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.

Multimodality cardiac imaging for management of a cardiac mass in the era of COVID-19: a case report.

BACKGROUND: Atrial myxomas are the most common benign cardiac tumours. This case highlights an unusual presentation and complex management of a patient who was incidentally found to have a left atrial tumour concerning for a myxoma. CASE SUMMARY: A 54-year-old-woman presented with symptoms of nausea and vomiting and was found to have a left atrial mass incidentally in addition to a renal infarct. She was also found to have COVID-19 and the mass was initially thought to be a thrombus. With the help of multimodality imaging, it was determined that the mass was an atrial myxoma and she was started on short-term anticoagulation to prevent recurrent embolization. After 6 weeks of anticoagulation, she successfully underwent elective resection of the mass which was confirmed to be myxoma with superimposed thrombus. DISCUSSION: It is difficult to differentiate cardiac tumours from intracardiac thrombus and multimodality cardiac imaging is crucial to make an accurate diagnosis. While the treatment of atrial myxomas involves early surgical resection, it becomes more complicated with concurrent COVID-19 infection.

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.

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.

Reduction in occupational and patient radiation exposure from myocardial perfusion imaging: impact of stress-only imaging and high-efficiency SPECT camera technology.

UNLABELLED: Recently introduced high-efficiency SPECT cameras have demonstrated the ability to reduce radiation exposure to patients undergoing myocardial perfusion imaging studies, especially when combined with stress-only imaging protocols. To date there have been no relevant studies examining the reduced occupational radiation exposure to medical staff. We sought to determine whether changes in stress myocardial perfusion imaging protocols and camera technology can reduce the occupational radiation exposure to the staff of a nuclear cardiology laboratory. METHODS: Monthly radiation dosimeter readings from 4 nuclear technologists, 4 nurses, and 2 administrative employees were analyzed from two 12-mo periods: October 2007-September 2008 (period 1), before the use of high-efficiency SPECT, and October 2010-September 2011 (period 2), after high-efficiency SPECT was introduced. The average monthly dose equivalent in millirems (1 mrem = 0.01 mSv) was recorded from personal dosimeters worn on laboratory coats. The total activity of (99m)Tc used per month, mean (99m)Tc administered activity per patient, average number of patients per month, patient time spent in the laboratory, and proportion of stress-only studies were determined. RESULTS: There were 3,539 patients in period 1 and 3,898 in period 2. An approximately 40% reduction in the dose equivalent across all staff members occurred during this time (-16.9 and -16.2 mrem for nuclear technologists and nurses, respectively; P < 0.0001). During period 2, the total activity of (99m)Tc used per month decreased (10,746 vs. 7,174 mCi [1 mCi = 37 MBq], P < 0.0001), as did the mean (99m)Tc administered activity per patient (36.5 vs. 23.8 mCi, P < 0.0001). The percentage of patients having stress-only imaging increased (35% vs. 56%, P < 0.0001), and the total patient time spent in the laboratory decreased. Radiation dose equivalent levels were reduced in period 2 to 1%-7% of the allowed annual occupational dose equivalent. The combination of the use of high-efficiency SPECT technology and stress-only protocols resulted in a 34.7% reduction in mean total (99m)Tc administered activity between time periods, with camera technology being responsible for 39.2% of the reduction and stress-only protocols for 60.8%. CONCLUSION: A combination of high-efficiency SPECT technology and selective use of stress-only protocols significantly reduces the occupational radiation dose equivalent to the staff of a nuclear cardiology laboratory.

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.

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.

Comparison of the results of aortic valve replacement with or without concomitant coronary artery bypass grafting in patients with left ventricular ejection fraction < or =30% versus patients with ejection fraction >30%.

The present study was designed to test the hypothesis that low-ejection fraction (EF), low-gradient aortic stenosis (AS) is a predictor of major morbidity after aortic valve replacement (AVR). We retrospectively analyzed prospectively collected data from 597 consecutive patients with AS (mean age 72 +/- 11 years) who had undergone AVR or combined AVR and coronary artery bypass grafting (CABG) from 1998 to 2006 (EF < or =30% in 73 [12%]). The outcome measures included hospital mortality, major complications, and long-term survival. The overall hospital mortality rate was 4% (low-EF AS 5%; low-EF AS plus CABG 8%; AS controls 4%; AS plus CABG controls 3%; p = 0.42). Low-EF, low-gradient AS was not an independent risk factor for hospital mortality but predicted stroke (odds ratio [OR] 4.3), deep sternal wound infection (OR 10.0), sepsis (OR 6.8), gastrointestinal complications (OR 4.2), and respiratory failure (OR 4.4). The survival rate at 1, 3, and 5 years was 69 +/- 8%, 69 +/- 8%, and 65 +/- 8% in the low-EF, low-gradient, AVR plus CABG group and 95 +/- 4%, 92 +/- 5%, and 82 +/- 7% in the low-EF, low-gradient AVR group compared to 93 +/- 2%, 88 +/- 2%, and 78 +/- 3% in the AVR plus CABG control group and 93 +/- 2%, 89 +/- 2%, and 85 +/- 3% in the AVR control group (p = 0.001), respectively. In the patients with low-EF AS who experienced major postoperative morbidity, the 1-year survival rate was significantly reduced (54 +/- 14%) compared to those who did not (95 +/- 3%, p <0.001). In conclusion, low-EF, low-gradient AS is a predictor of increased major morbidity after AVR, which nonetheless remains the treatment of choice for most patients because of the excellent early and late survival. However, patients with strong risk factors for postoperative renal and respiratory failure might derive less benefit from conventional surgical AVR.

SPECT myocardial perfusion imaging in morbidly obese patients: image quality, hemodynamic response to pharmacologic stress, and diagnostic and prognostic value.

BACKGROUND: Obesity is a growing epidemic in the United States, and little is known about the characteristics of the morbidly obese population (body mass index [BMI] > or = 40 kg/m2) undergoing stress myocardial perfusion imaging (MPI). METHODS AND RESULTS: We retrospectively reviewed all consecutive morbidly obese patients without known coronary artery disease presenting for a clinically indicated technetium 99m (Tc-99m) gated stress single photon emission computed tomography imaging study over a 42-month period. Studies were analyzed for image quality, for the contribution of attenuation correction to image interpretation, and for the hemodynamic response to pharmacologic stress. In patients who subsequently had cardiac catheterization, the results were compared with those from the initial MPI study, and the Social Security Death Index and hospital medical records were searched to the assess survival rate in the entire cohort. A total of 433 patients were identified with a mean BMI of 47.3 +/- 8 kg/m2 and a mean Tc-99m stress dose of 35.6 +/- 5.4 mCi. Image quality was good in 61% of the patients, adequate in 37%, and poor in 2%. It was found to be dependent on the stressor used (better with exercise) but did not correlate with increasing weight or BMI. Attenuation correction was used in 95% of the studies reviewed and was helpful for image interpretation in 60%. The heart rate response to dipyridamole and adenosine was more pronounced and the blood pressure response to dipyridamole was less pronounced in morbidly obese patients compared with nonobese control patients. In the 43 patients who underwent catheterization, stress MPI had a sensitivity of 95% and negative predictive value of 80%. Kaplan-Meier survival analysis at 1 year showed a significant difference in survival rate of 98.3% for normal MPI studies and 94.0% for abnormal MPI studies (P = .02). CONCLUSION: Diagnostic-quality single photon emission computed tomography imaging is feasible in the majority (98%) of morbidly obese patients with the use of a dual-head camera, attenuation correction, and high stress Tc-99m tracer doses. Exercise stress was associated with better image quality. The prognostic value of a normal MPI study in this population appears to be less favorable than in non-morbidly obese patients.

Calcific aortic stenosis: new pathophysiologic insights and possible new medical therapy.

Aortic stenosis is a progressive disease of aging with serious complications. A common disease of the elderly, it may inexorably progress to stenosis. Recent retrospective studies have correlated risk factors commonly associated with coronary and vascular atherosclerosis with an accelerated rate of aortic valve stenosis. Although hydroxymethyl glutaryl co-enzyme A reductase inhibitor (statin) treatment therapy has been shown to delay the rate of progression of valvular aortic stenosis, the salutary mechanism of the statin may be cholesterol-lowering and/or anti-inflammatory. Further prospective studies are warranted to investigate the mechanism and medical therapy of aortic sclerosis and stenosis.

Effect of hormone replacement therapy on the electrocardiographic response to exercise.

BACKGROUND: Female gender and hormonal status affect electrocardiographic (ECG) response to exercise. Both are often cited as factors contributing to the decreased diagnostic accuracy of exercise stress tests in women. However, there is a paucity of data. To explore the relationship between hormonal status and exercise-induced ECG changes, we used gated single photon emission computed tomography (SPECT) technetium 99m sestamibi imaging for detection of myocardial ischemia. METHODS AND RESULTS: ECG response to exercise was analyzed in all female patients who underwent symptom-limited exercise stress testing over a 12-month period with no evidence of ischemia on SPECT myocardial perfusion imaging (N = 404). Hormonal status was defined as premenopausal (n = 78), postmenopausal (n = 277), and postmenopausal on hormone replacement therapy (HRT) (n = 49). Positive ECG response for ischemia was defined as 1 mm or greater horizontal and/or downsloping ST depression during and/or after exercise. The frequency of a positive ECG response to exercise without evidence of ischemia on gated SPECT imaging was analyzed according to hormonal status. Seventeen of 78 premenopausal women (22%), 48 of 277 postmenopausal women (17%), and 19 of 49 women taking HRT (39%) had a positive ECG response. ECG positivity was significantly higher in HRT users when compared with premenopausal (P =.05) and postmenopausal women (P =.001). CONCLUSIONS: Exogenous estrogen replacement therapy affects ST-segment response to exercise, likely through a nonischemic mechanism. Unless HRT can be discontinued for a prolonged period of time (up to 6 weeks) prior to a stress test, myocardial imaging should be used to improve diagnostic accuracy.