A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSION: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Total-Body PET/CT Applications in Cardiovascular Diseases: A Perspective Document of the SNMMI Cardiovascular Council.

Digital PET/CT systems with a long axial field of view have become available and are emerging as the current state of the art. These new camera systems provide wider anatomic coverage, leading to major increases in system sensitivity. Preliminary results have demonstrated improvements in image quality and quantification, as well as substantial advantages in tracer kinetic modeling from dynamic imaging. These systems also potentially allow for low-dose examinations and major reductions in acquisition time. Thereby, they hold great promise to improve PET-based interrogation of cardiac physiology and biology. Additionally, the whole-body coverage enables simultaneous assessment of multiple organs and the large vascular structures of the body, opening new opportunities for imaging systemic mechanisms, disorders, or treatments and their interactions with the cardiovascular system as a whole. The aim of this perspective document is to debate the potential applications, challenges, opportunities, and remaining challenges of applying PET/CT with a long axial field of view to the field of cardiovascular disease.

Spatial-temporal V-Net for automatic segmentation and quantification of right ventricle on gated myocardial perfusion SPECT images.

BACKGROUND: Functional assessment of right ventricle (RV) using gated myocardial perfusion single-photon emission computed tomography (MPS) heavily relies on the precise extraction of right ventricular contours. PURPOSE: In this paper, we present a new deep-learning-based model integrating both the spatial and temporal features in gated MPS images to perform the segmentation of the RV epicardium and endocardium. METHODS: By integrating the spatial features from each cardiac frame of the gated MPS and the temporal features from the sequential cardiac frames of the gated MPS, we developed a Spatial-Temporal V-Net (ST-VNet) for automatic extraction of RV endocardial and epicardial contours. In the ST-VNet, a V-Net is employed to hierarchically extract spatial features, and convolutional long-term short-term memory (ConvLSTM) units are added to the skip-connection pathway to extract the temporal features. The input of the ST-VNet is ECG-gated sequential frames of the MPS images and the output is the probability map of the epicardial or endocardial masks. A Dice similarity coefficient (DSC) loss which penalizes the discrepancy between the model prediction and the manual annotation was adopted to optimize the segmentation model. RESULTS: Our segmentation model was trained and validated on a retrospective dataset with 45 subjects, and the cardiac cycle of each subject was divided into eight gates. The proposed ST-VNet achieved a DSC of 0.8914 and 0.8157 for the RV epicardium and endocardium segmentation, respectively. The mean absolute error, the mean squared error, and the Pearson correlation coefficient of the RV ejection fraction (RVEF) between the manual annotation and the model prediction were 0.0609, 0.0830, and 0.6985. CONCLUSION: Our proposed ST-VNet is an effective model for RV segmentation. It has great promise for clinical use in RV functional assessment.

Clinical Application of 99mTc-Pyrophosphate Scintigraphy for Diagnosis of Cardiac Amyloidosis: A Case Series.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of insoluble amyloid protein in the myocardial interstitium. The accumulation of amyloid protein causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Two primary types of amyloidosis-transthyretin and immunoglobulin light chain-account for nearly 95% of all CA diagnoses. Three case studies are presented. The first demonstrates a patient positive for transthyretin amyloidosis, the second demonstrates a patient positive for light-chain CA, and the third demonstrates a patient showing blood-pool uptake on the [99mTc]Tc-pyrophosphate scan but negative for CA.

Chronological comparison of TAVI and SAVR stratified to surgical risk: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been established as a reasonable alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis. However, long-term outcomes including valve durability and the need for reintervention are unanswered, especially in younger patients who tend to be low surgical risk. We performed a meta-analysis comparing clinical outcomes after TAVI and SAVR over 5 years stratified to low, intermediate, and high surgical risks. METHODS: We identified propensity score-matched observational studies and randomised controlled trials comparing TAVI and SAVR. Primary outcomes, including all-cause mortality, moderate or severe aortic regurgitation, moderate or severe paravalvular regurgitation, pacemaker placement, and stroke, were extracted. Meta-analyses of outcomes after TAVI compared to SAVR were conducted for different periods of follow-up. Meta-regression was also performed to analyse the correlation of outcomes over time. RESULTS: A total of 36 studies consisting of 7 RCTs and 29 propensity score-matched studies were selected. TAVI was associated with higher all-cause mortality at 4-5 years in patients with low or intermediate surgical risk. Meta-regression time demonstrated an increasing trend in the risk of all-cause mortality after TAVI compared with SAVR. TAVI was generally associated with a higher risk of moderate or severe aortic regurgitation, moderate or severe paravalvular regurgitation, and pacemaker placement. CONCLUSIONS: TAVI demonstrated an increasing trend of all-cause mortality compared with SAVR when evaluated over a long-term follow-up. More long-term data from recent studies using newer-generation valves and state-of-the-art techniques are needed to accurately assign risks.

Transcatheter aortic valve implantation (TAVI) was associated with increased all-cause mortality at longer periods of follow-up irrespective of surgical risk. Aortic regurgitation, paravalvular regurgitation, major vascular complications, and pacemaker placement favoured surgical aortic valve replacement (SAVR) over TAVI. TAVI remained superior to SAVR in major bleeding and renal failure events. Long-term data on newer generation valves and up-to-date implantation techniques may provide better durability and improved outcomes after TAVI.

Novel Tracers for the Imaging of Cardiac Amyloidosis.

Radionuclide scintigraphy with technetium-labeled bisphosphonates has brought a paradigm shift in diagnosing cardiac amyloidosis (CA), with transthyretin CA now being effectively diagnosed without the need for tissue biopsy. Yet, deficits remain, such as methods for the noninvasive diagnosis of light-chain CA, means to detect CA early, prognostication, monitoring, and therapy response assessment. To address these issues, there has been growing interest in the development and implementation of amyloid-specific radiotracers for PET. The aim of this review is to educate the reader on these novel imaging tracers. Though still investigational, these novel tracers-given their many advantages-are clearly the future of nuclear imaging in CA.

Comparison of cardio-focal and chest reconstruction of technetium-99m pyrophosphate scintigraphy for diagnosis of transthyretin cardiac amyloidosis: a quality assurance study.

BACKGROUND: SPECT improves diagnostic specificity of Technetium-99m pyrophosphate (PYP) scintigraphy. Diagnostic performance of PYP data, reconstructed as either chest or cardio-focal SPECT is not known. METHODS: In this quality assurance study, blinded evaluation of PYP SPECT/CT data from 102 Caucasian patients (mean age 76 ± 11 years, 67% men) was performed by two readers. Reader 1 reviewed planar and PYP chest SPECT, while reader 2 reviewed planar and cardio-focal PYP SPECT. Demographic, clinical, and other testing data were obtained from the electronic medical records. RESULTS: A total of 41 patients (40%) were considered positive based on myocardial uptake on chest PYP SPECT. Of these, 98% of the patients had a Perugini score ≥ 2 on planar imaging. There was good agreement between the two readers for visual score ≥ 2 (k = .88, P < .001) and excellent agreement for myocardial uptake on tomographic imaging (98%, P < .001). Only one study was categorized as false negative by cardio-focal SPECT reconstruction. Non-diffuse myocardial uptake was identified in 22% of those with a positive PYP SPECT. CONCLUSION: When read by experienced readers, chest and cardio-focal reconstruction of PYP SPECT have comparable diagnostic performance. A substantial proportion of patients with a positive PYP SPECT have a non-diffuse distribution of PYP. Given the possibility of misclassification of non-diffuse myocardial uptake on cardio-focal reconstruction alone, chest reconstruction of PYP scintigraphy should be strongly considered.

Automatic reorientation by deep learning to generate short-axis SPECT myocardial perfusion images.

BACKGROUND: Single photon emission computed tomography (SPECT) myocardial perfusion images (MPI) can be displayed both in traditional short-axis (SA) cardiac planes and polar maps for interpretation and quantification. It is essential to reorient the reconstructed transaxial SPECT MPI into standard SA slices. This study is aimed to develop a deep-learning-based approach for automatic reorientation of MPI. METHODS: A total of 254 patients were enrolled, including 226 stress SPECT MPIs and 247 rest SPECT MPIs. Fivefold cross-validation with 180 stress and 201 rest MPIs was used for training and internal validation; the remaining images were used for testing. The rigid transformation parameters (translation and rotation) from manual reorientation were annotated by an experienced nuclear cardiologist and used as the reference standard. A convolutional neural network (CNN) was designed to predict the transformation parameters. Then, the derived transform was applied to the grid generator and sampler in spatial transformer network (STN) to generate the reoriented image. A loss function containing mean absolute errors for translation and mean square errors for rotation was employed. A three-stage optimization strategy was adopted for model optimization: (1) optimize the translation parameters while fixing the rotation parameters; (2) optimize rotation parameters while fixing the translation parameters; (3) optimize both translation and rotation parameters together. RESULTS: In the test set, the Spearman determination coefficients of the translation distances and rotation angles between the model prediction and the reference standard were 0.993 in X axis, 0.992 in Y axis, 0.994 in Z axis, 0.987 along X axis, 0.990 along Y axis and 0.996 along Z axis, respectively. For the 46 stress MPIs in the test set, the Spearman determination coefficients were 0.858 in percentage of profusion defect (PPD) and 0.858 in summed stress score (SSS); for the 46 rest MPIs in the test set, the Spearman determination coefficients were 0.9 in PPD and 0.9 in summed rest score (SRS). CONCLUSIONS: Our deep learning-based LV reorientation method is able to accurately generate the SA images. Technical validations and subsequent evaluations of measured clinical parameters show that it has great promise for clinical use.

Echocardiographic indices of left ventricular function and filling pressure are not related to blood pool activity on pyrophosphate scintigraphy.

BACKGROUND: Pyrophosphate (PYP) imaging has a high diagnostic accuracy for transthyretin cardiac amyloidosis (ATTR-CA). Indeterminate findings are often reported due to persistent blood pool activity, presumed to be from low cardiac output. We evaluated the relationship between blood pool activity on PYP imaging and echocardiographic indices of cardiac function. METHODS: Clinical and imaging data of 189 patients referred for PYP scintigraphy were evaluated. All patients underwent planar imaging and SPECT (diagnostic standard). Among those with a negative PYP SPECT, persistent left ventricular blood pool activity on planar images was inferred by a visual score ≥2 or a heart-to-contralateral (HCL) ratio ≥ 1.5. Absence of blood pool activity was inferred when both visual score was < 2 and HCL was < 1.5. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), stroke volume index (SVi), and left atrial pressure (LAP) were calculated from standard transthoracic echocardiograms. RESULTS: ATTR-CA was present in 43 (23%) patients. Among those with a negative PYP SPECT, 11 patients had significant blood pool activity. Patients with ATTR-CA had a lower LVEF, SVi, and GLS, with a higher LAP, compared to those without ATTR-CA. Among those without ATTR-CA, there were no significant differences in these parameters. CONCLUSION: Approximately 8% of patients with a negative PYP SPECT have significant blood pool activity. Measures of cardiac function are not different among those with and without blood pool activity. PYP SPECT should be routinely performed in all patients to avoid false image interpretation.

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response.

BACKGROUND: Studies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. METHODS: One hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 [Formula: see text] 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. RESULTS: Complete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. CONCLUSIONS: AE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Multimodality imaging for diagnosis of subclinical hereditary transthyretin cardiac amyloidosis.

We present a case of a patient with worsening visual acuity and dense vitreal debris who was found to have vitreal transthyretin amyloid (ATTR) infiltration. Cardiac workup, performed to identify systemic amyloidosis, demonstrated focal myocardial amyloid infiltration on pyrophosphate (PYP) scintigraphy and cardiac magnetic resonance (CMR), resulting in a diagnosis of subclinical ATTR cardiac amyloidosis (ATTR-CA). Patient was identified as a carrier of p.S70R mutation which results in an aggressive ATTR phenotype. Patient is tolerating transthyretin silencer therapy well. Through this case, we discuss the role of a multimodality imaging approach for the diagnosis of subclinical ATTR-CA.

Network Meta-Analysis Comparing Angiotensin Receptor-Neprilysin Inhibitors, Angiotensin Receptor Blockers, and Angiotensin-Converting Enzyme Inhibitors in Heart Failure With Reduced Ejection Fraction.

The superiority of angiotensin receptor-neprilysin inhibitor (ARNI) over angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) has not been reassessed after the publication of recent trials that did not find clinical benefits. Therefore, we performed an updated network meta-analysis comparing the efficacy and safety of ARNI, ACE-I, ARB, and placebo in heart failure with reduced ejection fraction. We included randomized clinical trials that compared ARNI, ARB, ACE-I, and placebo in heart failure with reduced ejection fraction. We extracted prespecified efficacy end points and produced network estimates, p scores, and surface under the cumulative ranking curve scores using frequentist and Bayesian network meta-analysis approaches. A total of 28 randomized controlled trials including 47,407 patients were included. ARNI was associated with lower risk of all-cause mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68 to 0.96), cardiac death (RR 0.79, 95% CI 0.64 to 0.99), and major adverse cardiac events (MACEs; RR 0.83, 95% CI 0.72 to 0.97) but higher risk of hypotension (RR 1.46, 95% CI 1.02 to 2.10) than ARB. ARNI was associated with lower risk of MACE (RR 0.85, 95% CI 0.74 to 0.97), but higher risk of hypotension (RR 1.69, 95% CI 1.27 to 2.24) compared with ACE-I. P scores and surface under the cumulative ranking curve scores demonstrated superiority of ARNI over ARB and ACE-I in all-cause mortality, cardiac death, MACE, and hospitalization for heart failure. In conclusion, ARNI was associated with improved clinical outcomes, except for higher risk of hypotension, compared with ARB and ACE-I.