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.

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.

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.

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.

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.

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.

Coexistent transthyretin amyloid cardiomyopathy and monoclonal gammopathy: Diagnostic challenges and prognostic implications.

Establishing an accurate diagnosis of amyloid subtype in patients with coexistent cardiac amyloidosis and monoclonal gammopathy is crucial due to treatment and prognostic implications. Here, we discuss a case of coexistent diagnoses of transthyretin amyloid cardiomyopathy and smoldering multiple myeloma, highlighting the challenges associated with the possibility of several disease combinations and the limitations of diagnostic testing. In addition, the importance of clinical clues such as disease course and progression, patient preference, and multidisciplinary collaboration should not be discounted in the diagnostic and management approach of these patients.

Abnormal vasodilator stress electrocardiogram with normal myocardial perfusion: Clinical decision-making and review of literature.

Ischemic electrocardiographic (ECG) changes during vasodilator stress testing in the presence of abnormal myocardial perfusion imaging (MPI) are associated with more severe coronary artery disease (CAD). However, significance of ECG changes during vasodilator stress test with normal MPI has been controversial. Here, we discuss two cases of significant ischemic ECG changes with vasodilator stress and normal MPI, whose subsequent workup revealed severe obstructive CAD. We also review the available literature on the occurrence and mechanism of these discrepant findings and propose recommendations for management.

Three-dimensional Fusion of Myocardial Perfusion SPECT and Invasive Coronary Angiography Guides Coronary Revascularization.

BACKGROUND: SPECT myocardial perfusion imaging (SPECT MPI) and invasive coronary angiography (ICA) provide complementary clinical information in the diagnosis of coronary artery disease (CAD). We have developed an approach for 3D fusion of perfusion data from SPECT MPI and coronary anatomy from ICA. In this study, we aimed to evaluate its clinical value when compared to the traditional side-by-side readings. METHODS: Thirty-six CAD patients who had at least one stenosis ≥ 50% were retrospectively enrolled. Based on the presence of a perfusion defect in a territory subtended by a coronary vessel, all vessels were classified as matched, unmatched, or normal groups via both the fusion and side-by-side analysis. The treatments recommended by the fusion and side-by-side analysis were compared with those that the patients received. Major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization, were assessed. RESULTS: The overall vessel-based concordance was 78.7% between the fusion and side-by-side analysis. Compared with the side-by-side analysis, 23 coronary arteries (29 equivocal segments) of 19 patients were reclassified via fusion of data. In the matched, unmatched, and normal groups, the numbers of vessels with hemodynamically significant stenosis which caused reversible defect were 37 vs 53, 28 vs 14, and 43 vs 41 (P < .01) when comparing the side-by-side analysis with the fusion, and the revascularization ratios per vessel were 69% vs 88%, 29% vs 10%, and 2% vs 2% between them. During the five-year follow-up, 8 patients (22.2%) experienced MACE. Patients who received the same treatment as the guidance of 3D fusion results (n = 22) had superior outcomes when compared with those who did not (n = 14) (P < .01). CONCLUSIONS: Compared with the side-by-side analysis, the 3D fusion of SPECT MPI and ICA provided incremental diagnostic and prognostic value.

Asystole following Regadenoson administration: Review of literature, risk factors and management.

Regadenoson, a selective A2A receptor agonist, is widely used for vasodilator stress myocardial perfusion imaging and has a superior adverse effect profile when compared with other agents. However, with widespread use, there have been several reported cases of Regadenoson induced bradyarrhythmias and even asystole in patients with no known conduction system disease. In this article, we report a case of asystole following Regadenoson administration, evaluate mechanisms and risk factors for Regadenoson induced bradyarrhythmias to better identify patients at risk. We also review the available treatment options and propose recommendations for limiting its risk.

Patient first versus computed tomography first strategy in testing for stable coronary artery disease: dispelling the prevailing myths and biases.

We advocate an evidence-based discussion for a patient first philosophy when considering "the right test for the right patient." Numerous test options exist for the evaluation of symptoms of possible stable ischemic heart disease. Major guidelines have traditionally focused on functional testing with or without imaging to clarify symptoms, diagnose ischemia, stratify prognosis, and guide management. Recently, industry advocates have emphasized modality-specific approaches such as computed tomography (CT First) as an initial test strategy for possible stable CAD. We review the key evidence to demonstrate that current best practice would focus on a patient first approach rather than a modality-specific approach.

Comparison of planar with tomographic pyrophosphate scintigraphy for transthyretin cardiac amyloidosis: Perils and pitfalls.

BACKGROUND: Tc-99m pyrophosphate (PYP) SPECT is recommended for indeterminate findings on planar imaging. We aimed to compare the findings on planar PYP scintigraphy alone to that of routinely performed PYP SPECT. METHODS: PYP scintigraphy data of 133 patients (53% men; mean age 76 years) were evaluated. SPECT was routinely performed following 1-hour planar imaging, in all cases. Semiquantitative visual score and heart-to-contralateral (H/CL) ratio were determined in all patients as recommended. RESULTS: PYP images from 35 patients (26%) were considered to be positive based on SPECT myocardial uptake. Among them, 20 (57%) had a H/CL ratio ≥1.5 and 34 had a visual score ≥ 2. SPECT identified myocardial uptake in one patient with a visual score < 2 and refuted the presence of myocardial uptake in two patients with a visual score ≥ 2. Visual score correlated well with SPECT (r = 0.94; P < .0001) and had an accuracy of 98% for tomographic myocardial uptake. Addition of H/CL ratio reduced the diagnostic performance of visual score. CONCLUSIONS: Planar-derived visual score has an excellent accuracy for tomographic myocardial uptake, though it misclassifies a small proportion of patients. H/CL ratio decreases the diagnostic certainty of planar imaging. Tomographic imaging prevents misdiagnoses and should always be performed.

Coronary artery disease in patients with human immunodeficiency virus infection.

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.

The role of cardiac imaging in the management of non-ischemic cardiovascular diseases in human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) has become the pandemic of the new century. About 36.9 million people are living with HIV worldwide. The introduction of antiretroviral therapy in 1996 has dramatically changed the global landscape of HIV care, resulting in significantly improved survival and changing HIV to a chronic disease. With near-normal life expectancy, contemporary cardiac care faces multiple challenges of cardiovascular diseases, disorders specific to HIV/AIDS, and those related to aging and higher prevalence of traditional risk factors. Non-ischemic cardiovascular diseases are major components of cardiovascular morbidity and mortality in HIV/AIDS. Non-invasive cardiac imaging plays a pivotal role in the management of these diseases. This review summarizes the non-ischemic presentation of the HIV cardiovascular spectrum focusing on the role of cardiac imaging in the management of these disorders.

Assessment of myocardial viability using single-photon emission computed tomography myocardial perfusion imaging.

PURPOSE OF REVIEW: The assessment of myocardial viability continues to be a pressing and sometimes challenging clinical question. Among other imaging modalities proven to be useful in the assessment of myocardial viability, single-photon emission computed tomography (SPECT) instrumentation and expertise continue to be the most widely available to the practicing physicians. Understanding the utility of SPECT myocardial perfusion imaging in this domain is an enduring need. RECENT FINDINGS: A wealth of basic science and clinical data established the value of a variety of Tl-201 and Tc-99m SPECT protocols in the assessment of myocardial viability. The diagnostic performance for Tl-201 and Tc-99m imaging protocols for identifying viable myocardium is very good and is comparable for both agents. Quantitative assessment of radiotracer uptake can predict, in an objective manner, the probability of recovery of myocardial function following revascularization. SUMMARY: SPECT myocardial perfusion imaging with Tl-201 and Tc-99m tracers can provide an objective and quantifiable assessment of myocardial viability, which can help predict the likelihood of myocardial function recovery following coronary revascularization. Effective application of this imaging technique can guide clinical decision-making for coronary revascularization.

The association of imaging equipment age with other quality metrics and successful laboratory accreditation by the Intersocietal Accreditation Commission.

BACKGROUND: Intersocietal Accreditation Commission (IAC) accreditation is granted or delayed depending on the fulfillment of several quality metrics. Investing in up-to-date equipment might reflect a commitment to quality. METHODS: Data from echocardiography (n = 3079) and nuclear cardiology (n = 1835) accreditation applications submitted between 2012 and 2014 were evaluated to determine the mean age of laboratory equipment. Laboratory quality was assessed by the number of missing quality metrics, and a composite quality score was calculated as the sum of missing quality metrics. A lower score thus represented better laboratory quality. The relationship between equipment age and quality was explored as an interaction term between equipment age and the composite quality score and was incorporated into regression models for prediction of accreditation status. RESULTS: During the study period, 49% of echocardiography and 42% of nuclear laboratories were granted accreditation without delay. For both echocardiography and nuclear laboratories, there was a statistically significant trend toward an increasing number of missing quality metrics with increasing quartiles of equipment age. The interaction between equipment age and the composite quality score was a significant predictor of delay of accreditation for both echocardiography and nuclear cardiology laboratories, with a stronger association for 1st-time applicants. Among sites applying for accreditation in both modalities simultaneously, accreditation in one modality predicted the accreditation decision for the other. CONCLUSIONS: Laboratory quality is an important determinant of IAC accreditation, and equipment age is an effect modifier of this relationship. Contemporary equipment likely reflects a commitment to quality, for both echocardiography and nuclear laboratories.

Diagnosis and Prognosis of Coronary Artery Disease with SPECT and PET.

PURPOSE OF REVIEW: Radionuclide myocardial perfusion imaging (MPI) continues to be the most reliable modality for diagnosis of hemodynamically significant coronary artery disease (CAD). The application of radionuclide MPI using single photon emission computed tomography (SEPCT) and positron emission tomography (PET) for CAD is reviewed, with emphasis on diagnosis and risk stratification. RECENT FINDINGS: Contemporary studies have reported the diagnostic and prognostic value of novel imaging protocols, employing stress-first or stress-only approach. In addition, the superior diagnostic value of PET has been established with a role of assessment of myocardial blood flow to improve risk stratification. The utility of MPI in special populations, such as the elderly, women, and diabetic patients has also been recently evaluated. Furthermore, multicenter studies have reported a similar diagnostic and prognostic value of radionuclide MPI compared with other functional and anatomical techniques for CAD. Radionuclide MPI with SPECT and PET are efficacious for diagnosis and prognosis of CAD. Its universal application in varied patient populations highlights its excellent clinical effectiveness.

Carotid Artery Wall Thickness and Incident Cardiovascular Events: A Comparison between US and MRI in the Multi-Ethnic Study of Atherosclerosis (MESA).

Purpose To compare common carotid artery (CCA) wall thickness measured manually by using US and semiautomatically by using MRI, and to examine their associations with incident coronary heart disease and stroke. Materials and Methods This prospective study enrolled 698 participants without a history of clinical cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis (MESA) from July 2000 to December 2013 (mean age, 63 years; range, 45 to 84 years; same for men and women). All participants provided written informed consent. CCA wall thickness was measured with US as well as both noncontrast proton-density-weighted and intravenous gadolinium-enhanced MRI. Cox proportional hazards models were used to assess the associations between wall thickness measurements by using US and MRI with CVD outcomes. Results The adjusted hazard ratios for coronary heart disease, stroke, and CVD associated with per standard deviation increase in intima-media thickness were 1.10, 1.08, and 1.14, respectively. The corresponding associations for mean wall thickness measured with proton-density-weighted MRI were 1.32, 1.48, and 1.37, and for mean wall thickness measured with gadolinium-enhanced MRI were 1.27, 1.58, and 1.38. When included simultaneously in the same model, MRI wall thickness, but not intima-media thickness, remained associated with outcomes. Conclusion For individuals without known cardiovascular disease at baseline, wall thickness measurements by using MRI were more consistently associated with incident cardiovascular disease, particularly stroke, than were intima-media thickness by using US. © RSNA, 2018 Online supplemental material is available for this article.