has been used to evaluate subclinical biventricular myocardial changes, however, its clinical utility during chemotherapy has not been evaluated. METHODS: The clinical outcomes, CMR and cardiac biomarkers of 9 women aged 62.3 ± 12.6 years with early or locally advanced breast cancer were evaluated at baseline, and at 3, 6 and 12 months after the initiation of trastuzumab. RESULTS: None of the patients developed heart failure or elevated serum cardiac biomarkers. Global left ventricular (LV) peak systolic longitudinal and circumferential strains were significantly decreased at 6 months (longitudinal strains, -21.1 ± 1.7% [baseline] vs. -19.5 ± 1.0% [6 months], p = 0.039, and circumferential strains, -23.4 ± 1.8% [baseline] vs. -21.6 ± 2.5% [6 months], p = 0.036). These changes were analogous to those observed in the LV ejection fraction. Right ventricular (RV) free wall peak systolic circumferential strains were decreased at 6 months (-20.9% ± 2.4% [baseline] vs. -19.1% ± 2.3% [6 months], p = 0.049), whereas RV longitudinal strains and ejection fraction remained unchanged. The LV longitudinal strain was the most reproducible of the 4 peak strain parameters. CONCLUSIONS: The LV longitudinal and circumferential strains measured by CMR decreased during trastuzumab therapy, although their predictive value for later heart failure or association with RV parameters was not determined. These techniques may be a useful means of diagnosing and monitoring trastuzumab-related cardiotoxicity.

Clinical implications of pleural effusion in patients with acute type B aortic dissection.

BACKGROUND: Pleural effusion may complicate acute Stanford type B aortic dissection (ABAD). AIMS: To identify the relationships between the quantity and side of the pleural effusion, biomarkers and outcomes in patients with ABAD. METHODS: We undertook a retrospective review of 105 patients with ABAD. Their demographics, the data on admission and during hospital stay, the volume of pleural effusion calculated from the area on computed tomography images and clinical outcomes were analysed. RESULTS: The median estimated peak volume (median 6.7 days after onset) was 129 ml (63-192, range 26-514 ml) on the left and 11 ml (6-43, range 2-300 ml) on the right. On univariate analysis, the volume of bilateral effusions was associated with anaemia, hypoalbuminaemia and inflammatory markers, whereas the volume of left-sided effusions was associated with older age, low diastolic blood pressure and maximum aortic diameter. Multivariate analysis revealed that hypoalbuminaemia was independently associated with bilateral effusion volume ( P<0.001), while maximum aortic diameter was associated with left-sided effusion volume ( P=0.019). A greater volume of bilateral plural effusion was associated with longer intensive care unit stay. CONCLUSIONS: Larger bilateral pleural effusions in patients with ABAD were associated with hypoalbuminaemia and potentially with anaemia and inflammation, and may increase the length of intensive care unit stay. Left-sided effusion volume appears to be influenced by the nature of the aortic dilatation. Multiple mechanisms may underpin the development of pleural effusion in ABAD, and are likely to influence clinical outcomes.