Cardiovascular positron emission tomography: established and emerging role in cardiovascular diseases.

Cardiac positron emission tomography (PET) imaging has established themselves firmly as excellent and reliable functional imaging modalities in assessment of the spectrum of coronary artery disease. With the explosion of technology advances and the dream of flow quantification now a reality, the value of PET is now well realized. Cardiac PET has proved itself as precise imaging modality that provides functional imaging of the heart in addition to anatomical imaging. It has established itself as one of the best available techniques for evaluation of myocardial viability. Hybrid PET/computed tomography provides simultaneous integration of coronary anatomy and function with myocardial perfusion and metabolism, thereby improving characterization of the dysfunctional area and chronic coronary artery disease. The availability of quantitative myocardial blood flow evaluation with PET provides additional prognostic information and increases diagnostic accuracy in the management of patients with coronary artery disease. Hybrid imaging seems to hold immense potential in optimizing management of cardiovascular diseases and furthering clinical research.

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow.

Background and Objectives: Cardiac amyloidosis is a disorder caused by amyloid fibril deposition in the extracellular space of the heart. Almost all forms of clinical cardiac amyloidosis are transthyretin amyloidosis (ATTR) or light chain amyloidosis. 99m technetium pyrophosphate (99mTc PYP scan) has changed the landscape of the non-biopsy diagnosis of ATTR cardiac amyloidosis (ATTR-CA) by providing remarkably high diagnostic accuracy. We examined our experience with PYP scans in patients undergoing workup for ATTR-CA and evaluated the diagnostic workflow in patients with intermediate PYP scan results. Materials and Methods: Retrospective chart review study in which we analyzed data of 84 patients who underwent c-99m pyrophosphate (PYP) SPECT scan for the diagnosis of ATTR-CA from 2017 till 2021 at our institution. We identified three groups: Low uptake (PYPL uptake ratio < 1.2 + visual grade 1/0), n = 30, Intermediate uptake (PYPI uptake ratio 1.2-1.49, visual grade 2/3), n = 25 and High uptake (PYPH uptake ratio ≥ 1.5 + visual grade 2/3), n = 29. We reviewed patients' demographics, medical histories, echo parameters and diagnostic testing including light chain analysis, cardiac magnetic resonance results, and biopsies. Results: Mean patients' age was 73, male-to=female ratio 3:1, 59% of patients were African American. Cardiovascular comorbidities, cardiac biomarkers (BNP and Troponin) and amyloid-related neuropathy were similar in all groups. A statistically significant difference in septal thickness/posterior wall thickness and final diagnosis were found between the groups. The distribution of overall diagnostic testing ratios for the PYPI group included serum protein electrophoresis 92%, urine protein electrophoresis 65%, free light chain 80%, CMR 32%, tissue biopsy done in 20% and BM biopsy in 16%, which are similar to the ratios of other groups. Overall, 25% (n = 5, 4 TTR-CA and 1 AL Amyloid) of patients in the PYPI group had a final diagnosis of CA established with additional testing (p = 0.001 vs. other groups). Conclusions: The 99mPYP scan is an accurate noninvasive test for cardiac ATTR-CA. Importantly, 25% of the PYPI group had a final diagnosis of ATTR-CA reiterating that diagnosis needs to be pursued in PYPI cases based on clinical suspicion. Routine evaluation and exclusion of light chain disease and establishing a consistent workflow for amyloid diagnosis and continued education for technologists and readers of PYP scans is key to a successful amyloidosis workup.

Multimodality imaging approach to cardiac amyloidosis: part 2.

With recent advances in cardiac imaging, genetics, and treatment options, cardiac amyloidosis (CA) is now recognized as an important and under diagnosed condition contributing to cardiovascular morbidity and mortality. Although still considered a rare disease, CA is now recognized as an important contributor to heart failure with preserved ejection fraction (HFPEF) and low gradient aortic stenosis, two important conditions commonly faced in clinical practice. This review uses clinical scenarios to highlight the complementary role of traditional imaging tools such as electrocardiogram (ECG) and echocardiography (echo) in conjunction with advanced cardiac imaging with cardiac magnetic resonance (CMR) and nuclear cardiac scintigraphy using bone avid tracers in the comprehensive workup of CA. We also highlight the importance of workup of light chain disease as part of integration of imaging findings and discuss the key aspects of various imaging modalities. Finally, an algorithm integrating clinical suspicion, laboratory testing, and imaging in the workup of CA is presented.

Epidemiology and clinical manifestations of cardiac amyloidosis.

Cardiac amyloidosis, once considered a rare disease, has garnered significant attention over the last few years due to three key reasons: first, increased recognition of this disease in conjunction with various common cardiac conditions such as heart failure with preserved ejection fraction and aortic stenosis; second, due to the advent of promising new therapies for light chain disease (AL), transthyretin (ATTR) cardiomyopathy, and amyloid neuropathy; finally, the advancements in cardiac imaging including echocardiography, magnetic resonance imaging, and nuclear cardiac scintigraphy aid in non-biopsy diagnosis of ATTR cardiac amyloidosis. The hereditary forms of ATTR have further come into importance with the availability of genetic testing and increased prevalence of certain mutations in African Americans. Recognition of non-cardiac clues to this disease has gained importance and reiterates that high clinical suspicion, detailed patient history, and examination with appropriate use of imaging are vital to confirm the diagnosis.

Healthcare resource utilization among patients receiving non-invasive testing for coronary artery disease in an outpatient setting: A cohort study reflecting daily practice trends.

BACKGROUND: Accurate, early diagnosis and the initiation of appropriate treatment is central to reducing the clinical burden of coronary artery disease (CAD); however, real-world evidence characterizing healthcare resource utilization (HCRU) associated with testing for CAD is lacking. METHODS AND RESULTS: Using a non-interventional, retrospective, secondary database analysis, patients aged ≥18 years who underwent outpatient non-invasive cardiac diagnostic testing were identified. The primary objective was to gain an understanding of pre- and post-assessment care pathways and the associated interventions for patients who underwent non-invasive testing for CAD in either an outpatient or emergency department setting. Overall, chest pain was the primary reason for the index visit (54.8%), followed by shortness of breath (23.7%), myocardial infarction (MI), coronary artery disease (CAD) or congestive heart failure (CHF) (3.8%), and other (46.8%); 3.0% of patients had no apparent reason for testing in the last 45 days. Single-photon emission computed tomography (SPECT) was the dominant diagnostic testing modality (40.3%). During the 90-day follow-up, 7.3% (n = 22,083) of patients were diagnosed with CAD; among these patients, 19.4% had repeat diagnostic testing, 26.0% of patients had a revascularization procedure, and 65.6% underwent cardiac catheterization. These rates varied by testing modality. CONCLUSIONS: In this study of a large real-world data sample, variability in the use of non-invasive tests and HCRU were evident. These results may assist efforts to optimize system-wide care/diagnostic pathways and value-based treatment decisions for patients.

Prognostic usefulness of planar 123I-MIBG scintigraphic images of myocardial sympathetic innervation in congestive heart failure: Follow-Up data from ADMIRE-HF.

BACKGROUND: To evaluate whether planar 123I-MIBG myocardial scintigraphy predicts risk of death in heart failure (HF) patients up to 5 years after imaging. METHODS AND RESULTS: Subjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio (< 1.60 vs ≥ 1.60) on planar 123I-MIBG scintigraphic images obtained at baseline in ADMIRE-HF. Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate time to death, cardiac death, or arrhythmic events for subjects stratified by H/M ratio, baseline left ventricular ejection fraction (LVEF: < 25% and 25 to ≤ 35%), and by H/M strata within LVEF strata. All-cause mortality was 38.4% vs 20.9% and cardiac mortality was 16.8% vs 4.5%, in subjects with H/M < 1.60 vs ≥ 1.60, respectively (P < 0.05 for both comparisons). Subjects with preserved sympathetic innervation of the myocardium (H/M ≥ 1.60) were at significantly lower risk of all-cause and cardiac death, arrhythmic events, sudden cardiac death, or potentially life-threatening arrhythmias. Within LVEF strata, a trend toward a higher mortality for subjects with H/M < 1.60 was observed reaching significance for LVEF 25 to ≤ 35% only. CONCLUSIONS: During a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.

Echocardiographic Changes in the Context of Metal-on-Metal Versus Nonmetal-on-Metal Total Hip Arthroplasty.

BACKGROUND: The purpose of this study is to determine if there is a difference in echocardiographic results between patients with metal-on-metal (MoM) vs non-MoM total hip arthroplasty (THA) and to determine if a correlation exists between serum metal levels and echocardiographic outcomes. METHODS: Seventy-five patients with the same modular THA enrolled in this prospective cohort study, and 49 had MoM bearings. All patients had serum cobalt, chromium, and titanium levels drawn at 2 study visits with a transthoracic echocardiogram at the second visit. Serum metal concentrations and echocardiographic parameters were compared with 2-way t-tests. Multiple linear regression analyses identified any significant predictors of echocardiographic outcomes. RESULTS: Mean serum cobalt and chromium levels were significantly greater in the MoM group at both time-points (P < .001 and P < .05, respectively). Titanium levels were similar between groups (P > .05). MoM patients had significantly lower global longitudinal strain compared with the non-MoM group (18.4% vs 20.2%; P = .026). Serum cobalt concentration was found to be an independent predictor of tricuspid annular plane systolic excursion (P = .02). CONCLUSION: MoM THA bearings are associated with increased serum cobalt and chromium levels. Patients with MoM THAs had decreased global longitudinal strain, a measure of left ventricular function, but both groups remained within normal range. The clinical impact of the positive association between serum cobalt concentration and tricuspid annular plane systolic excursion, a marker of right ventricular function, deserves further study. These findings can reassure physicians and patients that metal-induced cardiomyopathy is not typical in the setting of MoM THA. LEVEL OF EVIDENCE: Level II, Prospective Cohort Study.

Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter test-retest reproducibility study.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test-retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test-retest difference was 0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

The EXERRT trial: "EXErcise to Regadenoson in Recovery Trial": A phase 3b, open-label, parallel group, randomized, multicenter study to assess regadenoson administration following an inadequate exercise stress test as compared to regadenoson without exercise for myocardial perfusion imaging using a SPECT protocol.

BACKGROUND: This study assessed the non-inferiority and safety of regadenoson administration during recovery from inadequate exercise compared with administration without exercise. METHODS: Patients unable to achieve adequate exercise stress were randomized to regadenoson 0.4 mg either during recovery (Ex-Reg) or 1 hour after inadequate exercise (Regadenoson) (MPI1). All patients also underwent non-exercise regadenoson MPI 1-14 days later (MPI2). The number of segments with reversible perfusion defects (RPDs) detected using single photon emission computerized tomography imaging was categorized. The primary analysis evaluated the majority agreement rate between Ex-Reg and Regadenoson groups. RESULTS: 1,147 patients were randomized. The lower bound of the 95% confidence interval of the difference in agreement rates (-6%) was above the -7.5% non-inferiority margin, demonstrating non-inferiority of Ex-Reg to Regadenoson. Adverse events were numerically less with Ex-Reg (MPI1). In the Ex-Reg group, one patient developed an acute coronary syndrome and another had a myocardial infarction following regadenoson after exercise. Upon review, both had electrocardiographic changes consistent with ischemia prior to regadenoson. CONCLUSIONS: Administering regadenoson during recovery from inadequate exercise results in comparable categorization of segments with RPDs and with careful monitoring appears to be well tolerated in patients without signs/symptoms of ischemia during exercise and recovery.

Systemic right ventricle complications in levo-transposition of the great arteries: A case report and review of literature.

BACKGROUND: Congenitally corrected levo-transposition of the great arteries (L-TGA) is a congenital heart disease in which the ventricles and great arteries are transposed from their typical anatomy. In L-TGA, the double discordance, atrioventricular and ventriculoarterial, create an acyanotic milieu which allows patients to survive their early decades, however, progressive systemic right ventricle (sRV) dysfunction creates complications later in life. sRV dysfunction and remodeling predisposes patients to intracardiac thrombus (ICT) formation. CASE SUMMARY: A 40-year-old male with L-TGA presented with symptoms of acute decompensated heart failure. In childhood, he had surgical repair of a ventricular septal defect. In adulthood, he developed sRV dysfunction, systemic tricuspid valve (sTV) regurgitation, and left-bundle branch block for which he underwent cardiac resynchronization therapy. Transthoracic echocardiogram showed a sRV ejection fraction of 40%, severe sTV regurgitation, and a newly identified sRV ICT. ICT was confirmed by ultrasound-enhancing agents and transesophageal echocardiography. Our patient was optimized with guideline-directed medical therapy and diuresis. Anticoagulation was achieved with a vitamin K antagonist (VKA) and he was later referred for evaluation by advanced heart failure and heart transplant services. CONCLUSION: Anticoagulation with VKA is the mainstay of treatment in the absence of conclusive data supporting direct oral anticoagulant use in ICT in patients with congenital heart disease. This case illustrates the natural history of L-TGA and highlights the importance of surveillance and monitoring with dedicated cardiac imaging to identify complications.

Stress electrocardiography testing in coronary artery disease: Is it time for its swan song or to redefine its role in the modern era ?

Stress electrocardiography (sECG) or treadmill stress testing is a well validated noninvasive diagnostic modality available to clinicians at low cost yet providing valuable functional data for coronary artery disease (CAD) diagnostic and prognostic evaluation. With the advances in cardiac imaging in both functional and anatomic fronts and the existing limitations of sECG testing, this modality appears less favored worldwide as reflected in some recent guideline updates. We review the past present and future of sECG to provide a viewpoint on where it stands in CAD evaluation and if it will remain relevant as a diagnostic modality or be retired going forward. We also provide our perspectives on how sECG can co-exist with other modalities such as calcium scoring and discuss the role of such testing in the Indian population.

Clinical experience with regadenoson SPECT myocardial perfusion imaging: insights into patient characteristics, safety, and impact of results on clinical management.

The Henry Ford Hospital (HFH) regadenoson (REG) registry includes patients with a variety of comorbidities allowing for the evaluation of outcomes in a large, unselected population. Using a database of electronic medical records and nuclear cardiology reports, patients aged > 18 years who underwent REG-facilitated single-photon emission computed tomography (SPECT) testing at HFH between January 2009 and August 2012 were identified. The primary objective was to describe the clinical and demographic characteristics of patients who had undergone REG only vs REG WALK (REG + low-level exercise) SPECT. A total of 2104 patients were included in the analysis (mean age 65.3 years; 50% women; 51% African American, 43% Caucasian). For the REG only (n = 1318) and REG WALK (n = 786) cohorts, SPECT was abnormal in 37% of patients (REG only, 39%; REG WALK, 34%; P < 0.01). No differences in diagnostic modalities or interventions in 90 days after SPECT were observed. Immediate safety analysis showed no deaths 48 h after REG SPECT testing. Although they guide invasive therapy, abnormal scans do not automatically lead to invasive testing. This demonstrates the focus on initial medical management, which reflects the existing evidence of initial goal-directed medical management of stable coronary disease.

Role of multimodality imaging in ischemic and non-ischemic cardiomyopathy.

Chronic heart failure (CHF) is a major and growing problem in the western hemisphere, affecting about 5 million patients in the United States. In daily practice patients with left ventricular systolic dysfunction (LVSD) and significant angiographic coronary artery disease (CAD) are felt to have an ischemic cardiomyopathy (ICMP) and those without CAD or mild-moderate CAD out of proportion to the extent of LVSD are felt to have a non-ischemic cardiomyopathy (NICMP). Although invasive coronary angiography is the gold standard for the diagnosis of CAD, recent advances in non-invasive imaging have created multiple options for evaluating ICMP and NICMP. This review details the role of cardiac imaging in the diagnosis of ICMP and NICMP and outlines an algorithm of use of non-invasive tests in asymtomatic LVSD and symptomatic heart failure.

Clinical impact of pre-kidney transplant pulmonary hypertension on post-transplant outcomes.

Outcomes of kidney transplant (KT) patients with pre-transplant pulmonary hypertension (PH) are poorly understood. PH patients are often considered high risk and excluded from KT. We investigated the association of pre-transplant PH with KT recipient's outcomes. A single-center, retrospective study that reviewed all patients transplanted from 2010 to 2016, who had a transthoracic echocardiogram (TTE) before KT and at least one TTE post-KT. The TTE closest to the KT was used for analyses. PH is defined as pulmonary artery systolic pressure (PASP) ≥ 40 mm Hg. Of 204 patients, 61 had PASP ≥ 40 mm Hg (with PH) and 143 had PASP < 40 mm Hg (without PH) prior to KT. No statistically significant differences existed between the two groups in baseline demographics, renal failure etiologies, dialysis access type, and cardiovascular risk factors. The mean difference in pre-KT PASP was 18.1 ± 7 mm Hg (P < 0.001). Patients with PH had a statistically significant decrease in PASP post-KT compared to the patients without PH with a mean change of -7.03 ± 12.28 mm Hg vs. + 3.96 ± 11.98 mm Hg (p < 0.001), respectively. Moderate mitral and moderate-severe tricuspid regurgitation were the only factors found to be independently associated with PH (p = 0.001) on multivariable analysis. No statistically significant difference was notable in patient survival, graft function, and creatinine post-KT in both groups. PH pre-KT particularly mild-moderate PH did not adversely affect intermediate (90-day) and long-term allograft and patient survival. Patients with mild-moderate PH should not be excluded from KT.

Eighty-two-year-old man with a systolic murmur.

CLINICAL INTRODUCTION: An 82-year-old man with a history of coronary artery bypass surgery, hypertension and small bowel gastrointestinal stromal tumour underwent cardiac risk evaluation prior to surgical resection of his tumour. He was asymptomatic from a cardiovascular perspective, but his activity level was less than four metabolic equivalents. Physical examination was notable for a 2/6 systolic murmur at the apex. ECG showed sinus rhythm. A transthoracic echocardiogram was performed (figure 1 and online supplementary video 1).DC1SP110.1136/heartjnl-2018-313413.supp1Supplementary file 1 heartjnl;104/22/1887/F1F1F1Figure 1Transthoracic echocardiography. (A) Mitral valve continuous wave Doppler and (B) tricuspid valve continuous wave Doppler. QUESTION: The findings in figure 1 are most likely due to which of the following?Atrioventricular conduction block.Acute severe aortic regurgitation.Patent ductus arteriosus.Atrial flutter.Severe mitral stenosis.

Comparison of treadmill exercise versus dipyridamole stress with myocardial perfusion imaging using rubidium-82 positron emission tomography.

OBJECTIVES: This study assessed the feasibility of treadmill exercise rubidium-82 ((82)Rb) positron emission tomography (PET) and compared image quality and diagnostic content with dipyridamole (82)Rb PET in patients referred for evaluation of coronary artery disease (CAD). BACKGROUND: Dipyridamole stress (82)Rb PET myocardial perfusion imaging (MPI) is an accurate imaging modality used to diagnose CAD and determine prognosis. Although pharmacologic stress is used routinely, exercise treadmill stress may be an alternative and provide clinical information helpful to decision making, particularly for patients unwilling or unable to tolerate pharmacologic stress. METHODS: Fifty patients (mean age, 60 +/- 10 years; 47 men) underwent treadmill exercise and dipyridamole (82)Rb PET. Images were assessed: 1) qualitatively using a 17-segment model and a semiquantitative visual score on a five-point scale and with calculation of summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS); and 2) quantitatively with a 70% threshold for abnormal perfusion and expressed as extent of abnormal perfusion (% left ventricular). RESULTS: Treadmill exercise was preferred by 74% of patients (37 of 50, p < 0.001). The exercise and dipyridamole (82)Rb PET summed scores and quantitative extent of abnormal perfusion were very similar and highly correlated. Results of Bland-Altman analysis showed no significant bias. Image quality was superior with exercise stress with greater myocardial uptake and higher target to background ratios. CONCLUSIONS: Treadmill exercise (82)Rb PET is feasible and provides imaging results of similar diagnostic content and superior image quality compared with dipyridamole stress. Treadmill exercise is a reasonable alternative to pharmacologic stress with (82)Rb PET MPI.