JACC: Cardiovascular Imaging

Impact of Aortic Regurgitation After Transcatheter Aortic Valve Implantation: Results From the REVIVAL Trial

2012-05-01

Objectives: Understanding the severity of aortic regurgitation (AR) after transcatheter aortic valve implantation, its impact on left ventricular (LV) structure and function, and the structural factors associated with worsening AR could lead to improvements in patient selection, implantation technique, and valve design. Background: Initial studies in patients at high risk of surgical aortic valve replacement have reported both central valvular and paravalvular AR after transcatheter aortic valve implantation. Methods: Transthoracic echocardiograms were quantified from 95 patients in the REVIVAL (TRanscatheter EndoVascular Implantation of VALves) trial. Transthoracic echocardiograms were obtained before implantation of the Edwards-Sapien valve (Edwards Lifesciences, Irvine, California) and thereafter at selected intervals. Measurements included LV internal diameters and volumes, ejection fraction, aortic valve area, and the degree of aortic regurgitation. Measures of degree of native leaflet mobility, thickness, and calcification, as well as left ventricular outflow tract, aortic annulus, and aortic root diameters were also made. Results: Eighty-four patients remained after 11 were excluded; 26 (29.8%) died over a period of 3 years. At 24 h post-implantation, 75% had some degree of AR, mostly paravalvular. By 1 year, the mean AR grade increased slightly, but not significantly (1.1 ± 0.8 to 1.3 ± 0.9), and all measures of LV structure and function improved (LV ejection fraction, 50.7 ± 16.1% to 59.4 ± 14.0%). Native aortic leaflet calcification and annulus diameter correlated significantly with the severity of AR at 1 year (p < 0.05). Conclusions: AR after transcatheter aortic valve implantation is frequent but is rarely more than mild. Although AR progresses, it is not associated with a harmful impact on LV structure and function over the first year. Native valve calcification and aortic annulus diameter influence the degree of AR at 6 months.

Direct Assessment of Normal Mechanical Mitral Valve Orifice Area by Real-Time 3D Echocardiography

2012-05-01

A reliable method for the assessment of the mitral valve (MV) area is essential for the management of patients with a prosthetic MV. In this study, we assess the feasibility of 3-dimensional (3D) echocardiography to directly measure the mechanical MV orifice area in both an in vitro study of prosthetic valve function under controlled-flow conditions as well as in a clinical imaging protocol. The 3D anatomic diastolic area (ADA) and 3D color Doppler diastolic area were compared with a manufacturer-defined geometric orifice area (GOA) and Doppler-derived effective orifice area (EOA) for normal mechanical MVs ().

Image Quality and Radiation Exposure With Prospectively ECG-Triggered Axial Scanning for Coronary CT Angiography: The Multicenter, Multivendor, Randomized PROTECTION-III Study

2012-05-01

Objectives: The purpose of this study was to evaluate image quality and radiation dose using a prospectively electrocardiogram (ECG)–triggered axial scan protocol compared with standard retrospective ECG-gated helical scanning for coronary computed tomography angiography. Background: Concerns have been raised regarding radiation exposure during coronary computed tomography angiography. Although the use of prospectively ECG-triggered axial scan protocols may effectively lower radiation dose compared with helical scanning, it is unknown whether image quality is maintained in a clinical setting. Methods: In a prospective, multicenter, multivendor trial, 400 patients with low and stable heart rates were randomized to either an axial or a helical coronary computed tomography angiography scan protocol. The primary endpoint was to demonstrate noninferiority in image quality with the axial scan protocol, which was assessed on a 4-point scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints included radiation dose and the rate of downstream testing during 30-day follow-up. Results: Image quality in patients scanned with the axial scan protocol (score 3.36 ± 0.59) was not inferior compared with helical scan protocols (3.37 ± 0.59) (p for noninferiority <0.004). Axial scanning was associated with a 69% reduction in radiation exposure (dose-length product [estimated effective dose] 252 ± 147 mGy · cm [3.5 ± 2.1 mSv] vs. 802 ± 419 mGy · cm [11.2 ± 5.9 mSv] for axial vs. helical scan protocols, p < 0.001). The rate of downstream testing did not differ (13.8% vs. 15.9% for axial vs. helical scan protocols, p = 0.555). Conclusions: In patients with stable and low heart rates, the prospectively ECG-triggered axial scan protocol maintained image quality but reduced radiation exposure by 69% compared with helical scanning. Axial computed tomography data acquisition should be strongly recommended in suitable patients to avoid unnecessarily high radiation exposure. (Prospective Randomized Trial on Radiation Dose Estimates of CT Angiography in Patients Scanned With a Sequential Scan Protocol [PROTECTION-III]; NCT00612092)

CMR Imaging Assessing Viability in Patients With Chronic Ventricular Dysfunction Due to Coronary Artery Disease: A Meta-Analysis of Prospective Trials

Jorge Romero, Xiaonan Xue, Waddy Gonzalez, Mario J. Garcia — 2012-05-01

Objectives: The purpose of this study was to compare the diagnostic accuracy of cardiac magnetic resonance (CMR) assessing myocardial viability in patients with chronic left ventricular (LV) dysfunction due to coronary artery disease using 3 techniques: 1) end-diastolic wall thickness (EDWT); 2) low-dose dobutamine (LDD); and 3) contrast delayed enhancement (DE). Background: CMR has been proposed to assess myocardial viability over the past decade. However, the best CMR strategy to evaluate patients being contemplated for revascularization has not yet been determined. Some centers advocate DE CMR due to its high sensitivity to identify scar, whereas others favor the use of LDD CMR for its ability to identify contractile reserve. Methods: A systematic review of MEDLINE, Cochrane, and Embase for all the prospective trials assessing myocardial viability in subjects with chronic LV dysfunction using CMR was performed using a standard approach for meta-analysis for diagnostic tests and a bivariate analysis of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A total of 24 studies of CMR evaluating myocardial viability with 698 patients fulfilled the inclusion criteria. Eleven studies used DE, 9 studies used LDD, and 4 studies used EDWT. Our meta-analysis indicates that among CMR methods, DE CMR provides the highest sensitivity as well as the highest NPV (95% and 90%, respectively) for predicting improved segmental LV contractile function after revascularization, followed by EDWT CMR, whereas LDD CMR demonstrated the lowest sensitivity/NPV among all modalities. On the other hand, LDD CMR offered the highest specificity and PPV (91% and 93%, respectively), followed by DE CMR, whereas EDWT showed the lowest of these parameters. Conclusions: DE CMR provides the highest sensitivity and NPV, whereas LDD CMR provides the best specificity and PPV. In light of these findings, integrating these 2 methods should provide increased accuracy in evaluating patients with chronic LV dysfunction being considered for revascularization.

Myocardial Viability: Dead or Alive Is Not the Question!⁎

Eike Nagel, Andreas Schuster — 2012-05-01

When talking about viability—or better: hibernating myocardium—the question is not: “dead or alive,” the question is rather “what needs to be done to improve the patient's symptoms and prognosis.” Little is known to answer this question.

Diagnostic Performance of CMR Imaging Compared With EMB in Patients With Suspected Myocarditis

2012-05-01

Objectives: The goal of this study was to assess the diagnostic performance of cardiac magnetic resonance (CMR) compared with endomyocardial biopsy in patients with suspected acute myocarditis (AMC) and chronic myocarditis (CMC). Background: Several studies have reported an encouraging diagnostic performance of CMR in myocarditis. However, the comparison of CMR with clinical data only and the use of preselected patient populations are important limitations of the majority of these reports. Methods: One hundred thirty-two consecutive patients with suspected AMC (defined by symptoms ≤14 days; n = 70) and CMC (defined by symptoms >14 days; n = 62) were included. Patients underwent cardiac catheterization with left ventricular endomyocardial biopsy and CMR, including T2-weighted imaging for assessment of edema, T1-weighted imaging before and after contrast administration for evaluation of hyperemia, and assessment of late gadolinium enhancement. CMR results were considered to be consistent with the diagnosis of myocarditis if 2 of 3 CMR techniques were positive. Results: Within the total population, myocarditis was the most common diagnosis on endomyocardial biopsy analysis (62.9%). Viral genomes were detected in 30.3% (40 of 132) of patients within the total patient population and significantly more often in patients with AMC than CMC (40.0% vs. 19.4%; p = 0.013). For the overall cohort of patients with either suspected AMC or CMC, the diagnostic sensitivity, specificity, and accuracy of CMR were 76%, 54%, and 68%, respectively. The best diagnostic performance was observed in patients with suspected AMC (sensitivity, 81%; specificity, 71%; and accuracy, 79%). In contrast, diagnostic performance of CMR in suspected CMC was found to be unsatisfactory (sensitivity, 63%; specificity, 40%; and accuracy, 52%). Conclusions: The results of this study underline the usefulness of CMR in patients with suspected AMC. In contrast, the diagnostic performance of CMR in patients with suspected CMC might not be sufficient to guide clinical management.

CMR in Myocarditis: Valuable Tool, Room for Improvement⁎

Godtfred Holmvang, G. William Dec — 2012-05-01

Myocarditis can be difficult to diagnose due to varied clinical presentations, with onset ranging from insidious to acute. Endomyocardial biopsy has been the diagnostic “gold standard” but is now seldom used due to the invasive nature, high rate of sampling error, and variability in diagnostic criteria and interpretation.

Feasibility of [18F]-2-Fluoro-A85380-PET Imaging of Human Vascular Nicotinic Acetylcholine Receptors In Vivo

2012-05-01

Objectives: The aim of this feasibility study was to evaluate [18F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders. Background: [18F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls. Methods: [18F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [18F]-2-Fluoro-A85380 uptake in the arteries were also assessed. Results: [18F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [18F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together. Conclusions: [18F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature.

Imaging Vascular Nicotine Receptors: A New Window Onto Vascular Disease⁎

John P. Cooke — 2012-05-01

In the past 20 years, it has become increasingly apparent that nicotinic acetylcholine receptors (nAChRs) exist outside of the nervous system and neuromuscular junction (). These non-neuronal nAChRs play important roles in modulating the immune cell activation (), keratinocyte proliferation and migration (), and airway and bladder epithelial function (), as well as the adult and embryonic stem cell behavior and fate (). Furthermore, nAChRs expressed by tumor cells play a role in the progression of malignancy ().

High Platelet Reactivity on Clopidogrel Therapy Correlates With Increased Coronary Atherosclerosis and Calcification: A Volumetric Intravascular Ultrasound Study

2012-05-01

Objectives: This study sought to evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging. Background: Atherosclerosis progresses by the pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden. Methods: This study included patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y12 reaction units) performed >16 h after PCI, after the stabilization of clopidogrel therapy (administered before PCI). Platelet reactivity >230 P2Y12 reaction units defined high on-treatment platelet reactivity (HPR). Results: Among 335 patients (mean age 65.0 years, 71% men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, patients with HPR had significantly greater target lesion calcium lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume, and also greater luminal volume, despite similar plaque burden. By multivariate analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length, and calcium arc. Conclusions: Increased platelet reactivity on clopidogrel treatment, defined as >230 P2Y12 reaction units, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.

Is Viability Imaging Still Relevant in 2012?

Panithaya Chareonthaitawee, Bernard J. Gersh, Julio A. Panza — 2012-05-01

WITH THE PUBLICATION OF THE STICH (Surgical Treatment for Ischemic Heart Failure) trial () and the viability substudy (), questions have arisen regarding the utility of viability testing in patients with left ventricular systolic dysfunction and coronary artery disease (CAD) prior to revascularization decisions. Prior observational studies and meta-analyses () had suggested that those with viability demonstrated on noninvasive testing fared better with revascularization, whereas those without might fare worse.

Cell Tracking and the Development of Cell-Based Therapies: A View From the Cardiovascular Cell Therapy Research Network

2012-05-01

Cell-based therapies are being developed for myocardial infarction (MI) and its consequences (e.g., heart failure) as well as refractory angina and critical limb ischemia. The promising results obtained in preclinical studies led to the translation of this strategy to clinical studies. To date, the initial results have been mixed: some studies showed benefit, whereas in others, no benefit was observed. There is a growing consensus among the scientific community that a better understanding of the fate of transplanted cells (e.g., cell homing and viability over time) will be critical for the long-term success of these strategies and that future studies should include an assessment of cell homing, engraftment, and fate as an integral part of the trial design. In this review, different imaging methods and technologies are discussed within the framework of the physiological answers that the imaging strategies can provide, with a special focus on the inherent regulatory issues.

Multiplanar Visualization of Blood Flow Using Echocardiographic Particle Imaging Velocimetry

Partho P. Sengupta, Gianni Pedrizetti, Jagat Narula — 2012-05-01

echocardiographic particle imaging velocimetry (echo-piv) is a noninvasive technique where acoustic reflections from ultrasound contrast agents are tracked frame by frame for characterizing 2-dimensional cardiac and vascular flow fields. Three-dimensional asymmetries in flow sequence can be interpreted by using multiplanar reconstructions of echo-PIV images obtained by biplane echocardiography ( , Online Videos 1, 2, and 3). For example, the sequence of flow in a normal left ventricle (LV) ( , Online Video 4) is consistent with the formation of asymmetric toroidal vortex ring in early diastole (Online Video 5). The asymmetric vortex is cleared in systole as blood is ejected through a narrow jet in the LV outflow with surrounding shear layers ( , Online Video 4). Asymmetry of filling vortex and shear layers during ejection explain previously reported Doppler recordings of skewed velocity distributions in the LV cavity ( ). The left atrial (LA) flow ( , Online Video 6) illustrates the presence of multiple small circulating vortices. The jet from the right upper pulmonary vein passes peripherally along the wall with minimal entrainment. The vortices in the cavity vanish with the onset of mitral valve opening. The presence of multiple transient vortices in the normal subject may have beneficial effects in avoiding LA stasis in sinus rhythm. Flow in the descending thoracic aorta ( , Online Video 7) shows skewed axial velocity profiles. Although high velocity forward motion is underestimated, retrograde streaming in systole is visualized. In addition, strong secondary recirculating flows are seen in diastole. Presence of flow asymmetry and retrograde flow from descending thoracic aorta has been recently identified as a potential pathway for retrograde cerebral embolism of plaques formed in descending thoracic aorta ( ).

Platypnea-Orthodeoxia Syndrome Due to PFO and Aortic Dilation

Yasunaga Shiraishi, Daihiko Hakuno, Kikuo Isoda, Kouji Miyazaki, Takeshi Adachi — 2012-05-01

A 75-year-old man had occasionally been referred to our hospital with sudden dyspnea due to unknown causes. He had a history of hypertension and polycystic kidneys and had undergone transcatheter pulmonary vein isolation for paroxysmal atrial fibrillation 2 years previously. Physical examination revealed normal heart sounds without murmurs and was otherwise unremarkable. Electrocardiography, chest radiography, and blood tests were also normal. Oxygen saturation was 98% on room air in the supine position, but once he sat up, oxygen saturation suddenly dropped, causing dyspnea. He was then admitted for further investigation. Continuous oxygen saturation monitoring showed that it decreased negligibly during standing or walking but decreased strikingly to 72% just after sitting or squatting. Chest computed tomography, spirometry, and lung perfusion scintigraphy showed no findings of lung disease or pulmonary embolism. Transthoracic echocardiography showed dilation of the sinus of Valsalva and ascending aorta without abnormal shunting, pulmonary hypertension, or ventricular diastolic dysfunction.

Superior Doctor at a Point-of-Care: A Call to Change HF Management

Magdalena Lipczyńska, Piotr Szymański, Anna Klisiewicz, Piotr Hoffman — 2012-05-01

We read with great interest both the paper by Kalogeropoulos et al. () and the accompanying editorial by Abhayaratna () regarding the role of echocardiography and N-terminal pro–B-type natriuretic peptide (NT-proBNP) in screening for heart failure (HF).

Reply

2012-05-01

We thank Dr. Lipczyńska and colleagues for their interest in our work (). However, it is crucial to differentiate between the various uses of echocardiography in heart failure (HF). Our paper focuses on risk stratification for future clinical (stage C) HF and has implications for subclinical heart disease (stage B HF) screening (). Therefore, our inferences cannot be extrapolated to clinical HF, where assessment by echocardiography is a class I indication by most guidelines. The low rates of echocardiography referral for patients with suspected or confirmed HF among primary care physicians (PCPs) cannot be solely attributed to cost or limited access as implied. Delayed uptake of evidence-based practices among PCPs is a key factor. In IMPROVEMENT (Improvement programme in evaluation and management of heart failure) (), 82% of patients eventually had echocardiography despite 45% of PCPs recommending it, a discrepancy that is difficult to explain by waiting times or workforce distribution by that time (). In SHAPE (Study Group on HF Awareness and Perception in Europe), the disparities in HF management between internists, PCPs, and cardiologists extended to all evidence-based measures, pointing to gaps in provider education ().

Viability is in the Eye of the Beholder…

Christopher M. Kramer, Jagat Narula — 2012-05-01

The term myocardial “viability” in chronic left ventricular (LV) dysfunction due to coronary artery disease has been interpreted in multiple ways by clinicians and imagers alike. The classic definition assesses whether or not the myocardial tissue under consideration is alive or dead. However, more often we have used the term to address whether or not the tissue would recover function, especially after revascularization. The variability of imaging definitions of viability further adds to the problem. The imaging definition of viability depends upon the eye of the beholder. For example, an echocardiographer defines viability as a preserved contractile response to low doses of dobutamine (LDD) or inotropic reserve. Those performing single-photon emission computed tomography (SPECT) define viability by the absolute number of counts of myocardial perfusion tracers across a segment of myocardium, or by the demonstration of redistribution of radiotracer in the region of interest at rest. Positron emission tomography (PET) imaging defines viability as a metabolically active tissue with adequate uptake of 18fluorodeoxyglucose preferably in the presence of a severe reduction in blood flow. Cardiac magnetic resonance (CMR) identifies viability by documenting the lack of transmural scarring across the thickness of the myocardium—the less the transmurality of late gadolinium enhancement (LGE), the more viable the segment. In addition, inotropic reserve to LDD has also been evaluated by CMR as a marker of viability.

Reference Citations in iJACC: Litera Scripta Manet⁎

Thomas H. Marwick, Y. Chandrashekhar, Jagat Narula — 2012-05-01

The man who doesn't read has no advantage over the man who can't read. —Mark Twain, 1835–1910 () One of the most important but underappreciated and probably least discussed section of a paper is the list of references at the end. As Editors, we are occasionally reminded about how this section can raise issues for our decision-making. We are sometimes amazed at the rather superficial treatment accorded to this section; some papers come with too many and only remotely relevant citations and others come with too few citations, partially ignoring important previous work. References sometimes purport to be something they are not. More recently, we were even faced with a paper where we were admonished by an investigator who thought his seminal work was ignored in a paper we published. Creating the most suitable reference list is a delicate balance and there is not much discussion about it. Therefore, we address some of these issues as it pertains to iJACC.