Functional Effects of Cardiomyocyte Injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.

Assessment and validation of a novel fast fully automated artificial intelligence left ventricular ejection fraction quantification software.

BACKGROUND: Quantification of left ventricular ejection fraction (LVEF) by transthoracic echocardiography (TTE) is operator-dependent, time-consuming, and error-prone. LVivoEF by DIA is a new artificial intelligence (AI) software, which displays the tracking of endocardial borders and rapidly quantifies LVEF. We sought to assess the accuracy of LVivoEF compared to cardiac magnetic resonance imaging (cMRI) as the reference standard and to compare LVivoEF to the standard-of-care physician-measured LVEF (MD-EF) including studies with ultrasound enhancing agents (UEAs). METHODS: In 273 consecutive patients, we compared MD-EF and AI-derived LVEF to cMRI. AI-derived LVEF was obtained from a non-UEA four-chamber view without manual correction. Thirty-one patients were excluded: 25 had interval interventions or incomplete TTE or cMRI studies and six had uninterpretable non-UEA apical views. RESULTS: In the 242 subjects, the correlation between AI and cMRI was r = .890, similar to MD-EF and cMRI with r = .891 (p = 0.48). Of the 126 studies performed with UEAs, the correlation of AI using the unenhanced four-chamber view was r = .89, similar to MD-EF with r = .90. In the 116 unenhanced studies, AI correlation was r = .87, similar to MD-EF with r = .84. From Bland-Altman analysis, LVivoEF underreported the LVEF with a bias of 3.63 ± 7.40% EF points compared to cMRI while MD-EF to cMRI had a bias of .33 ± 7.52% (p = 0.80). CONCLUSIONS: Compared to cMRI, LVivoEF can accurately quantify LVEF from a standard apical four-chamber view without manual correction. Thus, LVivoEF has the ability to improve and expedite LVEF quantification.

Using Clinical and Echocardiographic Characteristics to Characterize the Risk of Ischemic Stroke in Patients with COVID-19.

BACKGROUND: COVID-19 has been associated with an increased incidence of ischemic stroke. The use echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19 has not been explored. METHODS: We conducted a retrospective study of 368 patients hospitalized between 3/1/2020 and 5/31/2020 who had laboratory-confirmed infection with SARS-CoV-2 and underwent transthoracic echocardiography during hospitalization. Patients were categorized according to the presence of ischemic stroke on cerebrovascular imaging following echocardiography. Ischemic stroke was identified in 49 patients (13.3%). We characterized the risk of ischemic stroke using a novel composite risk score of clinical and echocardiographic variables: age <55, systolic blood pressure >140 mmHg, anticoagulation prior to admission, left atrial dilation and left ventricular thrombus. RESULTS: Patients with ischemic stroke had no difference in biomarkers of inflammation and hypercoagulability compared to those without ischemic stroke. Patients with ischemic stroke had significantly more left atrial dilation and left ventricular thrombus (48.3% vs 27.9%, p = 0.04; 4.2% vs 0.7%, p = 0.03). The unadjusted odds ratio of the composite novel COVID-19 Ischemic Stroke Risk Score for the likelihood of ischemic stroke was 4.1 (95% confidence interval 1.4-16.1). The AUC for the risk score was 0.70. CONCLUSIONS: The COVID-19 Ischemic Stroke Risk Score utilizes clinical and echocardiographic parameters to robustly estimate the risk of ischemic stroke in patients hospitalized with COVID-19 and supports the use of echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19.

Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification.

BACKGROUND: A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. METHODS: Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. RESULTS: A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as "needing" and "not needing" rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either "needing" (n = 28) or "not needing" (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either "needing" (n = 31) or "not needing" (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite sensitivity, specificity, PPV, and NPV were 83.3%, 99.5%, 97.2%, and 96.7%, respectively. CONCLUSION: Technologists and automated quantification software had a high degree of agreement with the clinical reference standard for determining the need for rest images in a stress-first imaging protocol. Utilizing an experienced technologist and automated systems to screen stress-first images could expand the use of stress-first MPI to sites where the cardiologist is not immediately available for interpretation.

The prevalence of metabolic syndrome among law enforcement officers who responded to the 9/11 World Trade Center attacks.

BACKGROUND: Law enforcement officers (LEOs) experience high rates of cardiovascular events compared with the general US population. Metabolic syndrome (MetS) confers an increased risk of cardiovascular disease and all-cause mortality. Data regarding MetS among LEOs are limited. METHODS: We sought to determine the prevalence of MetS and its associated risk factors as well as gender differences among LEOs who participated in the World Trade Center (WTC) Law Enforcement Cardiovascular Screening (LECS) Program from 2008 to 2010. We evaluated a total of 2,497 participants, 40 years and older, who responded to the 9/11 WTC attacks. RESULTS: The prevalence of MetS was 27%, with abdominal obesity and hypertension being the most frequently occurring risk factors. MetS and its risk factors were significantly higher among male compared to female LEOs, except for reduced HDL-cholesterol levels. CONCLUSIONS: MetS is a rising epidemic in the United States, and importantly, approximately one in four LEOs who worked at the WTC site after 9/11 are affected. Am. J. Ind. Med. 59:752-760, 2016. © 2016 Wiley Periodicals, Inc.

Prospective evaluation of a new protocol for the provisional use of perfusion imaging with exercise stress testing.

PURPOSE: Previous literature suggests that myocardial perfusion imaging (MPI) adds little to the prognosis of patients who exercise >10 metabolic equivalents (METs) during stress testing. With this in mind, we prospectively tested a provisional injection protocol in emergency department (ED) patients presenting for the evaluation of chest pain in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. METHODS: All patients who presented to the ED over a 5-year period who were referred for stress testing as part of their ED evaluation were included. Patients considered for a provisional protocol were: exercise stress, age <65 years, no known coronary artery disease, and an interpretable rest ECG. Criteria for not injecting included a maximal predicted heart rate ≥85%, ≥10 METs of exercise, no anginal symptoms during stress, and no ECG changes. Groups were compared based on stress test results, all-cause and cardiac mortality, follow-up cardiac testing, subsequent revascularization, and cost. RESULTS: A total of 965 patients were eligible with 192 undergoing exercise-only and 773 having perfusion imaging. After 41.6 ± 19.6 months of follow-up, all-cause mortality was similar in the exercise-only versus the exercise plus imaging group (2.6% vs. 2.1%, p = 0.59). There were no cardiac deaths in the exercise-only group. At 1 year there was no difference in the number of repeat functional stress tests (1.6% vs. 2.1%, p = 0.43), fewer angiograms (0% vs. 4.0%, p = 0.002), and a significantly lower cost ($65 ± $332 vs $506 ± $1,991, p = 0.002; values are in US dollars) in the exercise-only group. The radiation exposure in the exercise plus imaging group was 8.4 ± 2.1 mSv. CONCLUSIONS: A provisional injection protocol has a very low mortality, few follow-up diagnostic tests, and lower cost compared to standard imaging protocols. If adopted it would decrease radiation exposure, save time and decrease health-care costs without jeopardizing prognosis.

Carcinoid Heart Disease without Liver Involvement Caused by a Primary Ovarian Carcinoid Tumour.

Carcinoid heart disease, caused by primary ovarian carcinoid tumour, is a rare form of valvular heart disease. This form of heart disease usually presents with symptoms of right-sided valvular dysfunction, ultimately leading to right-sided heart failure. This entity is unique as it develops in the absence of liver metastasis. We report a case of 75 year-old woman with primary ovarian carcinoid tumour who presented with symptoms of severe right-sided heart failure and successfully underwent pulmonic and tricuspid valve replacement along with a right ventricular (RV) outflow patch enlargement. This patient later underwent uneventful resection of the primary ovarian carcinoid tumour, with complete resolution of her symptoms.

Platelet TGF-ß1 contributions to plasma TGF-ß1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload.

Circulating platelets contain high concentrations of TGF-ß1 in their α-granules and release it on platelet adhesion/activation. We hypothesized that uncontrolled in vitro release of platelet TGF-ß1 may confound measurement of plasma TGF-ß1 in mice and that in vivo release and activation may contribute to cardiac pathology in response to constriction of the transverse aorta, which produces both high shear and cardiac pressure overload. Plasma TGF-ß1 levels in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were much higher than those obtained when prostaglandin E1 was added to inhibit release or when blood was collected percutaneously from the left ventricle under ultrasound guidance. Even with optimal blood drawing, plasma TGF-ß1 was lower in mice rendered profoundly thrombocytopenic or mice with selectively low levels of platelet TGF-ß1 because of megakaryocyte-specific disruption of their TGF-ß1 gene (Tgfb1(flox)). Tgfb1(flox) mice were also partially protected from developing cardiac hypertrophy, fibrosis, and systolic dysfunction in response to transverse aortic constriction. These studies demonstrate that plasma TGF-ß1 levels can be assessed accurately, but it requires special precautions; that platelet TGF-ß1 contributes to plasma levels of TGF-ß1; and that platelet TGF-ß1 contributes to the pathologic cardiac changes that occur in response to aortic constriction.

A simple scoring tool for the evaluation of patients in an emergency department chest pain unit.

BACKGROUND: There are multiple risk scores to determine the prognosis of high-risk patients presenting with acute coronary syndromes (ACS) to emergency departments (ED) and chest pain units (CPU), however, there are few options for patients without ACS (no diagnostic ST-segment deviation or positive biomarkers). OBJECTIVES: To derive a clinical risk score for the management of lower-risk patients seen in ED CPUs. METHODS: We evaluated all patients triaged through the Mount Sinai ED CPU over a 76-month period who underwent stress testing after negative serial biomarkers and ECGs. Primary and secondary endpoints of hospital admission and coronary revascularization were retrospectively obtained. Variables associated with admission at P < 0.1 level were entered into a multivariable model. Each variable was assigned an integer score based on the beta coefficients in the final model. RESULTS: A total of 4,666 patients were evaluated and 738 (15.8%) had an abnormal stress test, 575 (12.3%) were admitted to the hospital, and 133 (2.9%) underwent coronary revascularization. A score consisting of age > 55 years, gender, chest pain quality (typical vs atypical), known coronary artery disease, shortness of breath, diabetes, smoking, and abnormal ECG demonstrated strong correlation between observed vs predicted hospital admission. The clinical score showed good ability to predict admission with a receiver operating characteristic (ROC) area of 0.72, which improved to 0.81 when the results of stress testing were added. CONCLUSIONS: This new clinical risk score is simple to use, predicts a clinically relevant outcome to ED physicians, and the results of noninvasive testing are additive.

Local large language models for privacy-preserving accelerated review of historic echocardiogram reports.

OBJECTIVES: The study developed framework that leverages an open-source Large Language Model (LLM) to enable clinicians to ask plain-language questions about a patient's entire echocardiogram report history. This approach is intended to streamline the extraction of clinical insights from multiple echocardiogram reports, particularly in patients with complex cardiac diseases, thereby enhancing both patient care and research efficiency. MATERIALS AND METHODS: Data from over 10 years were collected, comprising echocardiogram reports from patients with more than 10 echocardiograms on file at the Mount Sinai Health System. These reports were converted into a single document per patient for analysis, broken down into snippets and relevant snippets were retrieved using text similarity measures. The LLaMA-2 70B model was employed for analyzing the text using a specially crafted prompt. The model's performance was evaluated against ground-truth answers created by faculty cardiologists. RESULTS: The study analyzed 432 reports from 37 patients for a total of 100 question-answer pairs. The LLM correctly answered 90% questions, with accuracies of 83% for temporality, 93% for severity assessment, 84% for intervention identification, and 100% for diagnosis retrieval. Errors mainly stemmed from the LLM's inherent limitations, such as misinterpreting numbers or hallucinations. CONCLUSION: The study demonstrates the feasibility and effectiveness of using a local, open-source LLM for querying and interpreting echocardiogram report data. This approach offers a significant improvement over traditional keyword-based searches, enabling more contextually relevant and semantically accurate responses; in turn showing promise in enhancing clinical decision-making and research by facilitating more efficient access to complex patient data.

A hypothetical protocol for the provisional use of perfusion imaging with exercise stress testing.

BACKGROUND: Previous literature suggests that the results of myocardial perfusion imaging (MPI) add little to the prognosis of patients who exercise >10 metabolic equivalents (METS) during stress testing. With this in mind, we attempted to determine if a provisional injection protocol could be developed in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. This protocol would save a substantial amount of time, radiation exposure, and cost. METHODS: All patients who underwent a stress SPECT MPI over a 6.5-year period from 2004 to 2010 were included. Patients who would have been considered for a standby injection protocol were: exercise stress, age < 65, no known coronary artery disease (CAD), and an interpretable ECG. Patients were retrospectively divided into two groups based on whether they would have received radioisotope or not. Criteria for not injecting included a maximal predicted heart rate ≥ 85%, ≥10 METS of exercise, no symptoms of chest pain or shortness of breath, and no ECG changes (ST depression or arrhythmia). The two groups were then compared based on MPI results and all-cause mortality derived from the Social Security Death Index. RESULTS: A total of 24,689 patients underwent SPECT MPI during this period, and 5,352 would have been eligible for a provisional injection protocol. There were 3,791 (70.8%), who would have been injected and 1,561 (29.2%), who would not have been. Perfusion results were abnormal in 5.9% of non-injected group compared to 14.4% in those who would have been injected. After a mean follow-up of 60.6 ± 21.4 months, 1.1% had died in the non-injected cohort compared to 2.2% in the injected group. CONCLUSION: A provisional injection protocol defined as age < 65, normal rest ECG, no history of CAD, and high level exercise with a negative ECG response and no symptoms has a very low 5-year all-cause mortality and low yield of MPI. If adopted it would decrease radiation exposure and save time and health care costs without jeopardizing prognosis.

High-efficiency SPECT MPI: comparison of automated quantification, visual interpretation, and coronary angiography.

BACKGROUND: Recently introduced high-efficiency (HE) SPECT cameras with solid-state CZT detectors have been shown to decrease imaging time and reduce radiation exposure to patients. An automated, computer-derived quantification of HE MPI has been shown to correlate well with coronary angiography on one HE SPECT camera system (D-SPECT), but has not been compared to visual interpretation on any of the HE SPECT platforms. METHODS: Patients undergoing a clinically indicated Tc-99m sestamibi HE SPECT (GE Discovery 530c with supine and prone imaging) study over a 1-year period followed by a coronary angiogram within 2 months were included. Only patients with a history of CABG surgery were excluded. Both MPI studies and coronary angiograms were reinterpreted by blinded readers. One hundred and twenty two very low (risk of CAD < 5%) or low (risk of CAD < 10%) likelihood subjects with normal myocardial perfusion were used to create normal reference limits. Computer-derived quantification of the total perfusion deficit at stress and rest was obtained with QPS software. The visual and automated MPI quantification were compared to coronary angiography (≥70% luminal stenosis) by receiver operating curve (ROC) analysis. RESULTS: Of the 3,111 patients who underwent HE SPECT over a 1-year period, 160 patients qualified for the correlation study (66% male, 52% with a history of CAD). The ROC area under the curve (AUC) was similar for both the automated and the visual interpretations using both supine only and combined supine and prone images (0.69-0.74). Using thresholds determined from sensitivity and specificity curves, the automated reads showed higher specificity (59%-67% vs 27%-60%) and lower sensitivity (71%-72% vs 79%-93%) than the visual reads. By including prone images sensitivity decreased slightly but specificity increased for both. By excluding patients with known CAD and cardiomyopathies, AUC and specificity increased for both techniques (0.72-0.82). The use of a difference score to evaluate ischemic burden resulted in lower sensitivities but higher specificities for both automated and visual quantification. There was good agreement between the visual interpretation and automated quantification in the entire cohort of 160 unselected consecutive patients (r = 0.70-0.81, P < .0001). CONCLUSIONS: Automated and visual quantification of high-efficiency SPECT MPI with the GE Discovery camera provides similar overall diagnostic accuracy when compared to coronary angiography. There was good correlation between the two methods of assessment. Combined supine and prone stress imaging provided the best diagnostic accuracy.

Validation of American Society of Echocardiography Guideline-Recommended Parameters of Right Ventricular Dysfunction Using Artificial Intelligence Compared With Cardiac Magnetic Resonance Imaging.

BACKGROUND: Right ventricular (RV) function is important in the evaluation of cardiac function, but its assessment using standard transthoracic echocardiography (TTE) remains challenging. Cardiac magnetic resonance imaging (CMR) is considered the gold standard. The American Society of Echocardiography recommends surrogate measures of RV function and RV ejection fraction (RVEF) by TTE, including fractional area change (FAC), free wall strain (FWS), and tricuspid annular planar systolic excursion (TAPSE), but they require technical expertise in acquisition and quantification. METHODS: The aim of this study was to evaluate the sensitivity, specificity, and positive and negative predictive values of FAC, FWS, and TAPSE derived using a rapid, novel artificial intelligence (AI) software (LVivoRV) from a single-plane transthoracic echocardiographic apical four-chamber, RV-focused view without ultrasound-enhancing agents for detecting abnormal RV function compared with CMR-derived RVEF. RV dysfunction was defined as RVEF < 50% and RVEF < 40% on CMR. RESULTS: TTE and CMR were performed within a median of 10 days (interquartile range, 2-32 days) of each other in 225 consecutive patients without interval procedural or pharmacologic intervention. The sensitivity and negative predictive value to detect CMR-defined RV dysfunction when all three AI-derived parameters (FAC, FWS, and TAPSE) were abnormal were 91% and 96%, while those of expert physician reads were 91% and 97%. Specificity and positive predictive value were lower (50% and 32%) compared with expert physician-read echocardiograms (82% and 56%). CONCLUSIONS: AI-derived measurements of FAC, FWS, and TAPSE had excellent sensitivity and negative predictive value for ruling out significant RV dysfunction (CMR RVEF < 40%), comparable with that of expert physician readers, but lower specificity. Thus AI, using American Society of Echocardiography guidelines, may serve as a useful screening tool for rapid bedside assessment to exclude significant RV dysfunction.

A model for the prediction of a successful stress-first Tc-99m SPECT MPI.

BACKGROUND: Stress-only Tc-99m MPI saves time, radiation exposure, and a normal study has a benign prognosis. However, a stress-first protocol is relatively labor intensive requiring pre-test screening for suitability and early post-stress image review to determine the need for rest imaging. The purpose of this study was to develop a simple clinical score used prior to a patient's myocardial perfusion imaging (MPI) study to determine if they should undergo a stress-first protocol. METHODS: We reviewed all patients who underwent Tc-99m SPECT MPI over a 27-month period and divided them into derivation and validation cohorts. Patients were categorized as having a successful stress-first protocol based on a summed stress score ≤1, with or without attenuation correction. We generated a multivariable model from the derivation cohort to identify demographic and clinical correlates of successful stress-first imaging. Two validation cohorts using a CZT and a conventional SPECT camera were then used to test the performance of the model. RESULTS: The derivation cohort included 1,996 patients and the validation cohort consisted of 1,005 CZT SPECT patients and 2,430 conventional SPECT patients. The following variables were associated with unsuccessful (i.e., abnormal) stress-first imaging: age >65 years (1 point), diabetes (2 points), typical chest pain (2 points), congestive heart failure (3 points), abnormal ECG (4 points), male gender (4 points), and documented CAD (5 points). Emergency Department location (-2 points) was negatively associated with an unsuccessful protocol. An increasing score showed a strong association with an unsuccessful stress-first protocol in both the derivation and the validation cohorts (P < .0001) and dividing the cohorts into low (<5), intermediate (≥5 and <10), and high (≥10) risk scores accurately stratified patients based on their frequencies of unsuccessful stress-first imaging. ROC curve analysis showed excellent prediction in both the derivation and the validation cohorts with an area under the curve of 0.82 and 0.75-0.83, respectively. CONCLUSIONS: This pre-test scoring tool accurately identifies patients who can successfully undergo a stress-first imaging protocol without the need for rest imaging and may allow for wider adoption of stress-first imaging protocols.

The prognosis of a normal Tl-201 stress-only SPECT MPI study.

BACKGROUND: Stress-only Tc-99m SPECT myocardial perfusion imaging (MPI) decreases test time and patient radiation exposure with a proven benign prognosis of a normal study. The imaging sequence of Tl-201 MPI always starts with the stress portion; therefore, no pre-test decisions are needed regarding the imaging sequence. The recent intermittent Tc-99m shortage afforded the unique opportunity to study an unselected group of patients undergoing Tl-201 imaging. METHODS: We retrospectively reviewed all the patients who had SPECT MPI with Tc-99m or Tl-201 over a 1-year period. When Tc-99m was not available, patients received Tl-201. All stress Tl-201 images were routinely processed, and if normal, rest imaging was not done. When Tc-99m was used, patients with lower pre-test probability were selected for a stress-first protocol. We compared the all-cause mortality of patients with normal Tl-201 studies to those with normal stress-only and rest-stress Tc-99m studies using the Social Security Death Index. Unadjusted and risk-adjusted survival analysis was performed. Specific causes of death (cardiac or non-cardiac) were determined by medical record review and contact with treating physicians. RESULTS: A total of 3,658 patients underwent stress MPI during this time period. Of the 1,215 patients who had Tl-201 MPI, 716 (67%) had a normal stress-only study. Out of 2,443 patients who underwent Tc-99m MPI, 70% had normal perfusion with 1,098 normal stress-only studies and 493 normal rest-stress studies. The average follow-up was 23.3 ± 5.3 months. Unadjusted all-cause mortality at the end of follow-up was 7.1% in the Tl-201 stress-only group, 6.3% for Tc-99m stress-only patients, and 4.3% in the Tc-99m rest-stress cohort. After controlling for confounding variables, survival was similar in the three groups (HR 1.07, 95% CI 0.62-1.82, P = .82 for normal Tl-201 stress-only compared to normal Tc-99m rest-stress). The risk-adjusted 1-year survival was between 98.5 and 98.8% in the three groups. CONCLUSIONS: Normal stress-only Tl-201 SPECT MPI study has a similarly benign prognosis when compared to Tc-99m rest-stress and Tc-99m stress-only normal SPECT MPI studies. The stress-first design allowed for early triage of over 60% of patients and marked improvement in laboratory efficiency due to shortened test time.

Reduced stress dose with rapid acquisition CZT SPECT MPI in a non-obese clinical population: comparison to coronary angiography.

BACKGROUND: Cadmium Zinc Telluride (CZT) SPECT camera technology has the potential to reduce patient's radiation exposure and shorten imaging time. This study evaluated the correlation of low stress tracer dose, rapid CZT SPECT myocardial perfusion imaging (MPI) to coronary angiography in a <200-lbs population to further validate its ability to achieve both goals while preserving diagnostic accuracy. METHODS: All patients who had a low-dose stress (≤15 mCi) Tc-99m sestamibi SPECT MPI study using a CZT camera (GE Discovery NM 530c) with 3- to 5-minute image acquisition over a 2-year period followed by a coronary angiogram within 2 months were included. Patients with a history of coronary revascularization, left ventricular dysfunction, and LBBB or paced rhythms were excluded. Both MPI studies and coronary angiograms were interpreted by blinded readers and coronary artery disease (CAD) was defined as ≥70% stenosis. RESULTS: A total of 71 patients were included with a mean age of 64 years, 55% male, and a BMI of 25.4 kg/m(2) with an average stress dose of 13.3 mCi. Exercise stress was performed in 54% of patients and vasodilator pharmacologic stress in 46%. Sensitivity was 89%, specificity was 66%, and accuracy was 78% for detecting obstructive CAD. CONCLUSIONS: In this group of non-obese patients undergoing low stress dose imaging, high-efficiency CZT SPECT imaging demonstrated a high sensitivity, specificity, and accuracy for detecting obstructive epicardial CAD with a greatly reduced imaging time.

Obstructive sleep apnoea and left ventricular diastolic dysfunction among first responders to the 9/11 World Trade Center terrorist attack: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) is often linked to cardiovascular disease. A limited number of studies have reported an association between OSA and left ventricular diastolic dysfunction (LVDD). However, prior studies were performed on small patient populations. Studies have shown a high prevalence of OSA among first responders to the 9/11 World Trade Center (WTC) terrorist attack. We investigated the relationship between OSA and LVDD in a large population of WTC responders. DESIGN: Cross-sectional study. SETTING: One-time screening programme as part of the WTC-CHEST Study (NCT10466218), performed at a quaternary medical centre in New York City, from November 2011 to June 2014. PARTICIPANTS: A total of 1007 participants with mean age of 51 years of mostly non-Hispanic white men were evaluated. Patients from the WTC Health Program-Clinical Center of Excellence, who were over the age of 39 years, were eligible to participate. RESULTS: Evaluation of those without OSA diagnosis showed no significant association with LVDD when comparing those screened (Berlin Questionnaire) as OSA high risk versus OSA low risk (p=0.101). Among those diagnosed with LVDD, there was a significant association when comparing those with and without patient-reported OSA (OR 1.50, 95% CI 1.13 to 2.00, p=0.005), but the significance was not maintained after adjusting for pertinent variables (OR 1.3, 0.94 to 1.75, p=0.119). Notably, comparing those with OSA diagnosis and those low risk of OSA, the OR for LVDD was significant (1.69, 1.24 to 2.31, p=0.001), and after adjusting for waist-hip ratio, diabetes and coronary artery calcium score percentile, the relationship remained significant (OR 1.45, 1.03 to 2.04, p=0.032). CONCLUSION: The strong association of OSA with LVDD in this population may inform future guidelines to recommend screening for LVDD in high-risk asymptomatic patients with OSA.

Echocardiography in the time of Covid-19: Ultrasound enhancing agents save time and augment diagnostic information.

BACKGROUND: There are currently no clear guidelines regarding the use of ultrasound enhancing agents (UEAs) with transthoracic echocardiography (TTE) for patients hospitalized with Covid-19. We investigated whether the performance of TTE with UEAs provides more diagnostic information and allows for shorter acquisition time compared to unenhanced TTE imaging in this patient population. METHODS: We analyzed the TTEs of 107 hospitalized Covid-19 patients between April and June 2020 who were administered UEAs (Definity®, Lantheus). The time to acquire images with and without UEAs was calculated. A level III echocardiographer determined if new, clinically significant findings were visualized with the addition of UEAs. RESULTS: There was a mean of 11.84±3.59 UEA cineloops/study vs 20.74±8.10 non-UEA cineloops/study (p < 0.0001). Mean time to acquire UEA cineloop images was 72.28±28.18 s/study compared to 188.07±86.04 s/study for non-UEA cineloop images (p < 0.0001). Forty-eight patients (45%) had at least one new finding on UEA imaging, with a total of 62 new findings seen. New information gained with UEAs was more likely to be found in patients with acute respiratory distress syndrome (21 vs 9, p < 0.001) and in those on mechanical ventilation (21 vs 15, p = 0.046). CONCLUSIONS: TTE with UEAs required less time and fewer cineloop images compared to non-UEA imaging in patients hospitalized with Covid-19. Additionally, Covid-19 patients with severe respiratory disease benefited most with regard to new diagnostic information. Health care personnel should consider early use of UEAs in select hospitalized Covid-19 patients in order to reduce exposure and optimize diagnostic yield.

Reduced isotope dose and imaging time with a high-efficiency CZT SPECT camera.

BACKGROUND: In light of recent focus on diagnostic imaging, cardiac SPECT imaging needs to become a shorter test with lower radiation exposure to patients. Recently introduced Cadmium Zinc Telluride (CZT) cameras have the potential to achieve both goals. METHODS: During a 2-month period patients presenting for a Tc-99m sestamibi SPECT MPI study were imaged using a CZT camera using a low-dose rest-stress protocol (5 mCi rest and 15 mCi stress doses). Patients ≥250 lbs or a BMI ≥35 kg/m(2) were excluded. Rest images were processed at 5- and 8-minute acquisition times and stress images at 3- and 5-minute acquisition times. A subset of patients had stress imaging performed using both conventional and CZT SPECT cameras. Image acquisition times and SPECT camera images were compared based on total counts, count rate, image quality, and summed rest and stress scores. Twelve month clinical follow-up was also obtained. RESULTS: 131 patients underwent the study protocol (age 64.9 ± 9.8 years, 54.2% male). There was no significant difference in image quality and mean summed scores between 5- and 8-minute rest images and between 3- and 5-minute stress images. When compared to a conventional SPECT camera in 27 patients, total rest and stress perfusion deficits and calculated LVEF were similar (r = 0.94 and 0.96, respectively). At 12 months there was a benign prognosis in patients with normal perfusion. The effective dose was 5.8 mSv for this protocol which is 49.2% less than conventional Tc-99m studies and 75.7% less than conventional Tl-201/Tc-99m dual isotope studies. CONCLUSIONS: New SPECT camera technology with low isotope dose significantly reduces ionizing radiation exposure and imaging times compared to traditional protocols while maintaining image quality and diagnostic accuracy.

Comparison of high efficiency CZT SPECT MPI to coronary angiography.

BACKGROUND: The recently introduced cadmium zinc telluride (CZT) SPECT cameras have the potential to reduce radiation exposure to patients and shorten imaging time. So far, there has been only one small study comparing the results of high efficiency CZT SPECT myocardial perfusion imaging (MPI) to invasive coronary angiography. METHODS: All patients who had either a Tc-99m sestamibi or Tl-201 SPECT MPI study using a CZT camera (GE Discovery NM 530c) over a 1-year period followed by a coronary angiogram within 2 months were included. Only patients with a history of CABG surgery were excluded. Standard stress protocols were employed. Rest images were acquired for 5 min and stress supine and prone images for 3 min each. Both MPI studies and coronary angiograms were interpreted by blinded readers. A standard 17-segment model was employed for MPI interpretation, and coronary angiograms were interpreted for the presence of obstructive epicardial coronary artery disease (CAD) defined as ≥70% luminal narrowing. Correlation was based on the ability to diagnose obstructive epicardial CAD. RESULTS: Of the 3,111 patients who underwent SPECT imaging using the CZT camera during this time period, 230 patients qualified for the correlation study (mean age 64.2 ± 11.0 years old, 69% male, and 49% had a history of intracoronary stenting). Tc-99m was used in 76% vs Tl-201 in 24% of the studies. Exercise stress was performed in 60% of patients and vasodilator pharmacologic stress in 40%. Sensitivity was 95%, normalcy rate was 97%, and accuracy was 69% for detecting obstructive CAD. CONCLUSIONS: In this so far largest correlation study between coronary angiography and high efficiency CZT SPECT imaging, a high sensitivity and accuracy for detecting obstructive epicardial CAD was found for this new SPECT camera technology.