JACC: Cardiovascular Imaging

Echocardiography, Natriuretic Peptides, and Risk for Incident Heart Failure in Older Adults: The Cardiovascular Health Study

2012-02-01

Objectives: This study sought to examine the potential utility of echocardiography and N-terminal pro–B-type natriuretic peptide (NT-proBNP) for heart failure (HF) risk stratification in concert with a validated clinical HF risk score in older adults. Background: Without clinical guidance, echocardiography and natriuretic peptides have suboptimal test characteristics for population-wide HF risk stratification. However, the value of these tests has not been examined in concert with a clinical HF risk score. Methods: We evaluated the improvement in 5-year HF risk prediction offered by adding an echocardiographic score and/or NT-proBNP levels to the clinical Health Aging and Body Composition (ABC) HF risk score (base model) in 3,752 participants of the CHS (Cardiovascular Health Study) (age 72.6 ± 5.4 years; 40.8% men; 86.5% white). The echocardiographic score was derived as the weighted sum of independent echocardiographic predictors of HF. We assessed changes in Bayesian information criterion (BIC), C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). We examined also the weighted NRI across baseline HF risk categories under multiple scenarios of event versus nonevent weighting. Results: Reduced left ventricular ejection fraction, abnormal E/A ratio, enlarged left atrium, and increased left ventricular mass were independent echocardiographic predictors of HF. Adding the echocardiographic score and NT-proBNP levels to the clinical model improved BIC (echocardiography: −43, NT-proBNP: −64.1, combined: −68.9; all p < 0.001) and C index (baseline: 0.746; echocardiography: +0.031, NT-proBNP: +0.027, combined: +0.043; all p < 0.01), and yielded robust IDI (echocardiography: 43.3%, NT-proBNP: 42.2%, combined: 61.7%; all p < 0.001), and NRI (based on Health ABC HF risk groups; echocardiography: 11.3%; NT-proBNP: 10.6%, combined: 16.3%; all p < 0.01). Participants at intermediate risk by the clinical model (5% to 20% 5-yr HF risk; 35.7% of the cohort) derived the most reclassification benefit. Echocardiography yielded modest reclassification when used sequentially after NT-proBNP. Conclusions: In older adults, echocardiography and NT-proBNP offer significant HF risk reclassification over a clinical prediction model, especially for intermediate-risk individuals.

Echocardiography for the “Superior Doctor” A Call to Action in the Management of Heart Failure⁎

Walter P. Abhayaratna — 2012-02-01

The superior doctor prevents sickness; the mediocre doctor attends to impending sickness; the inferior doctor treats actual sickness. —Extract from 1st Chinese Medical Text. Attributed to Huang Dee Nai-Chan, circa 2600 B.C. ()

Prediction of Coronary Artery Calcium Progression in Individuals With Low Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis

2012-02-01

Objectives: This study sought to determine whether novel markers not involving ionizing radiation could predict coronary artery calcium (CAC) progression in a low-risk population. Background: Increase in CAC scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in individuals with low predicted risk (Framingham Risk Score [FRS] <10%). Methods: From 6,814 participants in MESA (Multi-Ethnic Study of Atherosclerosis), 2,620 individuals were classified as low risk for CHD events (FRS <10%) and had follow-up CAC measurement. In addition to traditional risk factors (RFs), various combinations of novel marker models were selected on the basis of data-driven, clinical, or backward stepwise selection techniques. Results: Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1,830 with baseline CAC = 0 and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c statistic = 0.711) revealed improvements in discrimination of approximately only 0.005 each (c statistics 0.7158, 0.7160, and 0.7164) for the best-fit models. All 3 best-fit novel marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared with the lowest probability quartile groups (39.2% to 40.3% vs. 6.4% to 7.1%). Conclusions: In individuals at low predicted risk according to FRS, traditional risk factors predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.

A Quantitative Pixel-Wise Measurement of Myocardial Blood Flow by Contrast-Enhanced First-Pass CMR Perfusion Imaging: Microsphere Validation in Dogs and Feasibility Study in Humans

Li-Yueh Hsu, Daniel W. Groves, Anthony H. Aletras, Peter Kellman, Andrew E. Arai — 2012-02-01

Objectives: The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. Background: Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. Methods: First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. Results: Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bull's-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p < 0.001 and p < 0.01, respectively). Conclusions: Myocardial blood flow can be quantified at the pixel level (∼32 μl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.

Do We Need a New Prescription to View Myocardial Perfusion?⁎

Michael Jerosch-Herold, Otavio R. Coelho-Filho — 2012-02-01

The paper by Hsu et al. () in this issue of iJACC presents the results of a validation study on the use of cardiac magnetic resonance (CMR) imaging to map myocardial blood flow (MBF) at the spatial resolution of the underlying images (“pixel-wise”), acquired during the first pass of a gadolinium contrast bolus injection. This work raises 2 interesting questions: do we need pixel-level resolution for mapping MBF, despite the prevalent use of simpler and robust methods, which are exemplified by the bull's-eye plot, well known from nuclear cardiac imaging? And, what is to be gained by mapping, not just the relative distribution of blood flow, but also the absolute MBF in units of milliliters/minute/gram of tissue? Though the study by Hsu et al. () did not try to explicitly address these questions, the longer-term, clinical application, and significance of the reported technique depends on how these questions are answered.

Impact of Statin Therapy on Plaque Characteristics as Assessed by Serial OCT, Grayscale and Integrated Backscatter–IVUS

2012-02-01

Objectives: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. Background: Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. Methods: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. Results: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (−6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. Conclusions: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

Resolution of Inflammation, Statins, and Plaque Regression⁎

Pedro R. Moreno, Annapoorna Kini — 2012-02-01

The success of aggressive pharmacological therapy in the prevention and treatment of cardiovascular disease continues to give us renovated energy and constructive hope. Within the last decade, the incidence of acute myocardial infarction in the U.S. population showed a steady decrease. Ten years ago, in 2002, the annual hospitalization rate was 1,131 per 100,000 Medicare beneficiaries. This number fell to 866 in 2007, a 23% decline (). Other studies have confirmed this observation (), with an impressive 31% reduction in death attributable to cardiovascular disease from 1998 to 2008 (). Despite these improvements, cardiovascular disease continues to be the major cause of death in developed countries, and atherothrombosis is responsible for the majority of these events.

Determinants and Functional Significance of Myocardial Perfusion Reserve in Severe Aortic Stenosis

2012-02-01

Objectives: The purpose of this study was to assess the functional significance of cardiac magnetic resonance (CMR) measures of left ventricular (LV) remodeling and myocardial perfusion reserve (MPR) in patients with severe aortic stenosis (AS), without obstructive coronary artery disease. Background: Measures of stenosis severity do not correlate well with exercise intolerance in AS. LV remodeling in AS is associated with myocardial fibrosis and impaired MPR. The functional significance and determinants of MPR in AS are unclear. Methods: Forty-six patients with isolated severe AS were prospectively studied before aortic valve replacement. The following investigations were undertaken: cardiopulmonary exercise testing to measure aerobic exercise capacity (peak VO2); CMR to assess left ventricular mass index (LVMI), myocardial fibrosis with late gadolinium enhancement (LGE), myocardial blood flow (MBF), and MPR; and transthoracic echocardiography to assess stenosis severity and diastolic function. Results: Peak VO2 was associated with sex (β = −0.41), age (β = −0.32), MPR (β = 0.45), resting MBF (β = −0.53), and septal transmitral flow velocity to annular velocity ratio (E/E′) (β = −0.34), but not with LVMI, LGE, or echocardiographic measures of AS severity. On stepwise regression analysis, only MPR was independently associated with age- and sex-corrected peak VO2 (β = 0.46, p = 0.001). MPR was also inversely related to New York Heart Association functional class (p = 0.001). Univariate associations with MPR were sex (β = 0.38, p = 0.02), septal E/E′ (β = −0.30, p = 0.03), peak aortic valve velocity (β = −0.34, p = 0.02), LVMI (β = −0.51, p < 0.001), and LGE category (β = −0.46, p = 0.002). On multivariate analysis, LVMI and LGE were independently associated with MPR. Conclusions: CMR-quantified MPR is independently associated with aerobic exercise capacity in severe AS. LV remodeling appears to be a more important determinant of impaired MPR than stenosis severity per se. Further work is required to determine how CMR assessment of MPR can aid clinical management of patients with AS.

Imaging in Aortic Stenosis—Let the Data Talk⁎

K. Lance Gould, Nils P. Johnson — 2012-02-01

Physiology plays an increasingly clinical role in cardiology. In this issue of iJACC, Steadman et al. () reflect this trend with their report on myocardial perfusion in aortic stenosis (AS) using cardiac magnetic resonance.

Is Discordance of Coronary Flow Reserve and Fractional Flow Reserve Due to Methodology or Clinically Relevant Coronary Pathophysiology?

Nils P. Johnson, Richard L. Kirkeeide, K. Lance Gould — 2012-02-01

Objectives: The purpose of this study was to determine whether observed discordance between coronary flow reserve (CFR) and fractional flow reserve (FFR) is due to methodology or reflects basic coronary pathophysiology. Background: Despite the clinical importance of coronary physiological assessment, relationships between its 2 most common tools, CFR and FFR, remain poorly defined. Methods: The worst CFR and stress relative uptake were recorded from 1,500 sequential cardiac positron emission tomography cases from our center. From the literature, we assembled all combined, invasive CFR-FFR measurements, including a subset before and after angioplasty. Both datasets were compared with a fluid dynamic model of the coronary circulation predicting relationships between CFR and FFR for variable diffuse and focal narrowing. Results: A modest but significant linear relationship exists between CFR and FFR both invasively (r = 0.34, p < 0.001) and using positron emission tomography (r = 0.36, p < 0.001). Most clinical patients undergoing CFR or FFR measurements have diffusely reduced CFR consistent with diffuse atherosclerosis or small-vessel disease. The theoretical model predicts linear relationships between CFR and FFR for progressive stenosis with slopes dependent on diffuse narrowing, matching observed data. Reported changes in CFR and FFR with angioplasty agree with model predictions of removing focal stenosis but leaving diffuse disease. Although CFR-FFR concordance is common, discordance is due to dominant or absent diffuse versus focal disease, reflecting basic pathophysiology. Conclusions: CFR is linearly related to FFR for progressive stenosis superimposed on diffuse narrowing. The relative contributions of focal and diffuse disease define the slope and values along the linear CFR and FFR relationship. Discordant CFR and FFR values reflect divergent extremes of focal and diffuse disease, not failure of either tool. With such discordance observed by invasive and noninvasive techniques and also fitting fluid dynamic predictions, it reflects clinically relevant basic coronary pathophysiology, not methodology.

FFR and Coronary Flow Reserve: Friends or Foes?⁎

Heinrich R. Schelbert — 2012-02-01

The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study has re-emphasized the importance of assessing functional consequences of coronary stenoses (). In that multicenter trial involving 1,005 patients with multivessel coronary artery disease (CAD), percutaneous coronary interventions (PCI) guided by functional assessments of coronary stenoses was associated with a significantly lower 2-year morbidity and mortality as compared to PCI guided only by coronary anatomy (). The functional assessments were based on the fractional flow reserve (FFR), an invasive approach, which measures the stenosis-related decline in distal coronary pressure during maximum hyperemia. The normal coronary vessel exerts little if any resistance to flows even during hyperemia, so that the coronary pressure is fully maintained throughout the length of the epicardial coronary artery and the distal coronary pressure equals the central aortic pressure. In the presence of a focal coronary stenosis, however, the distal coronary pressure declines during hyperemia as a function of the stenosis severity; stenoses with FFRs <0.75 or <0.80 have been shown to induce ischemia and, hence, are defined as functionally significant. Methodologically, the FFR depends only on the distal to proximal pressure difference in the coronary vessel. The index is relatively independent of heart rate and blood pressure (). It thus differs from other measures of functional significance of coronary stenosis like the coronary flow reserve (CFR) or stress-rest myocardial perfusion imaging (MPI), which compare hyperemic to resting flows or evaluate the effects of coronary stenosis on the relative distribution of myocardial blood flow.

Delayed-Enhanced MR Scar Imaging and Intraprocedural Registration Into an Electroanatomical Mapping System in Post-Infarction Patients

2012-02-01

Post-infarction arrhythmias are most often confined to scar tissue. Scar can be detected by delayed-enhanced cardiac magnetic resonance. The purpose of this study was to assess the feasibility of pre-procedural scar identification and intraprocedural real-time image registration with an electroanatomical map in 23 patients with previous infarction and ventricular arrhythmias (VAs). Registration accuracy and cardiac magnetic resonance/electroanatomical map correlations were assessed, and critical areas for VA were correlated with the presence of scar. With a positional registration error of 3.8 ± 0.8 mm, 86% of low-voltage points of the electroanatomical map projected onto the registered scar. The delayed-enhanced cardiac magnetic resonance–defined scar correlated with the area of low voltage (R = 0.82, p < 0.001). All sites critical to VAs projected on the registered scar. Selective identification and extraction of delayed-enhanced cardiac magnetic resonance defined scar followed by registration into a real-time mapping system are feasible and help to identify and display the arrhythmogenic substrate in post-infarction patients with VAs.

Integration of CMR Scar Imaging and Electroanatomic Mapping: The Future of VT Ablation?⁎

Kenneth C. Bilchick — 2012-02-01

In this issue of iJACC, Gupta et al. () present their single-center experience with intraprocedural 3-dimensional registration of cardiac magnetic resonance (CMR) scar mapping with voltage maps created at the time of ablation of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in 23 post-infarction patients. The methodology involves using 3 standard landmarks—the aortic root, mitral annulus plane, and left ventricular apex—to integrate voltage and scar maps, which allows more focused mapping of VT in areas with scar. Although there is previous experience with post hoc integration of CMR scar and voltage maps (), the novel feature of this contribution is the use of this methodology to guide the VT ablation procedure. At the same time, the study raises several questions. First, is this methodology likely to improve the efficiency and success rates of VT ablation in the future? Second, does this methodology have the potential to be applied broadly to most patients undergoing VT ablation? Third, are there other imaging techniques likely to be more effective or more broadly applicable for patients undergoing VT ablation?

Targeted Metabolic Imaging to Improve the Management of Heart Disease

Moritz Osterholt, Shiraj Sen, Vasken Dilsizian, Heinrich Taegtmeyer — 2012-02-01

Tracer techniques are powerful methods for assessing rates of biological processes in vivo. A case in point is intermediary metabolism of energy providing substrates, a central feature of every living cell. In the heart, the tight coupling between metabolism and contractile function offers an opportunity for the simultaneous assessment of cardiac performance at different levels in vivo: coronary flow, myocardial perfusion, oxygen delivery, metabolism, and contraction. Noninvasive imaging techniques used to identify the metabolic footprints of either normal or perturbed cardiac function are discussed.

CMR for the Diagnosis of Right Heart Disease

Timothy A. Fairbairn, Manish Motwani, John P. Greenwood, Sven Plein — 2012-02-01

Right heart disease can present a clinical diagnostic conundrum as a number of pathologies can present with a variety of often nonspecific symptoms. Transthoracic echocardiography (TTE) remains the main noninvasive diagnostic imaging test for right heart disease, yet it has several limitations. Visualization of the right ventricular (RV) free wall and its trabeculations by TTE can be difficult, with no accurate method of quantifying RV volumes and function. Cardiac magnetic resonance (CMR) allows more reliable assessment of the right heart because of its unrestricted field of view and free and reproducible imaging planes. Therefore, CMR is considered the reference standard for the calculation of right heart volumes, mass, and function. In addition, the multiparametric properties of CMR allow for tissue characterization to aid the differential diagnosis of right heart pathologies, as demonstrated in this case series ().

Mechanism of Asymmetric Leaflet Tethering in Ischemic Mitral Regurgitation: 3D Analysis With Multislice CT

2012-02-01

It has been reported that patients with ischemic mitral regurgitation (IMR) caused by inferoposterior myocardial infarction have asymmetric leaflet tethering associated with regional and inferior left ventricular (LV) remodeling (). This report suggests that asymmetric medial papillary muscle (PM) displacement with inferior myocardial infarction causes asymmetric leaflet tethering in the medial side of the whole leaflets. However, asymmetric leaflet tethering accompanied by regional LV dilation in patients with functional mitral regurgitation (FMR) has not been well investigated.

OCT-Verified Neointimal Hyperplasia Is Increased at Fracture Site in Drug-Eluting Stents

2012-02-01

Although drug-eluting stents dramatically reduce stent restenosis, in-stent restenosis still occurs in approximately 10% of sirolimus-eluting stent (SES) implantation cases. Optical coherence tomography (OCT) has the potential to assess neointima hyperplasia precisely in vivo (). However, the morphological features of stent fracture in OCT imaging have not yet been reported, and there is no OCT study that clarifies the relationship between stent fracture and neointimal hyperplasia in SES. We investigated the morphological features of stent fracture in OCT to clarify the relationship between stent fracture and neointimal hyperplasia in SES.

T2-Weighted CMR: But Where Is Elvis in the End?

Nathan Mewton, Franck Thuny, Pierre Croisille — 2012-02-01

A few months ago, in an editorial by Raman et al. (), T2-weighted (T2w) short tau inversion recovery (STIR) imaging, the only validated T2 sequence that was tested against pathology in an experimental setting to assess the myocardial area at risk (AAR), was almost thrown out the window because of its limited accuracy and poor reproducibility due to the high sensitivity to artifacts. However, there was still hope, because better sequences have come out (T2w ACUTE [Acquisition for Cardiac Unified T2 Edema], T2prep steady-state free precession, T2 mapping) with significantly better reproducibility and accuracy. But those sequences have not been validated against pathology.

Reply

Matthias G. Friedrich — 2012-02-01

We thank Dr. Mewton and colleagues for their interest in our paper () and applaud them for raising an important point concerning the validity of current T2-weighted CMR imaging to visualize the area at risk in reperfused myocardial infarction (MI).

Reply

Han W. Kim, Raymond J. Kim — 2012-02-01

We thank Dr. Mewton and colleagues for adding to the discussion regarding T2-weighted cardiac magnetic resonance (CMR). Often, a candid debate will invoke strong reactions, but we are hopeful that readers of our Pro/Con article () with Dr. Friedrich will carefully consider the merits of the respective arguments. Here, we present our perspective on the issues raised by Dr. Mewton and colleagues.

CMR-Based Quantitative Myocardial Perfusion: Pixel-Wise and Pound-Wise

Christopher M. Kramer, Y. Chandrashekhar, Jagat Narula — 2012-02-01

Quantitative measurement of myocardial perfusion has been a goal of cardiovascular investigators for a number of years. Positron emission tomography (PET) has allowed assessment of myocardial blood flow in absolute value (milliliters per gram per minute) () and is accurate at identifying both flow-limiting epicardial coronary artery disease (CAD) as well as microvascular abnormalities. Qualitative cardiac magnetic resonance (CMR) stress perfusion has also made clinical inroads of late, demonstrating higher sensitivity and negative predictive value than single-photon emission computed tomography (SPECT) in a head-to-head comparison of symptomatic patients against x-ray coronary angiography employed as the reference standard (). Although the feasibility is established the more important question is if we could do better with absolute quantitation of myocardial blood flow? A recent comparative study of qualitative versus quantitative analysis of myocardial blood flow reserve with CMR did not demonstrate any incremental value of quantitative assessment for the overall per patient accuracy, and this approach may be reasonable if the goal is to identify a patient with ischemia significant for justification of mechanical intervention (). However, the quantitative approach was more accurate for the assessment of pathophysiology in more detail such as the delineation of the amount of myocardium at jeopardy.