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Supplemental Material for Refining the upper limit of normal for the ascending aorta: In search of optimal criteria a large database study of normal individuals by Ji A Yoon, Mirza M Ahmad, Muhammad N Syed, Mirza N Ahmad, Sharmeen F Hussaini, Mustafa N Muhammad, Syed Haris A Pir, Bijoy K Khandheria, AJ Tajik and Khawaja A Ammar in Vascular

Patent foramen ovale (PFO) is present in about one-quarter of the population and should be considered an anatomical variant rather than a malformation. The association of PFO with cryptogenic stroke, migraine, peripheral embolism and other pathologies is still controversial. The evaluation of anatomical complexity, and particularly the long-tunnel morphology, is crucial for the assessment of the risk profile and for a targeted therapeutic management. Long-tunnel PFOs seem to be more prone to clot formation and complications related to percutaneous closure procedures. Echocardiography is the most useful method to investigate anatomical complexity, confirm and reinforce the indication to treatment, select the appropriate device and guide the PFO closure towards a successful procedure.

Additional file 1: Table S1. Stepwise analyses, including the C-statistics at each step. Table S2. Hazard ratios of continuous variables for cardiac events (cardiac death and appropriate ICD shocks) within 5 years of follow-up at multivariate analysis in patients with previous MI. Table S3. Hazard ratios of dichotomic variables for cardiac events (cardiac death and appropriate ICD shocks) within 5 years of follow-up at multivariate analysis in patients with previous MI. Table S4. Risk score data distribution (range: 0���6) by 4 steps to risk score category with adequate sample size.

In recent years, the role of left ventricular ejection fraction (EF) as the gold standard parameter for the evaluation of systolic function has been questioned, and many efforts have been concentrated in the clinical validation of new noninvasive tools for the study of myocardial contractility. Improvement in the accuracy of speckle-tracking echocardiography has resulted in a large amount of research showing the ability of two-dimensional strain to overcome EF limitations in the majority of primary and secondary heart diseases. Currently, global longitudinal strain (GLS) is considered the most accurate and sensitive parameter for the assessment of early left ventricular dysfunction. This review summarizes the advantages that this measurement can provide in several clinical settings. Moreover, the important cautions that should be considered in making the choice to use GLS also are addressed. Finally, a special focus on bull’s-eye polar maps for the assessment of regional changes of longitudinal function and the usefulness of these maps in the differential diagnosis of several diseases is provided.

Postmyocardial infarction ventricular septal defect is an increasingly rare mechanical complication of acute myocardial infarction. We present a case of acute myocardial infarction from right coronary artery occlusion that developed hypotension and systolic murmur 12 hours after successful percutaneous coronary intervention. Although preoperative imaging suggested a large ventricular septal defect and a pseudoaneurysm, intraoperative findings concluded a serpiginous dissection of the ventricular septum. The imaging technicalities are discussed.

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies.

OBJECTIVESThis study was performed to determine the accuracy and outcome implications of mitral regurgitant lesions assessed by echocardiography.BACKGROUNDIn patients with mitral regurgitation (MR), valve repair is a major incentive to early surgery and is decided on the basis of the anatomic mitral lesions. These lesions can be observed easily with transesophageal echocardiography (TEE), but the accuracy and implications for outcome and clinical decision-making of these observations are unknown.METHODSIn 248 consecutive patients operated on for MR, the anatomic lesions diagnosed with TEE were compared with those observed by the surgeon and those seen on 216 transthoracic echocardiographic (TTE) studies, and their relationship to postoperative outcome was determined.RESULTSCompared with surgical diagnosis, the accuracy of TEE was high: 99% for cause and mechanism, presence of vegetations and prolapsed or flail segment, and 88% for ruptured chordae. Diagnostic accuracy was higher for TEE than TTE for all end points (p < 0.001), but the difference was of low magnitude (

OBJECTIVESThe aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population.BACKGROUNDClinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process.METHODSThree hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined.RESULTSAge, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m2; 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively.CONCLUSIONSAtherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

The myofiber geometry of the left ventricle (LV) changes gradually from a right-handed helix in the subendocardium to a left-handed helix in the subepicardium. In this review, we associate the LV myofiber architecture with emerging concepts of the electromechanical sequence in a beating heart. We discuss: 1) the morphogenesis and anatomical arrangement of muscle fibers in the adult LV; 2) the sequence of depolarization and repolarization; 3) the physiological inhomogeneity of transmural myocardial mechanics and the apex-to-base sequence of longitudinal and circumferential deformation; 4) the sequence of LV rotation; and 5) the link between LV deformation and the intracavitary flow direction observed during each phase of the cardiac cycle. Integrating the LV structure with electrical activation and motion sequences observed in vivo provides an understanding about the spatiotemporal sequence of regional myocardial performance that is essential for noninvasive cardiac imaging.

It has now been a quarter of a century since the first description by Kitabatake and his associates of the use of echo-Doppler to characterize the transmitral flow velocity curves in various disease states. A decade ago we described the role of echocardiography in the “Evaluation of Diastolic Filling of Left Ventricle in Health and Disease: Doppler Echocardiography Is the Clinician’s Rosetta Stone.” Over the ensuing decade, advances in echo-Doppler have helped to further decipher the morphologic and physiological expression of cardiovascular disease and unlock additional mysteries of diastology. The purpose of this review is to highlight the developments in echo-Doppler and refinements in our knowledge that have occurred over the past decade that enhance our understanding of diastology.

ObjectivesWe sought to determine the association between patent foramen ovale (PFO), atrial septal aneurysm (ASA), and stroke prospectively in a unselected population sample.BackgroundThe disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity.MethodsThe use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County (Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study.ResultsA PFO was identified in 140 (24.3%) subjects and ASA in 11 (1.9%) subjects. Of the 140 subjects with PFO, 6 (4.3%) had an ASA; of the 437 subjects without PFO, 5 had an ASA (1.1%, two-sided Fisher exact test, p = 0.028). During a median follow-up of 5.1 years, cerebrovascular events (cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke (hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p = 0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA (hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p = 0.074).ConclusionsThese prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.

ObjectivesWe sought to clarify the role of isovolumic intervals during a cardiac cycle by in vivo visualization of left ventricular (LV) intracavitary flow dynamics.BackgroundAsynchronous LV deformation during isovolumic contraction (IVC) and isovolumic relaxation (IVR) might represent a transient feature of myocardial wall mechanics that reverses the direction of blood flow.MethodsIn 10 beating porcine hearts, the changes in LV intracavitary flow were recorded at baseline and after LV epicardial and right atrial pacing with high-resolution Doppler and contrast echocardiography. Two-dimensional vector flow fields were generated offline from B-mode contrast images with particle imaging velocimetry.ResultsDuring IVC, flow from the LV apex accelerated toward the base, whereas blood from the base was redirected toward the outflow through formation of an anterior vortex. Conversely, during IVR, flow was initially directed toward the apex and then briefly reversed toward the base. Epicardial pacing from the LV base altered the stages of flow redirection during the pre-ejection period and delayed mitral valve closure (28 ± 14 ms vs. 61 ± 13 ms, p < 0.001) and aortic valve opening (77 ± 18 ms vs. 111 ± 18 ms, p = 0.004).ConclusionsIsovolumic intervals are not periods of hemodynamic stasis but, rather, phases with dynamic changes in intracavitary flow. Experimentally induced aberrant epicardial electrical activation alters stages of flow redirection and prolongs the pre-ejection period. Normal electromechanical activation through the His-Purkinje system in mammalian hearts maintains an inherent synchrony with the sequence of intracavitary flow redirection.

ObjectivesThe objective of this study was to examine the relationship between Chlamydia pneumoniaeseropositivity and aortic atherosclerotic plaques in the general population.BackgroundSeroepidemiologic studies suggest that C pneumoniaeinfection plays a role in the pathogenesis of atherosclerosis.MethodsTransesophageal echocardiography was performed in 385 subjects (median age 66 years, range 51 to 101 years; 53% men), a sample of the Olmsted County (Minnesota) population. The association between C pneumoniaeimmunoglobulin (Ig) G antibody titers and aortic atherosclerotic plaques was examined.ResultsChlamydia pneumoniaeIgG antibodies (titers ≥1:16) were detected in 287 subjects (74.5%): low titers (1:16 to 1:32) in 58 (15.1%), intermediate titers (1:64 to 1:128) in 144 (37.4%), and high titers (≥1:256) in 85 subjects (22.1%). Antibody titers were not associated with the presence of aortic plaques after adjustment for age, gender, and smoking status (p = 0.64). Compared with titers

ObjectivesThe aim of this study was to explore the temporal evolution of left ventricular (LV) mechanics in relation to clinical variables and genetic expression profiles implicated in cardiac allograft function.BackgroundConsiderable uncertainty exists regarding the range and determinants of variability in LV systolic performance in transplanted hearts (TXH).MethodsFifty-one patients (mean age 53 ± 12 years; 37 men) underwent serial assessment of echocardiograms, cardiac catheterization, gene expression profiles, and endomyocardial biopsy data within 2 weeks and at 3, 6, 12, and 24 months after transplantation. Two-dimensional speckle-tracking data were compared between patients with TXH and 37 controls (including 12 post–coronary artery bypass patients). Post-transplantation mortality and hospitalizations were recorded with a median follow-up period of 944 days.ResultsGlobal longitudinal strain (LS) and radial strain remained attenuated in patients with TXH at all time points (p < 0.001 and p = 0.005), independent of clinical rejection episodes. Failure to improve global LS at 3 months (≥1 SD) was associated with higher incidence of death and cardiac events (hazard ratio: 5.92; 95% confidence interval: 1.96 to 17.91; p = 0.049). Multivariate analysis revealed gene expression score as the only independent predictor of global LS (R2 = 0.53, p = 0.005), with SEMA7A gene expression having the highest correlation with global LS (r = −0.84, p < 0.001).ConclusionsSpeckle tracking–derived LV strains are helpful in estimating the burden of LV dysfunction in patients with TXH that evolves independent of biopsy-detected cellular rejection. Failure to improve global LS at 3 months after transplantation is associated with a higher incidence of death and cardiac events. Serial changes in LV mechanics correlate with peripheral blood gene expression profiles and may affect the clinical assessment of long-term prognosis in patients with TXH.

ObjectivesThe goal of this research was to study the association between heart rate (HR) response to exercise and the risk of death and myocardial infarction (MI) after adjustment for left ventricular (LV) function and myocardial ischemia.BackgroundChronotropic incompetence during exercise testing is associated with increased mortality. It is unknown whether LV dysfunction or ischemia accounts for this.MethodsWe studied 3,221 patients (age 59 ± 12 years; 1,701 men) who underwent treadmill exercise echocardiography. We considered two markers of chronotropic incompetence: 1) failure to achieve 85% of the maximal predicted HR, and 2) low (

Left ventricular (LV) twist or torsion represents the mean longitudinal gradient of the net difference in clockwise and counterclockwise rotation of the LV apex and base, as viewed from LV apex. Twist during ejection predominantly deforms the subendocardial fiber matrix, resulting in storage of potential energy. Subsequent recoil of twist deformation is associated with the release of restoring forces, which contributes to LV diastolic relaxation and early diastolic filling. Noninvasive techniques such as magnetic resonance imaging and echocardiography are useful for understanding LV twist dynamics in clinical settings, and data regarding their relative merits and pitfalls are rapidly accumulating. This review is a focused update on the current and evolving applications of LV twist mechanics in clinical cardiology. First, the theoretical framework for understanding the physiological sequence of LV twist during a cardiac cycle is presented. Second, variations in LV twist encountered in different experimental and clinical situations are discussed. Finally, the review presents an algorithm for routine application of LV twist in clinical differentiation of patterns of LV dysfunction encountered in day-to-day practice.

The patent foramen ovale (PFO) is a normal interatrial communication during fetal life that persists after birth in approximately 1 of every 4 adults. PFO is a potential route for embolic transit from the systemic venous circulation to the brain. Though there is compelling circumstantial evidence implicating PFO, the precise role of PFO in the pathogenesis of cryptogenic stroke is not yet established. Several randomized trials of transcatheter PFO closure versus medical management are ongoing. Results of these trials may improve our ability to select the best treatment for individual patients. Further well-designed studies are necessary to address several unresolved issues related to PFO stroke and PFO migraine pathophysiology, and to identify the patients who would most likely benefit from PFO closure. The purpose of this review is to summarize contemporary understanding, discuss current treatments, and explore some of the knowledge gaps pertaining to the clinical significance of PFO.

ObjectivesThis study was designed to test the feasibility of high-resolution phased-array intracardiac imaging.BackgroundIntracardiac echocardiographic imaging of the heart during interventional electrophysiologic (EP) procedures has been limited by inadequate ultrasound penetration and absence of Doppler hemodynamic and flow information produced by rotating mechanical ultrasound elements.MethodsA 10F (3.2 mm) phased-array, variable 5.5 to 10 MHz frequency imaging catheter with a four-way deflectable tip was applied in 24 patients undergoing EP studies. Sixteen prespecified cardiac targets were imaged from a right heart venue.ResultsFifteen patients had no underlying organic heart disease; nine had ischemic, cardiomyopathic, valvular or congenital heart disorders. Longitudinal and short-axis imaging readily disclosed each cardiac valve, support structures and chamber, as well as the pericardium, right and left atrial appendages, the junction of the right atrium and superior vena cava, crista terminalis, tricuspid valve isthmus, coronary sinus orifice, membranous fossa ovalis and pulmonary veins. The average target depth was 8.8 ± 1.5 cm (range 0.5 to 15 cm), with adequate penetration at a 7.5 MHz imaging frequency. Color flow and Doppler utilities clearly characterized transaortic and pulmonic valve and pulmonary vein blood flow, including during low output states.ConclusionsThese first human studies with this technology demonstrate the methods, feasibility and utility of intracardiac phased-array vector and Doppler imaging for long-axis, apex-to-base global cardiac imaging. High resolution of endocardial structures and catheters suggests additional utility for visualizing interventional procedures from the right heart.

In recent years, the role of left ventricular ejection fraction (EF) as the gold standard parameter for the evaluation of systolic function has been questioned, and many efforts have been concentrated in the clinical validation of new noninvasive tools for the study of myocardial contractility. Improvement in the accuracy of speckle-tracking echocardiography has resulted in a large amount of research showing the ability of two-dimensional strain to overcome EF limitations in the majority of primary and secondary heart diseases. Currently, global longitudinal strain (GLS) is considered the most accurate and sensitive parameter for the assessment of early left ventricular dysfunction. This review summarizes the advantages that this measurement can provide in several clinical settings. Moreover, the important cautions that should be considered in making the choice to use GLS also are addressed. Finally, a special focus on bull’s-eye polar maps for the assessment of regional changes of longitudinal function and the usefulness of these maps in the differential diagnosis of several diseases is provided.