Akhil Narang

Regadenoson cardiovascular magnetic resonance myocardial perfusion imaging predicts need for future revascularization

Summary Regadenoson is a new vasodilator myocardial stress agent that is easier-to-use and more tolerable than adenosine. We demonstrate that, in patients undergoing cardiovascular magnetic resonance myocardial perfusion imaging, regadenoson is safe and effective in producing hyperemia and identifying the need for future revascularization. Background Regadenoson (Lexiscan; Astellas) is a new vasodilator myocardial stress agent that selectively activates the A2A receptor. Unlike adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear myocardial perfusion imaging (MPI), its performance in cardiovascular magnetic resonance (CMR) MPI remains unknown. The aim of this study was to assess the safety and tolerability of regadenoson and determine its ability to produce hyperemia and predict subsequent coronary revascularization in patients undergoing CMR-MPI. Methods 120 patients were prospectively enrolled to receive CMR-MPI (Achieva, Philips 1.5T) with regadenoson. Patients with contraindications to CMR-MPI or regadenoson were excluded. Short-axis slices were obtained at three levels of the left ventricle (LV) during first pass of Gadolinium-DTPA(0.075 mmol/kg at 4 ml/sec) for 50 consecutive heart beats. Images were acquired using a hybrid gradient echo/echo planar imaging sequence. Imaging was performed 1 minute after injection of regadenoson (0.4mg) and then repeated 15 minutes after injection of aminophylline (125mg) under resting conditions. Perfusion defects were defined as subendocardial hypointensity in a coronary distribution at stress, involving ≥25% wall thickness, and persisting for ≥ 2h eart beats following peak enhancement of the LV cavity. In a subgroup of patients (n=99), custom software was used to generate time intensity curves and to compare the myocardial upslope of the midventricular slice during stress and rest. All subjects were followed for 3 months for the occurrence of coronary revascularization. Results Overall, 51/120 (43%) of patients were female with an average age of 55±15 years and body mass index of 29 ±6 kg/m2. Baseline patient characteristics include: coronary artery disease (33%), diabetes (38%), hypertension (56%), and hypercholesterolemia (95%). The average resting blood pressure and heart rate were 124/ 61mmHg and 70bpm, respectively. Peak heart rate after regadenoson administration was 98bpm (p<0.001). Most patients (87%) experienced side effects from regadenoson including shortness of breath (34%), flushing (23%), and chest discomfort (17%). No EKG changes or residual side effects persisted in any patient at completion of study. The average myocardial upslope increased significantly between rest and stress conditions (9.1±5.9 vs. 12.8±8.1, p<0.001), reflecting the expected hyperemic effect of regadenoson. Perfusion defects were visually apparent in 33/120 (28%) patients. Revascularization occurred in 8/120 (7%) patients (Figure 1). The presence

Large high-density lipoprotein particle number is independently associated with microvascular function in patients with well-controlled low-density lipoprotein concentration: A vasodilator stress magnetic resonance perfusion study

BACKGROUND Abnormalities in total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides are associated with microvascular dysfunction. Recent studies suggest that lipid subfractions better predict atherogenic burden than a routine lipid panel. We sought to determine, whether lipid subfractions are more strongly associated with microvascular function and subclinical atherosclerosis, than conventional lipid measurements using vasodilator stress cardiovascular magnetic resonance (CMR). METHODS Twenty-four adults referred for risk stratification from a lipid clinic with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL underwent vasodilator CMR. Time-intensity curves generated from stress and rest perfusion images were used to determine the area under the curve (AUC) for the mid-ventricular slice myocardium and the left ventricular (LV) cavity. Myocardial perfusion reserve index (MPRi) was defined as stress to rest ratio of mid-ventricular myocardium AUC, normalized to LV cavity AUC. Lipid panels that included subfractions of LDL and high-density lipoprotein (HDL) were measured using nuclear magnetic resonance testing. The association between MPRi and lipid parameters was examined using univariate linear regression; lipid components statistically correlated with MPRi (P < .05) were then subjected to multivariate analysis. RESULTS Univariate regression analysis showed MPRi was associated with HDL-C, triglycerides, large HDL-P, and small LDL-P; no association was found between MPRi and total cholesterol, LDL-C, total LDL-P, or total HDL-P. Using multivariate analysis, large HDL-P was independently associated with MPRi. CONCLUSIONS In patients with LDL-C <100 mg/dL, large HDL-P is independently associated with CMR-derived myocardial perfusion reserve, a surrogate for microvascular function and subclinical atherosclerosis. Further studies using lipid subfractions to better understand cardiovascular risks are warranted.

Severe Torsades de Pointes with acquired QT prolongation

Torsades de pointes (TdP) is a fatal polymorphic ventricular tachycardia in association with congenital or acquired QT prolongation. Concomitant electrolyte disturbances and drugs potentiate the development of TdP. We describe a severe case of refractory TdP in the setting of methadone, cocaine, hypokalemia and hypomagnesemia. The successful treatment was achieved with the administration of magnesium, isoproterenol, and electrolyte replacement.

Evidence from a multicenter CMR registry indicates that stress CMR imaging provides highly effective risk stratification in patients suspected to have myocardial ischemia

Methods In 2006, we developed a web-based multicenter registry (CMR-Cooperative, CMRCOOP) specific for performance of clinical CMR. This registry aimed to standardize imaging protocol, collection of clinical data, data interpretation, and reporting. All patient identifying information was encrypted. All data was stored and protected by intranet servers and site-specific administrative access. We identified patients who were referred for vasodilating CMR studies with suspected ischemia from 3 major CMR and 1 European centers. Presence of > 1 segment of abnormal stress perfusion without LGE defines ischemia presence and the number of ischemic segments defines ischemia extent. Major hard outcomes (MACE) including all-cause mortality and acute MI were assessed and were associated with CMR evidence of ischemia, using Cox regression.

A New Educational Framework to Improve Lifelong Learning for Cardiologists

Lifelong learning is essential for the practicing cardiologist. Present lifelong learning mechanisms are stagnant and at risk for not meeting the needs of currently practicing cardiologists. With the increasing burden of cardiovascular disease, growing complexity of patient care, and ongoing pressures of nonclinical responsibilities, educational programming must evolve to meet the demands of the contemporary cardiovascular professional. A paradigm shift, replete with modern and practical educational tools, is needed in the lifelong learning armamentarium. Emerging evidence of novel educational strategies in graduate medical education supports the promise of broader application of these tools to different stages of professional life. In this commentary from the Fellows-in-Training Section Leadership Council, the authors propose 3 novel educational tools-personalized learning, adaptive learning, and the flipped classroom-to improve lifelong learning to meet the educational needs of fellows-in-training to practicing cardiologists alike.

Diagnosis of Isolated Cleft Mitral Valve Using Three-Dimensional Echocardiography

Background: The prevalence of isolated cleft mitral valve (MV; no concomitant congenital heart disease or degenerative MV disease) with significant mitral regurgitation (MR) diagnosed using two‐dimensional echocardiography (2DE) has been reported to be very low. Three‐dimensional echocardiography (3DE) has enabled a more comprehensive visualization of the MV and detailed understanding of the mechanisms of MR and can potentially reveal isolated cleft MV that is not recognized with 2DE. The aim of this study was to determine, using 3DE, the prevalence, location, and associated MV annular and left ventricular characteristics of isolated cleft MV, in the absence of associated congenital heart disease, in patients with significant MR. Methods: A total of 1,092 patients with unexplained moderate or greater MR on two‐dimensional transthoracic echocardiography who were referred for three‐dimensional transesophageal echocardiography between 2005 and 2017 (n = 626) were retrospectively studied. Left ventricular dimensions and function were determined, and quantitative MR assessment and three‐dimensional analysis of the MV annulus was performed. Results: Twenty‐one patients (prevalence 3.3%) were diagnosed with isolated cleft MV using three‐dimensional transesophageal echocardiography but not 2DE. The majority of these patients (n = 16) were noted to have anterior cleft MVs, with most located in the mid‐A1 (n = 10) or mid‐A3 (n = 5) scallops. Posterior clefts were less common (n = 5) and occurred at the site of the natural scallop indentations (three between P1 and P2 and two between P2 and P3). Among patients with either anterior or posterior MV cleft, there were no differences in left ventricular ejection fraction or three‐dimensional MV geometry (annular distance, height, circumference, and area). There was a trend toward worse MR severity in patients with anterior cleft MV. Conclusions: In patients with otherwise unexplained significant MR referred for transesophageal echocardiography, 3DE uncovered a considerably higher prevalence of isolated cleft MV than previously reported by 2DE, with the majority located in the anterior MV. Although the annular geometry was similar between patients with anterior and posterior cleft MVs, a trend toward more severe MR in anterior clefts may reflect underlying abnormalities in the embryologic development of the anterior MV leaflet. Evaluation of MV pathology is improved by 3DE, which should be used routinely in the setting significant MR. HIGHLIGHTSUsing 3DE, isolated cleft MV is more prevalent than previously reported.The majority of isolated cleft MV are located on the anterior MV leaflet.Patients with isolated cleft MV on the anterior leaflet tend to have more MR.3DE should be utilized when evaluating patients with MR of unclear etiology.

Fusion of Three-Dimensional Echocardiographic Regional Myocardial Strain with Cardiac Computed Tomography for Noninvasive Evaluation of the Hemodynamic Impact of Coronary Stenosis in Patients with Chest Pain

Background Combined evaluation of coronary stenosis and the extent of ischemia is essential in patients with chest pain. Intermediate‐grade stenosis on computed tomographic coronary angiography (CTCA) frequently triggers downstream nuclear stress testing. Alternative approaches without stress and/or radiation may have important implications. Myocardial strain measured from echocardiographic images can be used to detect subclinical dysfunction. The authors recently tested the feasibility of fusion of three‐dimensional (3D) echocardiography–derived regional resting longitudinal strain with coronary arteries from CTCA to determine the hemodynamic significance of stenosis. The aim of the present study was to validate this approach against accepted reference techniques. Methods Seventy‐eight patients with chest pain referred for CTCA who also underwent 3D echocardiography and regadenoson stress computed tomography were prospectively studied. Left ventricular longitudinal strain data (TomTec) were used to generate fused 3D displays and detect resting strain abnormalities (RSAs) in each coronary territory. Computed tomographic coronary angiographic images were interpreted for the presence and severity of stenosis. Fused 3D displays of subendocardial x‐ray attenuation were created to detect stress perfusion defects (SPDs). In patients with stenosis >25% in at least one artery, fractional flow reserve was quantified (HeartFlow). RSA as a marker of significant stenosis was validated against two different combined references: stenosis >50% on CTCA and SPDs seen in the same territory (reference standard A) and fractional flow reserve < 0.80 and SPDs in the same territory (reference standard B). Results Of the 99 arteries with no stenosis >50% and no SPDs, considered as normal, 19 (19%) had RSAs. Conversely, with stenosis >50% and SPDs, RSAs were considerably more frequent (17 of 24 [71%]). The sensitivity, specificity, and accuracy of RSA were 0.71, 0.81, and 0.79, respectively, against reference standard A and 0.83, 0.81, and 0.82 against reference standard B. Conclusions Fusion of CTCA and 3D echocardiography–derived resting myocardial strain provides combined displays, which may be useful in determination of the hemodynamic or functional impact of coronary abnormalities, without additional ionizing radiation or stress testing. HighlightsWe studied patients with chest pain.CT angiography fusion with 3D echocardiography derived resting myocardial strain.Strain abnormalities correlated with perfusion defects on vasodilator stress CT.Strain abnormalities correlated with reduced noninvasive fractional flow reserve.Image fusion may help determine the hemodynamic impact of coronary artery disease.

Machine learning based automated dynamic quantification of left heart chamber volumes

AIMS Studies have demonstrated the ability of a new automated algorithm for volumetric analysis of 3D echocardiographic (3DE) datasets to provide accurate and reproducible measurements of left ventricular and left atrial (LV, LA) volumes at end-systole and end-diastole. Recently, this methodology was expanded using a machine learning (ML) approach to automatically measure chamber volumes throughout the cardiac cycle, resulting in LV and LA volume-time curves. We aimed to validate ejection and filling parameters obtained from these curves by comparing them to independent well-validated reference techniques. METHODS AND RESULTS We studied 20 patients referred for cardiac magnetic resonance (CMR) examinations, who underwent 3DE imaging the same day. Volume-time curves were obtained for both LV and LA chambers using the ML algorithm (Philips HeartModel), and independently conventional 3DE volumetric analysis (TomTec), and CMR images (slice-by-slice, frame-by-frame manual tracing). Automatically derived LV and LA volumes and ejection/filling parameters were compared against both reference techniques. Minor manual correction of the automatically detected LV and LA borders was needed in 4/20 and 5/20 cases, respectively. Time required to generate volume-time curves was 35 ± 17 s using ML algorithm, 3.6 ± 0.9 min using conventional 3DE analysis, and 96 ± 14 min using CMR. Volume-time curves obtained by all three techniques were similar in shape and magnitude. In both comparisons, ejection/filling parameters showed no significant inter-technique differences. Bland-Altman analysis confirmed small biases, despite wide limits of agreement. CONCLUSION The automated ML algorithm can quickly measure dynamic LV and LA volumes and accurately analyse ejection/filling parameters. Incorporation of this algorithm into the clinical workflow may increase the utilization of 3DE imaging.

IMPLEMENTATION OF A WIDEBAND LATE GADOLINIUM ENHANCEMENT CARDIAC MAGNETIC RESONANCE PROTOCOL TO IMPROVE ASSESSMENT OF MYOCARDIAL SCAR IN PATIENTS WITH IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

Background: Severe susceptibility artifacts (SA) limit the use of cardiac magnetic resonance (CMR) in patients with implantable cardioverter defibrillators (ICDs). The use of a previously developed wideband (WB) late gadolinium enhancement (LGE) technique may ameliorate these artifacts. We sought to

Diagnostic usefulness of myocardial perfusion imaging in patients reluctant to undergo angiography

Patients with known or suspected coronary artery disease are often referred for isch- emic testing to aid in risk assessment and guide management when symptoms develop. Invasive coronary angiography and percutaneous intervention are typically reserved for patients with symptoms refractory to medical management. The use of noninvasive modalities with myocardial perfusion imaging is a powerful diagnostic and prognostic tool for patients reluctant to undergo angiography. This review focuses on evaluation of coronary artery disease with myocardial perfusion imaging using single-photon emission computerized tomography, positron emission tomography, myocardial contrast echocardiography, cardiovascular magnetic resonance, and cardiovascular computerized tomography.