Original Research Put Into Perspective for the Practicing Clinician
- Transmural Differences in Myocardial Contraction in Long-QT Syndrome : Mechanical Consequences of Ion Channel Dysfunction
- Noninvasive Characterization of Epicardial Activation in Humans With Diverse Atrial Fibrillation Patterns
- Extensive Primary Repair of the Thoracic Aorta in Acute Type A Aortic Dissection by Means of Ascending Aorta Replacement Combined With Open Placement of Triple-Branched Stent Graft : Early Results
- Hemodynamic Correlates of Blood Pressure Across the Adult Age Spectrum : Noninvasive Evaluation in the Framingham Heart Study
- Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure : Relation to Disease Severity and Prognosis in the Valsartan Heart Failure Trial
- CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
- Right Ventricular Ischemic Injury in Patients With Acute ST-Segment Elevation Myocardial Infarction : Characterization With Cardiovascular Magnetic Resonance
- Podoplanin-Expressing Cells Derived From Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization
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Transmural Differences in Myocardial Contraction in Long-QT Syndrome : Mechanical Consequences of Ion Channel Dysfunction
The long-QT syndrome (LQTS) is due to inherited cardiac ion channel defects and predisposes to life-threatening ventricular arrhythmias and sudden cardiac death. Current risk stratification of ventricular arrhythmias is based on a history of syncope or documented arrhythmia, heart rate–corrected QT interval on the ECG (QTc), gender, and genotype. However, QTc is insufficient as a significant predictor of arrhythmic outcome. LQTS has traditionally been regarded as a purely electric disease. Strain by echocardiography can accurately quantify regional myocardial timing and function. Echocardiography was performed in 101 genotyped LQTS patients (53 asymptomatic and 48 with a history of cardiac arrhythmias) and 35 healthy control subjects. Left ventricular contraction pattern by strain was assessed as time from the ECG Q wave to maximum myocardial shortening in 16 LV segments. Strain was assessed along the longitudinal axis, predominantly representing subendocardial fibers, and along the circumferential axis, representing midmyocardial fibers. This study shows that LQTS patients have abnormal LV contraction patterns. Contraction duration was longer and more heterogeneous in symptomatic LQTS mutation carriers compared with asymptomatic patients. In addition, contraction duration was longer in the subendocardium than in the midmyocardium, indicating a pronounced transmural mechanical dispersion that was not present in asymptomatic and healthy individuals. Our findings suggest that echocardiography might be a complementary tool to QTc and may provide added value in risk stratification of LQTS mutation carriers. See p 1355.
Noninvasive Characterization of Epicardial Activation in Humans With Diverse Atrial Fibrillation Patterns
Atrial fibrillation (AF) is the most common cardiac arrhythmia, accountable for frequent hospitalizations and increased risks of stroke, heart failure, and mortality. Various mechanisms of AF have been demonstrated in experimental models. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution in a closed chest. This article presents simultaneous biatrial epicardial activation sequences during AF for a range of AF phenotypes in 26 patients, obtained noninvasively with the use of ECG imaging. From a diagnostic standpoint, ECG imaging offers a way to describe a particular patient's AF with the use of continuous noninvasive mapping of atrial electric activity. By imaging atrial electrophysiology, it offers an advantage over the current classification of AF, which relies on historical descriptors of duration and method of AF termination (paroxysmal, persistent, or permanent). Better identification of specific phenotypes ultimately may translate into tailored, patient-specific treatment plans that maximize benefit while minimizing risk. Examples include predicting and monitoring response to antiarrhythmic drug therapy or developing a customized catheter ablation lesion set. In this article, locations critical to maintenance of AF were identified in 3 patients during catheter ablation procedures and correlated with the ECG imaging findings. Ablation near these sites restored sinus rhythm. Prospective studies in homogeneous phenotypic subgroups would be needed to better define the role of ECG imaging in the treatment of patients with AF. See p 1364.
Extensive Primary Repair of the Thoracic Aorta in Acute Type A Aortic Dissection by Means of Ascending Aorta Replacement Combined With Open Placement of Triple-Branched Stent Graft : Early Results
In surgical extensive primary repair of the thoracic aorta for acute type A aortic dissection, careful manipulation of the arch and elaborate anastomoses to the distal arch and 3 arch vessels are time-consuming and could induce phrenic and recurrent laryngeal nerve injury. Our results suggest that extensive primary repair of the thoracic aorta for acute type A aortic dissection can be performed simply by both open placement of the triple-branched stent graft into the proximal descending aorta, arch, and 3 arch vessels and graft replacement of the ascending aorta, which can reduce the risk and technical difficulties of extensive thoracic aorta repair to close to those of the conventional ascending graft replacement with open distal anastomosis. Therefore, with open placement of triple-branched stent graft, extensive primary repair of the thoracic aorta may become easier and safer for acute type A aortic dissection. Careful long-term follow-up and further extensive clinical use are necessary to completely evaluate the efficacy of this new technique. See p 1373.
Hemodynamic Correlates of Blood Pressure Across the Adult Age Spectrum : Noninvasive Evaluation in the Framingham Heart Study
Blood pressure increases substantially and nonlinearly with age across the adult lifespan. Mean arterial pressure and pulse wave velocity increase and pulse pressure decreases before 50 years of age, whereas systolic and pulse pressures and pulse wave velocity increase markedly thereafter, at a time when the prevalence of hypertension and cardiovascular disease is high. The pathogenesis of nonlinear age trajectories of blood pressure components has been debated vigorously in recent years, with some suggesting that elevated pulse wave velocity and premature wave reflection account for the increase in pulse pressure. We found that forward wave amplitude is the predominant hemodynamic correlate of pulse pressure across the adult age spectrum and accounts for an overwhelming majority of the accelerated increase in pulse pressure after 50 years of age. Differences in relative wave reflection contribute modestly to variability in pulse pressure, whereas reflected wave timing plays a minimal role. Differing age relations of pulse wave velocity and pulse pressure, which were divergent before 50 years of age and concordant thereafter, suggest that alterations in aortic diameter may modulate changes in pulse pressure in the face of changes in wall stiffness and pulse wave velocity. Additional studies are needed to define the mechanisms that contribute to aortic wall stiffening with advancing age and risk factor exposure and to clarify the role of aortic diameter. A fuller understanding of the pathogenesis of increased pulse pressure and systolic hypertension is needed and will facilitate development of more rational approaches to the treatment of hypertension. See p 1379.
Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure : Relation to Disease Severity and Prognosis in the Valsartan Heart Failure Trial
There is a growing interest in using biomarkers to obtain pathophysiological insight into and, possibly, to improve the management of patients with heart failure (HF). Considering that HF is a systemic disease, biomarkers reflecting cardiac and systemic abnormalities may add incremental information to cardiac-specific markers such as B-type natriuretic peptide and high-sensitivity troponin T. Growth-differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-β cytokine superfamily that is produced in the heart and vasculature in response to tissue injury and inflammation. Accumulating evidence indicates that the circulating levels of GDF-15 are associated with prognosis in patients with coronary artery disease. In the present subinvestigation from the Valsartan Heart Failure Trial (Val-HeFT), 85% of the patients with advanced, stable, chronic HF had elevated circulating levels of GDF-15. GDF-15 levels further increased during the course of 12 months in both the placebo and valsartan arms of the trial. Increases in GDF-15 were independently associated with the risks of future mortality and first morbid event after adjustment for clinical prognostic variables, B-type natriuretic peptide, and high-sensitivity troponin T and their 12-month changes. Changes in GDF-15 over time may therefore reflect a pathophysiological process that is related to the prognosis of HF and is not completely addressed by the therapies prescribed to the patients in Val-HeFT. Continued research should focus on the potential clinical application of GDF-15 as a biomarker in HF and an improved understanding of its pathophysiology that may reveal new treatment targets in HF. See p 1387.
CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
The mechanisms involved in the immune activation observed during the progression of human chronic heart failure and dilated cardiomyopathy have not been fully elucidated. However, a number of recent studies suggest that, besides genetic susceptibility and infections, chronic immune-mediated inflammation after acute myocarditis may lead to dilated cardiomyopathy. This report investigates the role of the leukocyte activation antigen CD69 in the modulation of the inflammatory response in a mouse model of autoimmune myocarditis. Our data demonstrate that CD69, through the regulation of Th17 effector responses, limits myocardial inflammation and subsequent heart failure. It is very feasible that a similar phenomenon occurs in humans with myocarditis and subsequent dilated cardiomyopathy. These findings reveal the involvement of a novel molecular actor in the immunopathogenesis of myocarditis, which could be a potential therapeutic target. See p 1396.
Right Ventricular Ischemic Injury in Patients With Acute ST-Segment Elevation Myocardial Infarction : Characterization With Cardiovascular Magnetic Resonance
Cardiovascular magnetic resonance (CMR) is being used increasingly in myocardial infarction imaging in both acute and chronic settings. Although most studies, thus far, have focused on the left ventricle (LV), CMR has been shown to be useful in evaluating ischemic right ventricular (RV) myocardial injury as well. In the present study, a total of 242 patients with reperfused acute ST-segment myocardial infarction from 3 tertiary hospitals underwent CMR early and at 4 months after infarction. CMR included assessment of myocardial edema with the use of T2-weighted imaging, myocardial enhancement with the use of late gadolinium enhancement CMR, and biventricular function with the use of cine imaging. Ischemic RV injury was commonly present early after infarction, characterized by myocardial edema (51% of patients), late gadolinium enhancement (31% of patients) of RV free wall adjacent to jeopardized LV myocardium, and functional abnormalities. Remarkably, this pattern of RV injury was not limited to inferior LV infarcts but occurred in anterior infarcts as well. Follow-up CMR showed reversibility of acute RV dysfunction with limited permanent myocardial damage on late gadolinium enhancement imaging (10% of patients). These findings support previous clinical and animal studies showing that the RV is more resistant to ischemia than the LV and that acute postinfarction RV dysfunction is likely an expression of viable rather than irreversibly damaged myocardium. Moreover, it is important to realize that in patients with anterior LV infarction, ischemia may extend toward the adjacent RV free wall and lead to transient RV dysfunction. See p 1405.
Podoplanin-Expressing Cells Derived From Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization
In this study, we identified podoplanin-expressing lymphatic endothelial progenitor cells derived from bone marrow. Injection of these podoplanin-expressing lymphatic endothelial progenitor cells into various animal models showed the contribution of these cells to the formation of new lymphatic vessels through direct transdifferentiation and paracrine effects. This lymphatic vessel–forming capability can be used for the treatment of lymphedema or chronic unhealed wounds, which are characterized by lymphatic vascular insufficiency. Moreover, this study demonstrated an increase in the number of circulating lymphatic endothelial progenitor cells in tumor-bearing mice, suggesting that lymphatic endothelial progenitor cells are correlated with tumor-associated lymphatic vascular growth. This property can be harnessed for the development of a biomarker for monitoring tumor burden, tumor growth, and/or metastasis. See p 1413.
- © 2010 American Heart Association, Inc.
- CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
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