Quantification of intramyocardial blood volume using 99mTc-RBC SPECT/CT: a pilot human study.

BACKGROUND: Quantification of intramyocardial blood volume (IMBV), the fraction of myocardium that is occupied by blood, is a promising Index to measure microcirculatory functions. In previous large animal SPECT/CT studies injected with 99mTc-labeled Red Blood Cell (RBC) and validated by ex vivo microCT, we have demonstrated that accurate IMBV can be measured. In this study, we report the data processing methods and results of the first-in-human pilot study. METHODS: Data from three subjects have been included to date. Each subject underwent rest and adenosine-induced stress 99mTc-RBC SPECT/CT on a dedicated cardiac system with both non-contrast and contrast-enhanced CT acquired. Corrections of attenuation (AC) and scatter (SC), respiratory and cardiac gating, and partial volume correction (PVC) were applied. We also performed automatic segmentation and registration approach based on the blood pool topology in both SPECT and CT images. RESULTS: The quantified IMBV across all subjects under resting conditions were 35.0% ± 3.3% for the end-diastolic phase and 24.1% ± 2.7% for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) between diastolic and systolic phases was 31.5% ± 3.0%. Under stress, IMBV were 40.6% ± 4.2% for the end-diastolic phase and 26.5% ± 2.8% for the end-systolic phase, and ΔIMBV was 34.7% ± 7.4%. CONCLUSIONS: It is feasible to quantify IMBV in resting and stress conditions in human studies using SPECT/CT with 99mTc-RBC.

Nuclear cardiology in the context of multimodality imaging to detect cardiac toxicity from cancer therapeutics: Established and emerging methods.

The complexity of cancer therapies has vastly expanded in the last decade, along with type and severity of cardiac toxicities associated with these treatments. Prevention of pre-clinical cardiotoxicity may improve cardiovascular outcomes and circumvent the decision to place life-sustaining chemotherapeutic agents on hold, making the early detection of cancer therapeutic related cardiac toxicity with non-invasive imaging essential to the care of these patients. There are several established methods of cardiac imaging in the areas of nuclear cardiology, echocardiography, computed tomography, and cardiac magnetic resonance imaging that are used to assess for cardiovascular toxicity of cancer treatments, with several methods under development. The following review will provide an overview of current and emerging imaging techniques in these areas.

Prognostic and functional implications of left atrial late gadolinium enhancement cardiovascular magnetic resonance.

BACKGROUND: Left atrial (LA) late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is indicative of fibrosis, and has been correlated with reduced LA function, increased LA volume, and poor procedural outcomes in cohorts with atrial fibrillation (AF). However, the role of LGE as a prognostic biomarker for arrhythmia in cardiac disease has not been examined. METHODS: In this study, we assessed LA LGE using a 3D LGE CMR sequence to examine its relationships with new onset atrial arrhythmia, and LA and left ventricular (LV) mechanical function. RESULTS: LA LGE images were acquired in 111 patients undergoing CMR imaging, including 66 patients with no prior history of an atrial arrhythmia. During the median follow-up of 2.7 years (interquartile range (IQR) 1.8-3.7 years), 15/66 (23%) of patients developed a new atrial arrhythmia. LA LGE ≥10% of LA myocardial volume was significantly associated with an increased rate of new-onset atrial arrhythmia, with a hazard ratio of 3.16 (95% CI 1.14-8.72), p = 0.026. There were significant relationships between LA LGE and both LA ejection fraction (r = - 0.39, p < 0.0005) and echocardiographic LV septal e' (r = - 0.24, p = 0.04) and septal E/e' (r = 0.31, p = 0.007). CONCLUSIONS: Elevated LA LGE is associated with reduced LA function and reduced LV diastolic function. LA LGE is associated with new onset atrial arrhythmia during follow-up.

Appropriate Use Criteria for Coronary Revascularization and Trends in Utilization, Patient Selection, and Appropriateness of Percutaneous Coronary Intervention.

IMPORTANCE: Appropriate Use Criteria for Coronary Revascularization were developed to critically evaluate and improve patient selection for percutaneous coronary intervention (PCI). National trends in the appropriateness of PCI have not been examined. OBJECTIVE: To examine trends in PCI utilization, patient selection, and procedural appropriateness following the introduction of Appropriate Use Criteria. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, longitudinal, cross-sectional analysis of patients undergoing PCI between July 1, 2009, and December 31, 2014, at hospitals continuously participating in the National Cardiovascular Data Registry CathPCI registry over the study period. MAIN OUTCOMES AND MEASURES: Proportion of nonacute PCIs classified as inappropriate at the patient and hospital level using the 2012 Appropriate Use Criteria for Coronary Revascularization. RESULTS: A total of 2.7 million PCI procedures from 766 hospitals were included. Annual PCI volume of acute indications was consistent over the study period (377,540 in 2010; 374,543 in 2014), but the volume of nonacute PCIs decreased from 89,704 in 2010 to 59,375 in 2014. Among patients undergoing nonacute PCI, there were significant increases in angina severity (Canadian Cardiovascular Society grade III/IV angina, 15.8% in 2010 and 38.4% in 2014), use of antianginal medications prior to PCI (at least 2 antianginal medications, 22.3% in 2010 and 35.1% in 2014), and high-risk findings on noninvasive testing (22.2% in 2010 and 33.2% in 2014) (P < .001 for all), but only modest increases in multivessel coronary artery disease (43.7% in 2010 and 47.5% in 2014, P < .001). The proportion of nonacute PCIs classified as inappropriate decreased from 26.2% (95% CI, 25.8%-26.6%) to 13.3% (95% CI, 13.1%-13.6%), and the absolute number of inappropriate PCIs decreased from 21,781 to 7921. Hospital-level variation in the proportion of PCIs classified as inappropriate persisted over the study period (median, 12.6% [interquartile range, 5.9%-22.9%] in 2014). CONCLUSIONS AND RELEVANCE: Since the publication of the Appropriate Use Criteria for Coronary Revascularization in 2009, there have been significant reductions in the volume of nonacute PCI. The proportion of nonacute PCIs classified as inappropriate has declined, although hospital-level variation in inappropriate PCI persists.

Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease.

In coronary artery disease (CAD), endothelin-1 (ET-1) is released by activated macrophages and thereby contributes to coronary plaque rupture and triggered cardiac events. The multifactorial regulation of ET-1 includes stimulated release by cytokines and autonomic factors. Laboratory stress provokes alteration in autonomic tone and prolonged ET-1 mediated endothelial dysfunction. The objective of the study is to determine the autonomic contribution to an increase in ET-1 in response to laboratory stress in patients with CAD. Patients (n = 88) with chronic stable CAD instrumented with hemodynamic monitor, digital electrocardiogram (ECG) monitor and indwelling catheter for blood sampling completed a laboratory protocol that included initial rest (30 min), baseline (BL: 10 min), and anger recall stress (AR: 8 min). Change from BL to AR was determined for (a) parasympathetic activity (by spectral analysis of ECG); (b) sympathetic activity (by circulating catecholamines); and (c) ET-1. AR provoked increases from BL in catecholamines, and a decrease in parasympathetic activity. Multivariate analysis with change in parasympathetic activity and catecholamines, while controlling for age and use of ß-blockers, revealed a significant odds ratio (OR = 3.27, 95% CI 1.03, 10.41 P = 0.04) for an increase in ET-1 associated with parasympathetic withdrawal; no other variables were significant. The predominant influence of parasympathetic activity on anger/stress-provoked increase in ET-1 is consistent with the cholinergic antiinflammatory pathway. Future examination of autonomic influences on atherosclerotic leukocytes, endothelial cell function and the dynamics of ET-1 are warranted.

Rationale and proposed framework for shared decision making in cardio-oncology.

Physicians have a duty to present diagnostic and therapeutic choices with rational guidance that respects patient values and realizes patient goals. In cardio-oncology, we commonly encounter patients who understandably feel overwhelmed or feel that they have no favorable options, particularly in the context of advanced malignancy. Accordingly, a longitudinal multidisciplinary commitment to shared decision making (SDM) ensures that physicians and patients actively participate in this process to promote the best possible outcomes from the patient perspective. We propose a practical framework for approaching these difficult decisions in cardio-oncology drawing upon our experience in clinical practice.

Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. METHODS: We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. RESULTS: Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of -9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at -12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = -0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = -0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. CONCLUSION: In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Tendency to angry rumination predicts stress-provoked endothelin-1 increase in patients with coronary artery disease.

OBJECTIVE: To determine whether a tendency to angry rumination predicts anger recall (AR) stress-provoked increase in endothelin (ET)-1 among patients with coronary heart disease (CHD). METHODS: Patients with chronic stable CHD (n = 105) completed a five-item measure of tendency to angry rumination (DAB-VR) and underwent a laboratory AR stress protocol (15-minute resting baseline [BL], 8-minute AR). Blood samples drawn at end of BL and AR were assayed for ET-1. Change in ET-1 from BL to AR (increase versus decrease/no change) was treated dichotomously in multivariate logistic regression models, including DAB-VR score and potential confounders, to evaluate the contribution of DAB-VR to the prediction of change in ET-1. RESULTS: In the multivariate model, DAB-VR score significantly predicted ET-1 increase (odds ratio, 1.34; 95% confidence interval, 1.10-1.1.63; p = .004), controlling for age, history of diabetes, hypercholesterolemia, rate pressure product, use of beta blockers, and statins. CONCLUSIONS: A tendency to angry rumination independently predicted AR stress-provoked ET-1 increase among patients with CHD. Given the involvement of ET-1 in plaque rupture, anger rumination tendency may identify vulnerability to anger-triggered acute coronary syndrome through prolongation of initial anger mobilization. The contribution of ruminative thinking to sustained poststress ET-1 elevation and the synergistic relationship of ET-1 during emotional stress with norepinephrine and nitric oxide remain to be explored.

Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure: A U.S. Center's Experience.

OBJECTIVES: The purpose of this study was to investigate real world safety and efficacy of hypertonic saline therapy in cases of refractory acute decompensated heart failure (ADHF) at a large U.S. academic medical center. BACKGROUND: Hypertonic saline therapy has been described as a potential management strategy for refractory ADHF, but experience in the United States is limited. METHODS: A retrospective analysis was performed in all patients receiving hypertonic saline for diuretic therapy-resistant ADHF at the authors' institution since March 2013. The primary analytic approach was a comparison of the trajectory of clinical variables prior to and after administration of hypertonic saline, with secondary focus on predictors of treatment response. RESULTS: A total of 58 hypertonic saline administration episodes were identified across 40 patients with diuretic-therapy refractory ADHF. Prior to hypertonic saline administration, serum sodium, chloride, and creatinine concentrations were worsening but improved after hypertonic saline administration (p < 0.001, all). Both total urine output and weight loss significantly improved with hypertonic saline (p = 0.01 and <0.001, respectively). Diuretic efficiency, defined as change in urine output per doubling of diuretic dose, also improved over this period (p < 0.01). There were no significant changes in respiratory status or overcorrection of serum sodium with the intervention. CONCLUSIONS: In a cohort of patients who were refractory to ADHF, hypertonic saline administration was associated with increased diuretic efficiency, fluid and weight loss, and improvement of metabolic derangements, and no adverse respiratory or neurological signals were identified. Additional study of hypertonic saline as a diuretic adjuvant is warranted.

The Role of Cardiac Magnetic Resonance Imaging to Detect Cardiac Toxicity From Cancer Therapeutics.

PURPOSE OF REVIEW: The emerging complexity of cardiac toxicity caused by cancer therapies has created demand for more advanced non-invasive methods to better evaluate cardiac structure, function, and myocardial tissue characteristics. Cardiac magnetic resonance imaging meets these needs without exposure to ionizing radiation, and with superior spatial resolution. RECENT FINDINGS: Special applications of cardiac magnetic resonance (CMR) to assess for cancer therapy-induced cardiac toxicity include the detection of subclinical LV dysfunction through novel methods of measuring myocardial strain, detection of microcirculatory dysfunction, identification of LV and LA fibrosis, and more sensitive detection of inflammation caused by immune checkpoint inhibitors. CMR plays a significant role in the non-invasive workup of cardiac toxicity from cancer therapies, with recent advancements in the field that have opened avenues for further research and development.

Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.

A Blueprint for the Post Discharge Clinic Visit after an Admission for Heart Failure.

The immense symptom burden and healthcare expenditure associated with heart failure (HF) has resulted in hospital systems, insurance companies, and federal agencies playing close attention to systems of care delivery. In particular, there has been a large extent of focus on decreasing the frequency of HF readmissions through the development of hospital quality measures and the expansion of post discharge services to improve transitions of care from the inpatient to the outpatient setting. The post discharge clinic visit (PDV) serves an important role in this process as it acts as a fulcrum for the multi-disciplinary services available to HF patients, as well as an opportunity to fill any gaps that might have occurred in evidence based care of the patient. The objective of this review is to provide a blueprint for the PDV that will allow clinicians to construct the key elements of the PDV in a patient-centered fashion that is firmly rooted in the guidelines.