This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking-derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter ...population of patients with severe functional tricuspid regurgitation.
Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown.
Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models.
Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (-16%) had significantly reduced event-free survival compared with those with RVFWLS <median (log-rank p < 0.001). By Cox multivariable regression modeling, RVFWLS was associated with increased risk-of-death after adjustment for clinical and imaging risk factors, including RV size and ejection fraction (hazard ratio: 1.14 per %; p < 0.001). Addition of RVFWLS in this model resulted in significant improvement in the global chi-square (31 to 78; p < 0.001).
CMR feature-tracking-derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.
Background Filtering facepiece respirators are the most common respirator worn by US health care and industrial workers, yet little is known on the physiologic impact of wearing this protective ...equipment. Methods Twenty young, healthy subjects exercised on a treadmill at a low-moderate (5.6 km/h) work rate while wearing 4 different models of N95 filtering facepiece respirators for 1 hour each, 2 models of which were equipped with exhalation valves, while being monitored for physiologic variables. Results Compared with controls, respirator use was associated with mean 1 hour increases in heart rate (range, 5.7-10.6 beats per minute, P < .001), respiratory rate (range, 1.4-2.4 breaths per minute, P < .05), and transcutaneous carbon dioxide (range, 1.7-3.0 mm Hg, P < .001). No significant differences in oxygen saturation between controls and respirators were noted ( P > .05). Conclusion The pulmonary and heart rate responses to wearing a filtering facepiece respirator for 1 hour at a low-moderate work rate are relatively small and should generally be well tolerated by healthy persons.
Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of ...incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR.
We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%+/-18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8-2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio HR 11.4, 95% confidence interval CI 2.5-51.1) and cardiac mortality (HR 17.4, 95% CI 2.2-137.4).
In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF.
Clinicaltrials.gov NCT00493168.
Poison ivy, poison oak, and poison sumac are the most common causes of clinically diagnosed allergic contact dermatitis in North America. Approximately 50% to 75% of the US adult population is ...clinically sensitive to poison ivy, oak, and sumac. We reviewed the botany and history of these plants; urushiol chemistry and pathophysiology, clinical features, and the prevalence of allergic contact dermatitis caused by these plants; and current postexposure treatment and preventive methods, including ongoing investigations in the development of a vaccine (immunotherapy). Although extensive efforts have been made to develop therapies that prevent and treat contact dermatitis to these plants, there lacks an entirely effective method, besides complete avoidance. There is a need for a better therapy to definitively prevent allergic contact dermatitis to these plants.
Numerous statistical methods have been developed for analyzing high‐dimensional data. These methods often focus on variable selection approaches but are limited for the purpose of testing with ...high‐dimensional data. They are often required to have explicit‐likelihood functions. In this article, we propose a “hybrid omnibus test” for high‐dicmensional data testing purpose with much weaker requirements. Our hybrid omnibus test is developed under a semiparametric framework where a likelihood function is no longer necessary. Our test is a version of a frequentist‐Bayesian hybrid score‐type test for a generalized partially linear single‐index model, which has a link function being a function of a set of variables through a generalized partially linear single index. We propose an efficient score based on estimating equations, define local tests, and then construct our hybrid omnibus test using local tests. We compare our approach with an empirical‐likelihood ratio test and Bayesian inference based on Bayes factors, using simulation studies. Our simulation results suggest that our approach outperforms the others, in terms of type I error, power, and computational cost in both the low‐ and high‐dimensional cases. The advantage of our approach is demonstrated by applying it to genetic pathway data for type II diabetes mellitus.
Objectives This study sought to compare contrast-enhanced anatomic imaging and contrast-enhanced tissue characterization (delayed-enhancement cardiac magnetic resonance DE-CMR) for left ventricular ...(LV) thrombus detection. Background Contrast echocardiography (echo) detects LV thrombus based on anatomic appearance, whereas DE-CMR imaging detects thrombus based on tissue characteristics. Although DE-CMR has been validated as an accurate technique for thrombus, its utility compared with contrast echo is unknown. Methods Multimodality imaging was performed in 121 patients at high risk for thrombus due to myocardial infarction or heart failure. Imaging included 3 anatomic imaging techniques for thrombus detection (contrast echo, noncontrast echo, cine-CMR) and a reference of DE-CMR tissue characterization. LV structural parameters were quantified to identify markers for thrombus and predictors of additive utility of contrast-enhanced thrombus imaging. Results Twenty-four patients had thrombus by DE-CMR. Patients with thrombus had larger infarcts (by DE-CMR), more aneurysms, and lower LV ejection fraction (by CMR and echo) than those without thrombus. Contrast echo nearly doubled sensitivity (61% vs. 33%, p < 0.05) and yielded improved accuracy (92% vs. 82%, p < 0.01) versus noncontrast echo. Patients who derived incremental diagnostic utility from DE-CMR had lower LV ejection fraction versus those in whom noncontrast echo alone accurately assessed thrombus (35 ± 9% vs. 42 ± 14%, p < 0.01), with a similar trend for patients who derived incremental benefit from contrast echo (p = 0.08). Contrast echo and cine-CMR closely agreed on the diagnosis of thrombus (κ = 0.79, p < 0.001). Thrombus prevalence was lower by contrast echo than DE-CMR (p < 0.05). Thrombus detected by DE-CMR but not by contrast echo was more likely to be mural in shape or, when apical, small in volume (p < 0.05). Conclusions Echo contrast in high-risk patients markedly improves detection of LV thrombus, but does not detect a substantial number of thrombi identified by DE-CMR tissue characterization. Thrombi detected by DE-CMR but not by contrast echo are typically mural in shape or small in volume.
Patients with non–ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have ...obstructive coronary artery disease.
This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA.
This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively.
The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% p = 0.001, 66% p < 0.001, and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 95% confidence interval: 0.37 to 1.61; CTA vs. routine, 0.66 95% confidence interval: 0.31 to 1.42; and CMR vs. CTA, 1.19 95% confidence interval: 0.53 to 2.66). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001).
A novel strategy of implementing CMR or CTA first in the diagnostic process in non–ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.
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Given the emerging recognition of left atrial structure and function as an important marker of disease in heart failure with preserved ejection fraction (HF-pEF), we investigated the association ...between left atrial volume and function with markers of disease severity and cardiac structure in HF-pEF. We studied 100 patients enrolled in the PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial who underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise testing, and blood collection before randomization. Maximal left atrial volume index (LAVi; N = 100), left atrial emptying fraction (LAEF; N = 99; including passive and active components (LAEFP, LAEFA; N = 80, 79, respectively) were quantified by CMR. After adjustment for multiple testing, maximal LAVi was only associated with age (ρ = 0.39), transmitral filling patterns (medial E/e' ρ = 0.43), and N-terminal pro-BNP (NT-proBNP; ρ = 0.65; all p<0.05). Lower LAEF was associated with older age, higher transmitral E/A ratio and higher NT-proBNP. Peak VO2 and VE/VCO2 slope were not associated with left atrial structure or function. After adjustment for age, sex, transmitral E/A ratio, CMR LV mass, LV ejection fraction, and creatinine clearance, NT-proBNP remained associated with maximal LAVi (β = 0.028, p = 0.0007) and total LAEF (β = -0.033, p = 0.001). Passive and active LAEF were most strongly associated with age and NT-proBNP, but not gas exchange or other markers of ventricular structure or filling properties. Left atrial volume and emptying function are associated most strongly with NT-proBNP and diastolic filling properties, but not significantly with gas exchange, in HFpEF. Further research to explore the relevance of left atrial structure and function in HF-pEF is warranted.
The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased ...after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.
Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for ...infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT.
We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining.
In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (>75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (<50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT.
SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.
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