Circulation: Cardiovascular Imaging's Editors' Picks

Abstract

HomeCirculation: Cardiovascular ImagingVol. 5, No. 3Circulation: Cardiovascular Imaging's Editors' Picks Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessReview ArticlePDF/EPUBCirculation: Cardiovascular Imaging's Editors' PicksMost Important Articles in Clinical Translation of Novel Imaging Technologies The Editors The Editors Search for more papers by this author Originally published1 May 2012https://doi.org/10.1161/CIRCIMAGING.112.975854Circulation: Cardiovascular Imaging. 2012;5:e26–e34Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte StiffnessSummary:In aging populations, diabetes mellitus (DM) and aortic stenosis (AS) are becoming frequent comorbidities. Studies looking at the interaction between DM and AS investigated mainly the progression of sclerocalcific valvular dysfunction. In heart failure (HF), DM increases diastolic left ventricular (LV) stiffness, which adversely affects morbidity and mortality. The DM-related increase in diastolic LV stiffness was observed both in HF with a reduced ejection fraction and in HF with a normal ejection fraction. In HF with a reduced ejection fraction, DM affected myocardial stiffness through excessive fibrosis and arteriolar or capillary deposition of advanced glycation end products, whereas in HF with a normal ejection fraction, DM increased myocardial stiffness through elevation of cardiomyocyte resting tension (Fpassive). The present clinical study extended these observations on DM-related worsening of diastolic LV stiffness to symptomatic AS and confirmed a similar increase in diastolic LV stiffness in patients experiencing both AS and DM. This increase was evident from a higher LV end-diastolic pressure at a comparable LV end-diastolic volume index. Furthermore, the increase in diastolic LV stiffness resulted from all 3 previously mentioned mechanisms (ie, excessive fibrosis, intramyocardial vascular advanced glycation end product deposition, and elevated cardiomyocyte Fpassive). The latter could be attributed to hypophosphorylation of the stiff isoform of the cytoskeletal protein titin, which is largely responsible for cardiomyocyte Fpassive. The observed increase in diastolic LV stiffness in patients experiencing both AS and DM could predispose them to earlier development of HF symptoms and an earlier need for aortic valve replacement.Conclusions:Worse diastolic LV dysfunction in AS-DM predisposes to HF and results from more myocardial fibrosis, more intramyocardial vascular advanced glycation end product deposition, and higher cardiomyocyte Fpassive, which was related to hypophosphorylation of the N2B titin isoform.1Myocardial Steatosis and Biventricular Strain and Strain Rate Imaging in Patients With Type 2 Diabetes MellitusSummary:The underlying origin of diabetic heart disease is likely to be multifactorial, ranging from altered myocardial metabolism to endothelial dysfunction, microvascular disease, autonomic neuropathy, and altered myocardial structure with fibrosis. Increasing evidence is emerging on the role of lipotoxic myocardial injury from lipid oversupply. By using magnetic resonance imaging and proton magnetic resonance spectroscopy, the present study evaluated the association between myocardial triglyceride accumulation and altered biventricular myocardial function by 2D speckle tracking echocardiography in patients with type 2 diabetes. Diabetic patients with a high myocardial triglyceride content had significantly more impaired biventricular myocardial functions despite normal volumes and ejection fraction. On multivariate analyses, myocardial triglyceride content was an independent determinant of biventricular myocardial functions. Future studies assessing the effectiveness of antisteatotic therapy in patients with type 2 diabetes may include quantifications of myocardial triglyceride content by spectroscopy and assessments of myocardial functions by strain/strain rate imaging on 2D speckle tracking echocardiography.Conclusions:High myocardial triglyceride content is associated with more pronounced impairment of left and right ventricular functions in men with uncomplicated type 2 diabetes mellitus.2Association of Imaging Markers of Myocardial Fibrosis With Metabolic and Functional Disturbances in Early Diabetic CardiomyopathySummary:Myocardial dysfunction is common in apparently well subjects with type 2 diabetes mellitus. Myocardial fibrosis is increasingly recognized as a potential contributor to this process and has plausible connections with hyperglycemia and other metabolic factors. Noninvasive identification of myocardial fibrosis is challenging, because endomyocardial biopsy cannot be justified in asymptomatic subjects. Recently, cardiac magnetic resonance T1 mapping techniques have been developed to enable quantification of diffuse fibrosis. Other imaging parameters, such as backscatter and tissue Doppler imaging (tissue velocity, strain, and strain rate), are useful in identifying subclinical myocardial structural and functional abnormalities that may be related to underlying fibrosis. Myocardial collagen turnover can also be estimated noninvasively by measuring procollagen biomarker levels in peripheral blood. The authors hypothesized that a relationship could be established between these noninvasive markers of myocardial fibrosis and metabolic control in type 2 diabetes mellitus. This would support fibrosis as an underlying mechanism for myocardial dysfunction and suggest that metabolic derangement is a predisposing factor. In a multimodality study of 67 subjects with type 2 diabetes mellitus, T1 values on cardiac magnetic resonance were compared with echocardiographic parameters of subclinical diabetic heart disease, procollagen biomarker levels, and metabolic control. The association between diastolic dysfunction and metabolic derangement was confirmed. The authors also found a relationship between myocardial diastolic dysfunction, postcontrast T1 values, and procollagen biomarkers that supports that diffuse myocardial fibrosis may be an underlying mechanism of early nonischemic diabetic cardiomyopathy.Conclusions:The association between myocardial diastolic dysfunction, postcontrast T1 values, and metabolic disturbance supports that diffuse myocardial fibrosis is an underlying contributor to early diabetic cardiomyopathy.3Editor's CommentDiabetes mellitus increases the risk of heart failure after myocardial infarction and confers a worse prognosis once heart failure symptoms develop in patients with preserved or reduced left ventricular (LV) ejection fraction (EF). These 3 studies provide complementary information regarding unique histomorphometric, structural, and metabolic abnormalities that are present in the diabetic heart. The studies by Falcão-Pires1 and Jellis3 and colleagues confirm increased LV end-diastolic pressure and diastolic dysfunction in diabetics despite similar LV volumes and LVEF. Falcão-Pires showed that the altered hemodynamics in diabetic patients are associated with increased collagen volume, reflecting interstitial fibrosis, and more advanced glycation end product deposition in arterioles, venules, and capillaries. Jellis et al extend this observation in vivo by demonstrating that imaging markers of diffuse fibrosis by echocardiography and magnetic resonance imaging are more prevalent in diabetes, and that they have a close association with abnormalities in diastolic function. Moreover, Falcão-Pires showed that, beyond fibrosis, cardiomyocyte distensibility is lower in diabetics despite similar degrees of hypertrophy, a finding that is linked to reduced phosphorylation of the stiff Titin isoform. The study by Ng et al2 extends these observations by demonstrating that diabetic patients with high myocardial triglyceride content, as assessed by magnetic resonance spectroscopy, show greater impairment of LV and right ventricular (RV) myocardial strain and strain rate, as defined by speckle-tracking echocardiography. In this study, the myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate.Transmural Differences in Myocardial Contraction in Long-QT Syndrome: Mechanical Consequences of Ion Channel DysfunctionSummary:The long-QT syndrome (LQTS) is the result of 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), sex, and genotype. However, QTc is insufficient as a significant predictor of arrhythmic outcome. The 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 patients with LQTS (53 asymptomatic and 48 with a history of cardiac arrhythmias) and 35 healthy control subjects. The left ventricular contraction pattern by strain was assessed as time from the ECG Q wave to maximum myocardial shortening in 16 left ventricular (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 patients with LQTS 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. The authors' findings suggest that echocardiography might be a complementary tool to QTc and may provide added value in risk stratification of LQTS mutation carriers.Conclusions:The contraction duration in symptomatic LQTS mutation carriers was longer in the subendocardium than in the midmyocardium, indicating transmural mechanical dispersion, which was not present in asymptomatic and healthy individuals.Editor's CommentAdvances in imaging allow more detailed assessments of cardiac structure and function, and there are emerging data that this additional phenotypic characterization may improve diagnosis and risk prediction. This study demonstrates that patients with LQTS have abnormally prolonged contraction in the LV long axis, as assessed by strain echocardiography, reflecting predominantly subendocardial dysfunction. Transmural differences in contraction durations were rather diffuse, which is not surprising given the fact that patients with LQTS have demonstrated abnormalities in calcium channels. Interestingly, the observation that increased dispersion of contraction duration was associated with increased risk for cardiac arrhythmias opens the possibility of improved risk stratification in this patient cohort.4Cardiac Magnetic Resonance Imaging Pericardial Late Gadolinium Enhancement and Elevated Inflammatory Markers Can Predict the Reversibility of Constrictive Pericarditis After Anti-Inflammatory Medical Therapy: A Pilot StudySummary:Constrictive pericarditis (CP) is a disabling disease and usually requires pericardiectomy to relieve heart failure symptoms. Reversible cases of CP after anti-inflammatory therapy have been described, but there is no known method to predict the reversibility. The authors report their pilot study to assess whether cardiac magnetic resonance imaging (CMR) pericardial late gadolinium enhancement (LGE) can predict the reversibility of CP after a course of anti-inflammatory therapy. Twenty-nine patients received anti-inflammatory medications after CMR. Fourteen patients had resolution of CP, whereas 15 had persistent constrictive physiological features. Baseline LGE pericardial thickness was greater in the reversible CP group than in the persistent CP group. Qualitatively rated severity of pericardial LGE was moderate or severe in 93% of the reversible CP group versus 33% of the persistent CP group. A CMR LGE pericardial thickness ≥3 mm had 86% sensitivity and 80% specificity to predict reversibility. The reversible CP group also had a higher baseline C-reactive protein and erythrocyte sedimentation rate level than the persistent CP group. Anti-inflammatory therapy was associated with a reduction in pericardial LGE, C-reactive protein, and erythrocyte sedimentation rate in the reversible CP group but not in the persistent CP group. The findings in this pilot observation suggest that reversible CP is associated with pericardial and systemic inflammation. Furthermore, anti-inflammatory therapy is associated with a reduction of pericardial and systemic inflammation, as well as pericardial thickness, on CMR LGE imaging, with resolution of constrictive physiological features and symptoms. Anti-inflammatory therapy should be considered in patients with CP who have these features before pericardiectomy.Conclusions:Reversible CP was associated with pericardial and systemic inflammation. Anti-inflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiological features and symptoms. Further studies in more patients are needed.Editor's CommentConstrictive pericarditis is characterized anatomically by increased pericardial fibrosis, which is frequently associated with calcification. Although the contribution of inflammation to this process has been recognized, the quantification of its contribution has been more challenging. This is important because it is potentially reversible with anti-inflammatory therapy. This study offers preliminary evidence that the thickness of pericardial LGE by magnetic resonance imaging (reflecting both fibrosis and expansion of the extracellular space, presumably caused by edema) may serve as a useful surrogate marker of inflammation, especially when associated with evidence of circulating biomarker evidence of inflammation. Future studies will have to confirm the utility of LGE to identify potentially reversible constrictive pericarditis, and validate quantitative thresholds that can prospectively differentiate the relative contribution of fibrosis and inflammation.5Quantification of Diffuse Myocardial Fibrosis and Its Association With Myocardial Dysfunction in Congenital Heart DiseaseSummary:There is growing recognition that progressive myocardial dysfunction in patients with congenital heart disease contributes substantially to clinical heart failure, arrhythmia, and mortality. Magnetic resonance imaging (MRI) with late gadolinium enhancement has been used to demonstrate areas of replacement fibrosis in several subgroups of congenital heart disease, confirming that myocardial fibrosis is a likely final common pathway in these patients. However, late enhancement identifies dense replacement fibrosis and is not as amenable to detecting smaller amounts of diffuse, microscopic fibrosis. To quantify myocardial fibrosis, the authors used a modified Look-Locker sequence to quantify a “fibrosis index” based on T1 times for a single short-axis plane of the systemic ventricle before and after administration of gadolinium-based contrast. In 50 patients with congenital heart disease, the fibrosis index was significantly elevated in patients compared with healthy controls and especially elevated in patients with a systemic right ventricle and those with cyanosis. The fibrosis index correlated with end-diastolic volume index and ventricular ejection fraction but not with age. Values for patients with congenital heart disease were largely similar to those for patients with cardiomyopathy. The findings lay the groundwork for further investigation on the pathophysiological features and treatment of heart failure, specifically in congenital heart disease.Conclusions:Patients with adult congenital heart disease have evidence of diffuse, extracellular matrix remodeling, similar to patients with acquired heart failure. The fibrosis index may facilitate studies on the mechanisms and treatment of myocardial fibrosis and heart failure in these patients.Editor's CommentMany individuals with congenital heart disease undergo surgery early in life and live productive lives into adulthood. However, over time, the systemic ventricle often fails and much work is being done to understand this more fully to intervene at a time to change the outcome. Myocardial fibrosis is a frequent final common pathway for many myocardial insults; in this study, Broberg et al quantitate the degree of fibrosis using a newly derived fibrosis index. They demonstrate the relationship of the index to ventricular volume and ejection fraction but do not evaluate diastolic function. The importance of the observation is not so much that fibrosis occurs but that quantitation using cardiac MRI in patients with congenital heart disease is feasible and that serial evaluation, coupled with assessment of more subtle functional abnormalities, may facilitate an earlier therapeutic intervention.6Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Patients With Endomyocardial FibrosisSummary:The authors evaluated the role of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) for the diagnosis of endomyocardial fibrosis (EMF) using surgical specimens as the standard method. The LGE-CMR confirmed the diagnoses of EMF patients on the basis of areas of LGE that were confined to the endocardium as continuous stria from the inflow tract to the apex. The histopathological characteristics of fibrous tissue in 14 patients showed typical features of EMF. This study provides evidence that LGE-CMR is a reliable diagnostic tool to confirm EMF.Conclusions:The study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition.Editor's CommentEndomyocardial fibrosis is the most common restrictive cardiomyopathy worldwide, and echocardiography is widely used to characterize the disease and prognosis. In late-stage disease, the imaging features are fairly characteristic, but there is overlap with other diseases. This descriptive study reports on the distribution and pattern of subendocardial changes using LGE cardiac magnetic resonance imaging and reinforces the relatively unique pattern of endocardial distribution. This study was not designed to assess the utility of the imaging findings in making the diagnosis of EMF but does serve as a foundation for future studies and potentially as a method to assess innovative treatment and timing of surgery.7Prediction of Cardiac Resynchronization Therapy Response: Value of Calibrated Integrated Backscatter ImagingSummary:According to current guidelines, candidates for cardiac resynchronization therapy (CRT) are patients in New York Heart Association functional class III to IV heart failure with left ventricular (LV) ejection fraction ≤35% and QRS duration ≥120 ms. However, by applying these selection criteria, more than one third of the patients do not show clinical response nor LV reverse remodeling. Among several factors that determine a favorable response to CRT, the amount of LV fibrosis as assessed, for example, with cardiac magnetic resonance has been an important issue. The current study demonstrates that myocardial ultrasonographic reflectivity is an important determinant of CRT response in the overall heart failure population, together with the presence of LV mechanical dyssynchrony and renal function. Moreover, in the ischemic subgroup of patients with heart failure, myocardial ultrasonographic reflectivity was the only independent determinant of LV reverse remodeling after CRT. In the nonischemic subgroup of patients with heart failure, myocardial ultrasonographic reflectivity was still an independent predictor of CRT response. Several pathophysiological issues must be addressed to optimize selection of patients with CRT. Different imaging modalities provide information about dyssynchrony, and echocardiography has provided useful, albeit controversial, data in these patients. Myocardial ultrasonographic reflectivity with calibrated integrated backscatter imaging may provide additional data to aid in the selection of candidates for CRT.Conclusions:Assessment of myocardial ultrasonographic reflectivity is important in the prediction of CRT response in ischemic and nonischemic patients.Editor's CommentThe previous 2 studies have used cardiac magnetic resonance imaging (MRI) to evaluate cardiac fibrosis, and the interest in using MRI for this seems to be growing progressively. For many years, echocardiographers have attempted to quantitate myocardial echo characteristics and reflectivity as indicators of “scarring” and presumptive fibrosis. This technique, however, has not gained widespread acceptance nor found a real clinical niche. In this study, the authors demonstrate that, in all patients and particularly in those with ischemic heart failure undergoing CRT, responders demonstrated less reflectivity using calibrated integrated backscatter. Intuitively, this is understandable, but whether this technique will aid in improving patient selection for CRT remains uncertain.8Left Atrial Strain and Strain Rate in Patients With Paroxysmal and Persistent Atrial Fibrillation: Relationship to Left Atrial Structural Remodeling Detected by Delayed-Enhancement Magnetic Resonance ImagingSummary:The underlying substrate for atrial fibrillation (AF) is fibrosis, a marker of structural remodeling. The AF leads to progressive structural and functional changes in the left atrium (LA). Delayed-enhancement (DE) magnetic resonance imaging (MRI) has detected LA fibrosis. With vector velocity imaging, using speckle tracking technology, quantification of atrial strain throughout the cardiac cycle from gray-scale images is feasible. Strain is an indicator of LA compliance or reservoir function, which is impaired in AF caused by fibrosis. Vector velocity imaging overcomes some of the limitations of Doppler-based strain measurements, such as angle dependency and influence by loading conditions. In this study, the authors demonstrated an inverse relationship between LA fibrosis by DE-MRI and LA midlateral strain and strain rate by vector velocity imaging. This relationship was more prominent in patients with persistent compared with paroxysmal AF. Lateral wall strain can be reliably imaged and may be used as a surrogate of LA wall fibrosis by DE-MRI. Interestingly, LA fibrosis and strain were not related to common causes for AF, such as patient age, hypertension, left ventricular filling pressure, or mitral regurgitation. Regardless of the underlying cause or the duration of AF, the degree of atrial fibrosis was the main determinant of severity of arrhythmia in this cohort. Noninvasive imaging of LA fibrosis may be helpful in predicting the risk of developing AF, guiding therapeutic strategies, and predicting the outcomes in patients with AF. It may allow us to identify patients earlier in their disease process, before the development of severe or irreversible abnormalities.Conclusions:The LA wall fibrosis by delayed-enhancement MRI is inversely related to LA strain and strain rate, and these are related to the AF burden. Echocardiographic assessment of LA structural and functional remodeling is quick and feasible and may be helpful in predicting outcomes in AF.Editor's CommentIt is believed that, in most patients, hemodynamic changes in the left atrium initiate structural changes in the left atrium that ultimately result in the arrhythmogenic substrate that initiates and sustains atrial fibrillation. In this study, the authors combine the cardiac MR-determined morphological and structural changes in the left atrium with sensitive functional strain measurements determined by echo using velocity vector imaging. At the extreme, when the atrium is large, the likelihood of maintaining sinus rhythm is small and there are surely steps along the continuum that will allow more appropriate decision making. The retrospective cross-sectional nature of the study limits the ability to use this information prospectively and directly to tailor treatment strategies, but this study provides an important integrated approach to refine therapeutic approaches.9Preoperative Systolic Strain Rate Predicts Postoperative Left Ventricular Dysfunction in Patients With Chronic Aortic RegurgitationSummary:In patients with chronic aortic regurgitation, preoperative and postoperative left ventricular systolic function is an important determinant of postoperative prognosis. However, the best predictor for postoperative left ventricular systolic dysfunction in patients with chronic aortic regurgitation is still a matter of debate. The aim of this study was to assess the clinical significance of preoperative systolic radial strain rate (Ssr) derived from tissue Doppler echocardiography as a predictor of postoperative left ventricular systolic dysfunction in patients with chronic aortic regurgitation. In 52 patients with chronic aortic regurgitation, the operation caused significant decreases in left ventricular dimensions and volumes and significant increase in Ssr and left ventricular ejection fraction. Multiple regression analysis demonstrated that averaged Ssr was the only independent predictor of postoperative left ventricular systolic dysfunction. By using receiver-operating characteristic curve analysis, averaged Ssr yielded the greatest area under the curve among preoperative parameters (0.80) and was identified as being a good predictor of postoperative left ventricular dysfunction, with 90.9% sensitivity and 73.2% specificity (cutoff value, 1.82/second). The results of this study suggest that the measurement of Ssr may be a useful tool for estimation of subclinical myocardial dysfunction and for optimizing surgical timing, especially in patients for whom there is debate about the need for and timing of surgery.Conclusions:Measurement of preoperative averaged Ssr is useful in predicting postoperative left ventricular (LV) systolic dysfunction and optimizing surgical timing in patients with isolated chronic aortic regurgitation.Editor's CommentThe timing of surgery in patients with aortic regurgitation remains challenging. This study describes the utility of the systolic radial strain rate in a group of patients with chronic isolated aortic regurgitation who underwent various approaches to correcting the regurgitation, including different types of prostheses and valve-sparing surgical procedures. The preoperative studies were performed relatively close to the surgical procedure, whereas the postoperative studies were acquired ≈1 year±3 months after the surgical procedure. Most patients had fairly advanced disease, based on LV volumes; in this cohort, the radial strain rate was useful in predicting recovery of systolic function, as determined by ejection fraction. The impact of loading conditions and preoperative medicines, which were not standardized, on strain rate cannot be determined from this study and, thus, the widespread applicability and utility will require further study.10Strain Echocardiography and Wall Motion Score Index Predicts Final Infarct Size in Patients With Non–ST-Segment–Elevation Myocardial InfarctionSummary:Infarct size is a strong prognostic indicator after myocardial infarction. In patients with ST-segment–elevation myocardial infarction, reperfusion therapy is effective in reducing infarct size and has improved survival. However, a proportion of patients with non–ST-segment–elevation myocardial infarction also experience substantial myocardial infarction, but these patients are rarely eligible for acute reperfusion therapy. Severe myocardial ischemia and necrosis are not always reflected in ST-segment–elevation, and these patients often do not reveal clinical signs of instability. Hence, there is a need for other modalities to identify these patients. Abundant evidence has demonstrated that myocardial ischemia causes rapid deterioration of myocardial systolic function. Echocardiography is a fast and available tool for estimation of myocardial systolic function. The left ventricular ejection fraction and wall motion score index are conventional parameters used to estimate left ventricular systolic function. Recently, strain measurement by speckle tracking has emerged as a new modality. The present study demonstrates that patients with non–ST-segment–elevation myocardial infarction with substantial myocardial infarction can be identified by echocardiographic parameters of left ventricular systolic function. The global longitudinal strain and wall motion score index both demonstrate excellent discriminating power. Echocardiography and particularly strain echocardiography may facilitate the evaluation of interventions that affect outcomes in patients with non–ST-segment–elevation myocardial infarction.Conclusions:Echocardiographic parameters of LV systolic function correlate to infarct size in patients with non–ST-segment–elevation myocardial infarction. Global longitudinal strain and wall motion score index are both excellent parameters to identify patients with substantial myocardial infarction, who may benefit from urgent reperfusion therapy.Editor's CommentThe impetus for this study is the recognition that patients with non–ST-segment–elevation myocardial infarction (NSTEMI) may have significant myocardial dysfunction and might, therefore, benefit fro