Yuichi J. Shimada

Accuracy of Right Ventricular Volumes and Function Determined by Three-Dimensional Echocardiography in Comparison with Magnetic Resonance Imaging: A Meta-Analysis Study

BACKGROUNDnDetermining right ventricular (RV) function is challenging because of the complex anatomy of the right ventricle. Three-dimensional echocardiography (3DE) has achieved better estimation, but underestimations of volumes and ejection fraction (EF) has often been reported, and no previous study has synthesized these data. The investigators performed a meta-analysis on the bias and examined the related factors.nnnMETHODSnStudies comparing RV volumes and/or EF between 3DE and magnetic resonance imaging were eligible. A meta-analysis was performed to evaluate the systematic bias. The related bias was investigated using univariate and multivariate regression analysis.nnnRESULTSnTwenty-three studies including 807 subjects revealed underestimation of RV volumes (P < .00001) and EF (P = .03). Larger volumes and EF were associated with more underestimation. Older patient age was associated with overestimation of volumes and underestimation of EF.nnnCONCLUSIONSnThis meta-analysis found underestimation of RV volumes and EF by 3DE and factors affecting the bias. These data provide a more detailed basis for improving the accuracy of 3DE for further clinical application.

A meta-analysis and investigation for the source of bias of left ventricular volumes and function by three-dimensional echocardiography in comparison with magnetic resonance imaging.

Determining accurate left ventricular (LV) function is clinically important. Three-dimensional echocardiography (3DE) achieves better estimation than 2-dimensional echocardiography. However, underestimation of LV volumes has often been reported without a systematic attempt to synthesize these data. This meta-analysis aimed to assess the bias of 3DE in evaluating LV volumes and ejection fraction (EF) and to investigate factors affecting that bias. Studies that compared LV volumes and/or EF between 3DE and magnetic resonance imaging were eligible. Meta-analysis of 95 studies including 3,055 subjects revealed significant underestimation of LV end-systolic volume (-4.7 ml, p <0.0001) and end-diastolic volume (-9.9 ml, p <0.0001), whereas measurement for EF revealed excellent accuracy (-0.13%, p = 0.41). Meta-regression analysis for factors of systematic bias in volumetry revealed that female gender and existence of cardiac disease were associated with more underestimation, whereas use of semiautomatic tracking and matrix-array transducers counteracted the underestimation. In conclusion, by meta-analysis synthesizing many small studies, we found underestimation of LV volumes and factors affecting the systematic bias by 3DE. These data provide a more detailed basis for analyzing and improving the accuracy of 3DE, an indispensable step toward further clinical application in LV assessment.

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0u2009×u200910(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0u2009×u200910(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

Meta-Analysis of Accuracy of Left Ventricular Mass Measurement by Three-Dimensional Echocardiography

Left ventricular (LV) hypertrophy is a fundamental prognostic factor in a variety of cardiac diseases. Three-dimensional echocardiography (3DE) has achieved better estimation of LV mass than 2-dimensional echocardiography. However, significant underestimation has often been reported, and no previous study has synthesized these data. The aim of this meta-analysis was to investigate if there has been improvement in the accuracy in LV mass measurement by 3DE over time. Studies comparing LV mass between 3DE and magnetic resonance imaging were eligible. A cumulative meta-analysis was performed to investigate improvement in accuracy, followed by subgroup and meta-regression analysis to reveal factors affecting the bias. A total of 25 studies including 671 comparisons were analyzed. Studies published in or before 2004 showed high heterogeneity (I(2) = 69%) and significant underestimation of LV mass by 3DE (-5.7 g, 95% confidence interval -11.3 to -0.2, p = 0.04). Studies published from 2005 to 2007 were still heterogenous (I(2) = 60%) but showed less systematic bias (-0.5 g, 95% confidence interval -2.5 to 1.5, p = 0.63). In contrast, studies published in or after 2008 were highly homogenous (I(2) = 3%) and showed excellent accuracy (-0.1 g, 95% confidence interval -2.2 to 1.9, p = 0.90). Investigation of factors affecting the bias revealed that evaluation of cardiac patients compared to healthy volunteers led to larger bias (p <0.05). In conclusion, this meta-analysis elucidates the underestimation of LV mass by 3DE, its improvement over the past decade, and factors affecting the bias. These data provide a more detailed basis for improving the accuracy of 3DE, an indispensable step toward further clinical application.

Meta-Analysis of Prospective Randomized Controlled Trials Comparing Intracoronary Versus Intravenous Abciximab in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to improve outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention (pPCI). An earlier study reported better efficacy with intracoronary (IC) compared to intravenous (IV) administration, but this finding has not been duplicated in other studies, thus leaving a great deal of uncertainty as to the most efficacious route of administration. To investigate if IC abciximab compared to IV administration decreases mortality and major adverse cardiac events in patients with ST-segment elevation myocardial infarction who undergo pPCI, a meta-analysis was performed consisting only of prospective randomized controlled trials. Subgroup analysis was performed to investigate the source of difference in efficacy between the 2 strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC abciximab significantly reduced mortality compared to IV administration (1.5% vs 3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major adverse cardiac events were also reduced in a subgroup in which <30% of patients received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data available from relatively small but high-quality studies shows a significant mortality reduction associated using IC abciximab for pPCI compared to IV abciximab. IC abciximab in the setting of pPCI for ST-segment elevation myocardial infarction may be beneficial for patients with higher risk profiles.

Underestimation of Left Atrial Volume by Three-Dimensional Echocardiography Validated by Magnetic Resonance Imaging: A Meta-Analysis and Investigation of the Source of Bias

Background: Left atrial volume (LAV) is a fundamental prognostic factor in a variety of cardiac diseases including atrial fibrillation, heart failure, and valvular diseases. Developing a repeatable, noninvasive, and accurate method of measuring LAV is crucial. Three‐dimensional echocardiography (3DE) has achieved better estimation of LAV than two‐dimensional echocardiography. However, underestimation of LAV by 3DE has often been reported and no previous study has synthesized these data. The present study aimed at revealing existence and extent of bias in LAV measurement by 3DE and investigating related factors affecting the bias. Methods: Studies comparing LAV between 3DE and magnetic resonance imaging published before August 15, 2011 were eligible. A meta‐analysis with random effects model was performed to evaluate the systematic bias. Factors affecting the bias were investigated by univariate followed by multivariate analysis. Results: A total of 14 studies including 395 subjects revealed underestimation of LAV by 3DE (−9.4 mL; 95% confidence interval, −13.2 to −5.6mL; P < 0.00001, Fig. 2 ). Existence of cardiac disease led to more underestimation, whereas increasing the number of plane included in the analysis counteracted the underestimation (P < 0.00001 for each comparison). Conclusions: Only by synthesizing a number of small studies as a meta‐analysis could we display underestimation of LAV by 3DE and factors influencing the systematic bias. These data provide a more detailed basis for analyzing and improving the accuracy of 3DE, an indispensable step toward further clinical application in LAV assessment. (Echocardiography 2012;29:385‐390)

Relationship between proteinuria and venous thromboembolism

Nephrotic syndrome is known to cause venous thromboembolism (VTE) due to urine loss of antithrombin III and activation of the coagulation system. We hypothesized that the degree of proteinuria may predict the development of VTE. This was a retrospective case-controlled study of in-patients urban academic teaching hospital from April, 2007 to March, 2009 and who had undergone an imaging study for VTE. All radiology reports (Nxa0=xa01,647) for CT angiography of chest and Doppler sonogram of extremities were reviewed. The following data were collected: race/ethnicity, degree of proteinuria on urinalysis, serum protein and albumin levels, risk factors for VTE and renal function. The study population consisted of 284 patients with VTE and 280 age/sex matched controls. Relative to those who did not have proteinuria, patients who tested positive for protein had a 3.4-fold increased risk of VTE (odds ratio (OR) 3.4, 95% confidence interval [2.4, 5.0]). The association was unchanged when adjusted for other risk factors. Patients with proteinuria may have an increased risk of venous thromboembolism.

Risk of hypothyroidism in patients with cancer treated with sunitinib: a systematic review and meta-analysis.

Abstract Background. The multitargeted tyrosine kinase inhibitor sunitinib is used in various cancers. Clinical studies have reported a substantial variation in the incidence of hypothyroidism associated with sunitinib, without a systemic attempt to synthesize these data. Methods. We searched Medline databases for relevant clinical trials published up to May 2012. Phase II and III trials and expanded access programs of sunitinib in patients with any type of cancer that reported occurrence of hypothyroidism were eligible. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results. Incidence analysis was performed using 6678 sunitinib-treated patients from all 24 eligible trials. The incidence of all- and high-grade hypothyroidism was 9.8% (95% CI 7.3–12.4%) and 0.4% (95% CI 0.3–0.5%), respectively. A meta-analysis of seven randomized trials with 2787 subjects revealed a RR of all- and high-grade hypothyroidism of 13.95 (95% CI 6.91–28.15; p < 0.00001) and 4.78 (95% CI 1.09–20.84; p = 0.04), respectively. Subgroup analysis revealed a significantly higher incidence of all-grade hypothyroidism in patients receiving sunitinib for longer duration than in patients receiving sunitinib for shorter duration (p = 0.02). Conclusions. This meta-analysis of data available from clinical trials demonstrates that sunitinib is associated with a significant risk of developing all- and high-grade hypothyroidism. These data provide further evidence to recommend monitoring for hypothyroidism in patients receiving sunitinib.

Relation of Race (Asian, African-American, European-American, and Hispanic) to Activated Clotting Time After Weight-Adjusted Bolus of Heparin During Percutaneous Coronary Intervention

A weight-adjusted bolus of heparin (70 to 100 IU/kg) is recommended to achieve adequate anticoagulation during percutaneous coronary intervention (PCI). Proper dosing is mandatory to avoid bleeding and thrombotic complications. We investigated whether sensitivity to heparin is affected by difference in race. We performed a retrospective study with 874 consecutive PCI cases in our catheterization laboratory. The amount of initial heparin bolus (international units) per weight and subsequent activated clotting time (ACT; seconds) were obtained. Patients were divided into 4 categories based on race: Asian, African-American, European-American, and Hispanic. Multiple regression analysis was performed to validate the variables that determine the ACT. After adjusting for these variables, analysis of variance revealed the presence of a significant racial difference in ACT (p = 0.002). Successively, Student-Newman-Keuls test and Bonferroni t test revealed that Asian patients have higher ACT levels compared to other racial groups (p <0.03 for Asian vs others, p >0.26 between non-Asian groups). There was a positive relation between ACT and Asian race (p = 0.0004). Further analyses showed that Asians require 10 IU/kg less heparin per weight than other racial groups to achieve the same goal of ACT. In conclusion, decreased heparin dosing should be considered for Asian patients undergoing PCI.

Prognostic impact of terminal T wave inversions on presentation in patients with ST-Elevation myocardial infarction undergoing urgent percutaneous coronary intervention

INTRODUCTIONnTerminal T wave inversions (TTWI) indicate advanced stages of ST-elevation myocardial infarction (STEMI). The present study investigated whether TTWI predict unfavorable in-hospital outcomes in STEMI patients treated with urgent percutaneous coronary intervention (PCI).nnnMETHODSnA retrospective cohort study was performed with consecutive 188 STEMI cases undergoing urgent PCI. The primary endpoint was in-hospital major adverse cardiac event (MACE), and the secondary endpoints were ST resolution (STR) after PCI and length of stay (LOS).nnnRESULTSnTTWI on presentation were independently associated with higher incidence of in-hospital MACE (adjusted OR 2.8; 95% CI 1.1-7.0; p=0.03), inadequate STR (adjusted OR 5.5; 95% CI 2.1-14.3; p=0.01), and longer LOS (adjusted mean increase 4.1 days; 95% CI 0.3-7.9; p=0.03). TTWI predicted these outcomes better than patient-reported ischemic time or pathologic Q waves.nnnCONCLUSIONSnTTWI on presentation are an independent risk factor for poor inpatient prognosis among patients presenting with STEMI undergoing urgent PCI.