Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.

Integrating Cardiac MRI Imaging and Multidisciplinary Clinical Care is Associated With Improved Outcomes in Patients With Fabry Disease.

Given the inherent complexities of Fabry disease (FD) and evolving landscape of cardiovascular clinical management, there is no established ideal clinical care model for these patients. We identified clinical factors predictive of increased risk of major adverse cardiac events (MACE) in patients with FD targeted to improve clinical outcomes. Ninety-five patients studied over a median follow-up time of 6.3 years, and 26 patients reached the composite endpoint with a high prevalence of heart failure and cerebrovascular events and no cardiac-related mortality. Patients with MACE had worse health-related quality of life scores. Hypertrophy and presence of myocardial fibrosis increase risk of MACE by 4-5 times, and dyslipidemia increases risk of MACE by 3 times. Early Fabry-specific treatment and close monitoring of comorbidities reduce cardiac complications and mortality. These findings highlight the importance of comprehensive multidisciplinary management to help improve outcomes in FD patients.

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis.

BACKGROUND: Quantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). METHODS: Consecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. RESULTS: Seventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. CONCLUSION: CPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging-Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy-Naïve Cancer.

Background The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance-based evaluation of cardiac health in patients with chemotherapy-naïve cancer with comparison with a healthy volunteer population. Methods and Results Three-hundred and eighty-one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three-dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak-systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex-matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters. Conclusions The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient's body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = -0.648, p < 0.001), RF (R = -0.441, p < 0.001), and stasis (R = -0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

Neural-Network-Based Diagnosis Using 3-Dimensional Myocardial Architecture and Deformation: Demonstration for the Differentiation of Hypertrophic Cardiomyopathy.

The diagnosis of cardiomyopathy states may benefit from machine-learning (ML) based approaches, particularly to distinguish those states with similar phenotypic characteristics. Three-dimensional myocardial deformation analysis (3D-MDA) has been validated to provide standardized descriptors of myocardial architecture and deformation, and may therefore offer appropriate features for the training of ML-based diagnostic tools. We aimed to assess the feasibility of automated disease diagnosis using a neural network trained using 3D-MDA to discriminate hypertrophic cardiomyopathy (HCM) from its mimic states: cardiac amyloidosis (CA), Anderson-Fabry disease (AFD), and hypertensive cardiomyopathy (HTNcm). 3D-MDA data from 163 patients (mean age 53.1 ± 14.8 years; 68 females) with left ventricular hypertrophy (LVH) of known etiology was provided. Source imaging data was from cardiac magnetic resonance (CMR). Clinical diagnoses were as follows: 85 HCM, 30 HTNcm, 30 AFD, and 18 CA. A fully-connected-layer feed-forward neural was trained to distinguish HCM vs. other mimic states. Diagnostic performance was compared to threshold-based assessments of volumetric and strain-based CMR markers, in addition to baseline clinical patient characteristics. Threshold-based measures provided modest performance, the greatest area under the curve (AUC) being 0.70. Global strain parameters exhibited reduced performance, with AUC under 0.64. A neural network trained exclusively from 3D-MDA data achieved an AUC of 0.94 (sensitivity 0.92, specificity 0.90) when performing the same task. This study demonstrates that ML-based diagnosis of cardiomyopathy states performed exclusively from 3D-MDA is feasible and can distinguish HCM from mimic disease states. These findings suggest strong potential for computer-assisted diagnosis in clinical practice.

Cardiovascular toxicity of PI3Kα inhibitors.

The phosphoinositide 3-kinases (PI3Ks) are a family of intracellular lipid kinases that phosphorylate the 3'-hydroxyl group of inositol membrane lipids, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. This results in downstream effects, including cell growth, proliferation, and migration. The heart expresses three PI3K class I enzyme isoforms (α, ß, and γ), and these enzymes play a role in cardiac cellular survival, myocardial hypertrophy, myocardial contractility, excitation, and mechanotransduction. The PI3K pathway is associated with various disease processes but is particularly important to human cancers since many gain-of-function mutations in this pathway occur in various cancers. Despite the development, testing, and regulatory approval of PI3K inhibitors in recent years, there are still significant challenges when creating and utilizing these drugs, including concerns of adverse effects on the heart. There is a growing body of evidence from preclinical studies revealing that PI3Ks play a crucial cardioprotective role, and thus inhibition of this pathway could lead to cardiac dysfunction, electrical remodeling, vascular damage, and ultimately, cardiovascular disease. This review will focus on PI3Kα, including the mechanisms underlying the adverse cardiovascular effects resulting from PI3Kα inhibition and the potential clinical implications of treating patients with these drugs, such as increased arrhythmia burden, biventricular cardiac dysfunction, and impaired recovery from cardiotoxicity. Recommendations for future directions for preclinical and clinical work are made, highlighting the possible role of PI3Kα inhibition in the progression of cancer-related cachexia and female sex and pre-existing comorbidities as independent risk factors for cardiac abnormalities after cancer treatment.

Determinants and Prognostic Significance of Serial Right Heart Function Changes in Patients With Cardiac Amyloidosis.

BACKGROUND: Right heart function is an important prognostic determinant in cardiac amyloidosis. In this study we characterized serial changes in right and left heart function and evaluated their prognostic significance. METHODS: Cardiac amyloidosis patients with baseline and follow-up echocardiograms were included. Right and left heart function measured at baseline, 1 year, and most recent follow-up were compared and correlated with all-cause mortality or cardiovascular hospitalization. RESULTS: Ninety-three patients were included; 36 (39%) with light chain amyloidosis and 57 (61%) with transthyretin amyloidosis. Among measures of right heart function for the study population and light chain and transthyretin amyloidosis subtypes, only absolute right ventricular (RV) free wall longitudinal strain (FWLS) changed significantly from baseline to 1 year and most recent follow-up echocardiogram. After a median of 26 months (range, 14-35 months), 21 (22%) patients died and 17 (18%) had a cardiovascular hospitalization. Baseline RV FWLS was significantly associated with the primary endpoint (hazard ratio, 1.2 per % change; 95% confidence interval, 0.8-2.6; P < 0.01), whereas change from baseline to 1 year was not for any measure of right heart function. Baseline left ventricular (LV) global longitudinal strain (GLS) and 1 year change were significantly associated with the primary end point. Change in RV FWLS at 1 year was significantly correlated with baseline LV GLS (r = 0.68; P = 0.01) and change at 1 year follow-up (r = 0.72; P < 0.01). CONCLUSIONS: In cardiac amyloidosis patients, baseline RV FWLS was associated with adverse outcomes whereas changes at follow-up was not. Change in RV FWLS was significantly correlated with baseline and follow-up change in LV GLS, possibly reflecting progressive biventricular amyloid deposition.

Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis.

BACKGROUND: The tolerability and utility of combination doxycycline and ursodeoxycholic acid (ursodiol) amyloid fibril disruption therapy for transthyretin cardiac amyloidosis (ATTR CA) in clinical practice is poorly described. METHODS AND RESULTS: We report the clinical experience of 53 ATTR CA patients treated with doxycycline and ursodiol. Six patients (11%) did not tolerate the therapy owing to dermatologic and gastrointestinal effects. Of those remaining, the median follow-up was 22 months (range 8-30), mean age was 71 ± 11years, 41 (87%) were male, and 42 (89%) had wild-type and 5 (11%) mutant ATTR. Five patients (11%) died during follow-up. There was no significant change in New York Heart Association (NYHA) functional class, cardiac biomarkers, or echocardiographic parameters during follow-up. Left ventricular (LV) global longitudinal systolic strain (GLS) improved in 16 patients (38%) (-12 ± 4% to -17 ± 4%; P < .01). Patients whose LV GLS improved were significantly younger and had lower NYHA functional class, troponin-T, N-terminal pro-B-type natriuretic peptide (BNP), and baseline LV GLS levels compared with those whose LV GLS did not improve. Troponin-T improved in follow-up for patients whose LV GLS improved (35 ± 21 to 20 ± 14 ng/L; P = .06). CONCLUSIONS: Doxycycline and ursodiol therapy for treatment of ATTR CA was tolerable and was associated with stabilized markers of disease progression. LV GLS improved in patients with less advanced disease.

3D myocardial deformation analysis from cine MRI as a marker of amyloid protein burden in cardiac amyloidosis: validation versus T1 mapping.

Cardiac amyloidosis (CA) is a significant contributor to heart failure with preserved ejection fraction and is appreciating expanding therapeutic options. Non-invasive tools aimed at accurate identification and surveillance of therapeutic response are of immediate and expanding need. While native and post-contrast T1 mapping quantify expansion of the extra-cellular compartment from amyloid protein deposition, 3D strain analysis of non-contrast cine images offers unique advantages relevant to high prevalence of renal insufficiency in this population and reduced dependency on field strength, pulse sequence, and vendor implementation. We aimed to evaluate global and segmental associations between 3D strain and T1 mapping in patients with cardiac amyloidosis. Twenty consecutive patients with confirmed CA were recruited and underwent a standardized cardiovascular magnetic resonance imaging protocol at 3 T including using multi-planar cine imaging and T1 mapping using a shortened modified look-locker inversion recovery sequence. T1 mapping was performed pre- and (when permitted by renal function) post-contrast and measured for segmental T1 values. Spatially-matched 3D strain-based measures were similarly calculated. Mean left ventricular ejection fraction was 61 ± 21% (range 30-73%). Mean global native T1 was 1308 ± 96 ms. Post-contrast T1 and partition coefficient were 558 ± 104 ms and 0.85 ± 0.31, respectively. Global myocardial strain values were 8.1 ± 2.9% in the longitudinal direction, - 9.2 ± 3.4% in the circumferential direction, and 41.7 ± 22.8% in the maximum principal direction. Segmental analyses confirmed relative worsening in T1 values and reductions in strain values in the basal myocardial segments with relative sparing of the apical segments. Significant associations between T1 and strain-based measures were observed globally and segmentally, with the strongest associations found both globally and segmentally in the circumferential and minimum principal directions of deformation. This study identifies strong associations between 3D myocardial strain and T1-mapping based markers of regional amyloid protein deposition. These findings support expanded investigation of myocardial strain as a surrogate marker of response to novel therapeutic strategies in patients with cardiac amyloidosis.

Comparison of Cardiac Magnetic Resonance Imaging and Echocardiography in Assessment of Left Ventricular Hypertrophy in Fabry Disease.

BACKGROUND: Cardiac hypertrophy in Fabry disease can be assessed using the left ventricular mass index (LVMI) with either echocardiography (LVMI-ECHO) or magnetic resonance imaging (LVMI-CMR). METHODS: A retrospective case series of patients with Fabry disease in Alberta involved a cross-sectional analysis of 32 patients and a longitudinal analysis of 14 of these patients with at least 4 serial CMR measurements. RESULTS: The cross-sectional analysis showed the mean LVMI-ECHO was 97.8 ± 26.0 g/m2, which was higher compared with LVMI-CMR at 81.1 ± 26.9 g/m2 with a mean bias of 16.7 g/m2 (P < 0.001). In the longitudinal analysis, LVMI-ECHO was higher, with an estimated marginal mean of 96.21 ± 6.13 (mean ± standard error of the mean [SEM]) compared with 71.18 ± 5.99 for LVMI-CMR (P < 0.01; generalized estimating equations). There was an association between an increase in LVMI-CMR over time with the presence of cardiac fibrosis, and patients treated with enzyme replacement therapy (ERT) had slower increases than those without therapy. LVMI-ECHO failed to detect these associations owing to the higher variability and tendency to overestimate the LVMI. CONCLUSIONS: We propose the preferred method for measuring LVMI is CMR in patients with Fabry disease.

Recent Advances in Cardiovascular Imaging Relevant to the Management of Patients with Suspected Cardiac Amyloidosis.

Cardiac amyloidosis is a form of infiltrative cardiomyopathy typically presenting with progressive heart failure. The clinical presentation and morphological findings often overlap with other cardiovascular diseases, and frequently results in misdiagnosis and consequent under-reporting. Cardiovascular imaging is playing an increasingly important diagnostic and prognostic role in this referral population, and is reducing the reliance on endomyocardial biopsy as a confirmatory testing. Advancements across multiple cardiac imaging modalities, including echocardiography, magnetic resonance imaging, nuclear imaging, and computed tomography, are improving diagnostic accuracy and offering novel approaches to sub-type differentiation and prognostication. This review explores recent advancements in cardiac imaging for the diagnosis, typing, and staging of cardiac amyloidosis, with a focus on new and evolving techniques. Emphasis is also placed on the promise of non-invasive cardiac imaging to provide value across the spectrum of this clinical disease, from early disease identification (prior to the development of increased wall thickness) through to markers of advanced disease associated with early mortality.

Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence.

BACKGROUND: Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown. METHODS AND RESULTS: Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC-. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC- patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions. CONCLUSIONS: Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias.

Ultrasound guidance for beating heart mitral valve repair augmented by synthetic dynamic CT.

Minimally invasive valvular intervention commonly requires intra-procedural navigation to provide spatial and temporal information of relevant cardiac structures and device components. Recently intra-procedural trans-esophageal echocardiography (TEE) has been exploited for this purpose due to its accessibility, low cost, ease of use, and real-time imaging capacity. However, the position and orientation of tissue targets relative to surgical tools can be challenging to perceive, particularly using 2D imaging planes. In this paper, we propose the use of CT images to provide a high-quality 3D context to enhance ultrasound images through image registration, providing an augmented guidance system with minimal impact on standard clinical workflow. We also describe an approach to generate synthetic 4D CT images through non-rigid registration of available ultrasound. This can be employed to avoid a requirement for higher radiation. Synthetic CT images were validated through direct comparison of synthetic and real multi-phase CT images. Validation of CT and ultrasound image registration was performed for both dynamic and synthetic CT image datasets. Our results demonstrated that the synthetically generated dynamic CT images provide similar anatomical representation for relevant cardiac anatomy relative to real dynamic CT images, and similar high registration accuracy that can be achieved for intra-procedural TEE to this versus real dynamic CT images.

Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

UNLABELLED: Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised. METHODS: Nine adult dogs underwent left anterior descending coronary occlusion with or without reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate the distribution of gadolinium-DTPA (which represents its partition coefficient in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and (99)Tc were determined in a well counter. Linear regression analysis evaluated the relationships between the concentrations of (111)In and (18)F and the dependence of the ratio of (111)In/(18)F to the apparent distribution volume of (99m)Tc-DTPA. RESULTS: In 7 of 9 animals, (111)In increased as (18)F increased with the other 2 animals, showing weak negative slopes. With respect to the dependence of (111)In/(18)F with partition coefficient, 4 animals showed no dependence and 4 showed a weak positive slope, with 1 animal showing a negative slope. Further, in regions of extensive microvascular obstruction, (18)F significantly underestimated the extent of the presence of (111)In. CONCLUSION: In the early post-myocardial infarction period, (18)F-FDG PET imaging after a single bolus administration may underestimate the extent and degree of inflammation within regions of microvascular obstruction.

Model-based navigation of left and right ventricular leads to optimal targets for cardiac resynchronization therapy: a single-center feasibility study.

BACKGROUND: Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. METHODS AND RESULTS: Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66 ± 8 years and 26 ± 8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥ 15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥ 30%). LV ejection fraction improved at 6 months (31 ± 8 versus 26 ± 8%, P=0.04). CONCLUSIONS: This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.

CMR imaging with rapid visual T1 assessment predicts mortality in patients suspected of cardiac amyloidosis.

OBJECTIVES: This study tested the diagnostic and prognostic utility of a rapid, visual T1 assessment method for identification of cardiac amyloidosis (CA) in a "real-life" referral population undergoing cardiac magnetic resonance for suspected CA. BACKGROUND: In patients with confirmed CA, delayed-enhancement cardiac magnetic resonance (DE-CMR) frequently shows a diffuse, global hyperenhancement (HE) pattern. However, imaging is often technically challenging, and the prognostic significance of diffuse HE is unclear. METHODS: Ninety consecutive patients referred for suspected CA and 64 hypertensive patients with left ventricular hypertrophy (LVH) were prospectively enrolled and underwent a modified DE-CMR protocol. After gadolinium administration a method for rapid, visual T1 assessment was used to identify the presence of diffuse HE during the scan, allowing immediate optimization of settings for the conventional DE-CMR that followed. The primary endpoint was all-cause mortality. RESULTS: Among patients with suspected CA, 66% (59 of 90) demonstrated HE, with 81% (48 of 59) of these meeting pre-specified visual T1 assessment criteria for diffuse HE. Among hypertensive LVH patients, 6% (4 of 64) had HE, with none having diffuse HE. During 29 months of follow-up (interquartile range: 12 to 44 months), there were 50 (56%) deaths in patients with suspected CA and 4 (6%) in patients with hypertensive LVH. Multivariable analysis demonstrated that the presence of diffuse HE was the most important predictor of death in the group with suspected CA (hazard ratio: 5.5, 95% confidence interval: 2.7 to 11.0; p < 0.0001) and in the population as a whole (hazard ratio: 6.0, 95% confidence interval 3.0 to 12.1; p < 0.0001). Among 25 patients with myocardial histology obtained during follow-up, the sensitivity, specificity, and accuracy of diffuse HE in the diagnosis of CA were 93%, 70%, and 84%, respectively. CONCLUSIONS: Among patients suspected of CA, the presence of diffuse HE by visual T1 assessment accurately identifies patients with histologically-proven CA and is a strong predictor of mortality.