Prevalence of Iron Deficiency and Iron Deficiency Anemia in Strenuously Training Male Army Recruits.

OBJECTIVES: The objectives of our study were to determine the effect of strenuous physical training on the prevalence of iron deficiency anemia (IDA), iron deficiency (ID) with normal hemoglobin (Hb), and anemia without ID. METHODS: Our study was a prospective observational study. We followed 115 healthy male recruits in the Israel Defense Forces elite units during 15 months of training. Blood samples were collected at recruitment and at 6-, 9- and 15-month follow-ups. RESULTS: Upon recruitment, anemia (Hb < 14 g/dL), ID, and ID anemia (IDA) were diagnosed in 28, 31, and 9% of individuals, respectively. Sixty-three subjects (54%) were followed for 6 months; 9 of them (14%) developed new-onset IDA. Among them, the prevalence of anemia rose from 19 to 52%, and ID from 33 to 35%. At the 15-month follow-up, 29% had developed new-onset IDA and 65% showed evidence of ID. CONCLUSION: We report a high prevalence of anemia, ID, and IDA among young healthy males participating in prolonged strenuous training programs. These findings can be partly explained by the physiological changes associated with strenuous physical activity. Further investigations aiming to develop specific diagnostic guidelines for this unique population are warranted.

The added predictive role of echocardiography in patients with mild or moderate Coronavirus Disease 2019.

AIMS: Recently, several therapeutic agents have decreased the progression to critical disease in patients with mild/moderate COVID-19. However, their use is limited to patients with ≥1 clinical risk factor. We aimed to evaluate echocardiographic features that may aid in risk stratification for patients with mild/moderate COVID-19. METHODS: 278 consecutive patients with mild/moderate COVID-19 underwent prospective clinical and echocardiographic examination, ≤7 days of symptoms, as part of a predefined protocol. Analysis to identify echocardiographic predictors of outcome was performed. RESULTS: In the multivariable risk model, E/e', TAPSE, and pulmonary acceleration time (PAT) were associated with the composite outcome (p = 0.01, 0.005, 0.05, respectively). Stepwise analyses showed that the addition of echocardiography on top of having ≥1 clinical risk factor and even using each parameter separately improved the prediction of outcomes. If patients were re-categorized as high risk only if having both ≥1 clinical and ≥ 1 echocardiography risk parameter (E/e' > 8, TAPSE<1.8 cm, PAT<90 msec), or even one echo parameter separately, then specificity, positive predictive value, and accuracy improved. If patients were re-classified as high risk if having either ≥1 clinical risk factor or ≥ 1 high-risk echocardiography parameter, all five individuals who were missed by the ≥1 risk factor "rule", were correctly diagnosed as high risk. Similar analyses, including only patients with mild disease, showed that the addition of TAPSE improved the prediction of outcomes. CONCLUSIONS: In patients with mild/moderate COVID-19, a very limited echocardiographic exam is sufficient for improved outcome prediction, and may improve resource allocation for new anti-COVID-19 agents. TRANSLATIONAL ASPECT OF THE WORK: We show that among patients with mild/moderate COVID-19, several easily obtained echocardiographic findings are strongly correlated with mortality or progression to the need for invasive/non-invasive mechanical ventilation, even when adjusted for the presence or absence of ≥1 clinical risk factor. Furthermore, even a limited echocardiographic exam is sufficient to develop a strategy of risk stratification. We believe that our data have important implications for the clinicians involved in the acute treatment of patients with COVID-19.

Clustering of clinical and echocardiographic phenotypes of covid-19 patients.

We sought to divide COVID-19 patients into distinct phenotypical subgroups using echocardiography and clinical markers to elucidate the pathogenesis of the disease and its heterogeneous cardiac involvement. A total of 506 consecutive patients hospitalized with COVID-19 infection underwent complete evaluation, including echocardiography, at admission. A k-prototypes algorithm applied to patients' clinical and imaging data at admission partitioned the patients into four phenotypical clusters: Clusters 0 and 1 were younger and healthier, 2 and 3 were older with worse cardiac indexes, and clusters 1 and 3 had a stronger inflammatory response. The clusters manifested very distinct survival patterns (C-index for the Cox proportional hazard model 0.77), with survival best for cluster 0, intermediate for 1-2 and worst for 3. Interestingly, cluster 1 showed a harsher disease course than cluster 2 but with similar survival. Clusters obtained with echocardiography were more predictive of mortality than clusters obtained without echocardiography. Additionally, several echocardiography variables (E' lat, E' sept, E/e average) showed high discriminative power among the clusters. The results suggested that older infected males have a higher chance to deteriorate than older infected females. In conclusion, COVID-19 manifests differently for distinctive clusters of patients. These clusters reflect different disease manifestations and prognoses. Although including echocardiography improved the predictive power, its marginal contribution over clustering using clinical parameters only does not justify the burden of echocardiography data collection.

Janus Kinase V617F mutation in cigarette smokers.

The JAK2 V617F mutation is responsible for the constitutive activation of the erythropoietin receptor signaling pathway in most cases of polycythemia vera (PV). The mutation has also been described in healthy people. As smoking may result in secondary polycythemia, the goal of this trial was to examine the effect of smoking on the prevalence of the JAK2 mutation and its correlation to erythrocytosis. The study was case-control. Hospitalized smokers (n = 81) and nonsmokers (n = 61) were recruited. Serum was drawn for complete blood count, erythropoietin, ferritin and venous blood gases. JAK2 mutation was analyzed by highly sensitive allele-specific Quantitative Real Time PCR. The JAK2 mutation was found in 29/81 (35.8%) of smokers in comparison to only 9/61 (14.8%) of the control group (P = 0.007). The frequency of the mutation among smokers who were positive for the JAK2 mutation had a mean of 6.78 × 10(-4) ± 1.08 × 10(-3) vs. 1.51 × 10(-4) ± 2.04 × 10(-4) among nonsmokers (P = 0.027). Both frequencies are much lower than those found in PV. There was a medium correlation between older age and mutation frequency in nonsmokers (r= 0.67, P = 0.043). Hematocrit was higher in smokers (47.8 ± 6 vs. 41.7 ± 4.7, P < 0.0001), but no correlation was found to JAK2 mutation. In a cohort of hospitalized smokers and nonsmokers, JAK2 mutation was more prevalent and found in higher frequencies among smokers than nonsmokers. We suggest that accelerated erythropoiesis renders the cells susceptible to JAK2 mutation.

QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection.

Background: QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose: To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Materials and Methods: A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results: One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3-3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06-2.68, p = 0.027). Conclusion: Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

Pericardial Involvement in Patients Hospitalized With COVID-19: Prevalence, Associates, and Clinical Implications.

Background The scope of pericardial involvement in COVID-19 infection is unknown. We aimed to evaluate the prevalence, associates, and clinical impact of pericardial involvement in hospitalized patients with COVID-19. Methods and Results Consecutive patients with COVID-19 underwent clinical and echocardiographic examination, irrespective of clinical indication, within 48 hours as part of a prospective predefined protocol. Protocol included clinical symptoms and signs suggestive of pericarditis, calculation of modified early warning score, ECG and echocardiographic assessment for pericardial effusion, left and right ventricular systolic and diastolic function, and hemodynamics. We identified predictors of mortality and assessed the adjunctive value of pericardial effusion on top of clinical and echocardiographic parameters. The study included 530 patients. Pericardial effusion was found in 75 (14%), but only 17 patients (3.2%) fulfilled the criteria for acute pericarditis. Pericardial effusion was independently associated with modified early warning score, brain natriuretic peptide, and right ventricular function. It was associated with excess mortality (hazard ratio [HR], 2.44; P=0.0005) in nonadjusted analysis. In multivariate analysis adjusted for modified early warning score and echocardiographic and hemodynamic parameters, it was marginally associated with mortality (HR, 1.86; P=0.06) and improvement in the model fit (P=0.07). Combined assessment for pericardial effusion with modified early warning score, left ventricular ejection fraction, and tricuspid annular plane systolic excursion was an independent predictor of outcome (HR, 1.86; P=0.02) and improved model fit (P=0.02). Conclusions In hospitalized patients with COVID-19, pericardial effusion is prevalent, but rarely attributable to acute pericarditis. It is associated with myocardial dysfunction and mortality. A limited echocardiographic examination, including left ventricular ejection fraction, tricuspid annular plane systolic excursion, and assessment for pericardial effusion, can contribute to outcome prediction.

Immediate and early percutaneous coronary intervention in very high-risk and high-risk non-ST segment elevation myocardial infarction patients.

BACKGROUND: The European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (non-ST-segment elevation myocardial infarction [NSTEMI]) has recommended immediate (<2 h) percutaneous coronary intervention (PCI) in very-high risk patients and early (<24 h) PCI in high-risk patients. HYPOTHESIS: To examine the ESC NSTEMI guidelines adherence in a nationwide survey in Israel using the Acute Coronary Syndrome Israeli Survey (ACSIS). We hypothesized that adherence to the guidlines' recommnded PCI timing in NSTEMI pateints will be inadequate, partly due to the inconsistent evidence regarding its effect on clinical outcomes. METHODS: All NSTEMI patients who underwent PCI during the ACSIS surveys in 2016 and 2018 were included in the analysis. RESULTS: Out of 1793 NSTEMI patients, 1643 (92%) patients underwent PCI, and door to balloon time was documented in 1078 of them. One hundred and fifty-six (14.5%) patients and 922 (85.5%) patients were defined as very high-risk and high-risk NSTEMI patients, respectively. Of the very high-risk NSTEMI patients, only 10 (6.4%) underwent immediate coronary angiography, and 50 (32.1%) underwent early coronary angiography. Acute heart failure 139 (89.1%) was the main reason for including NSTEMI patients in the very high-risk category. Of the high-risk patients, early coronary angiography was performed in only 405 (43.9%) patients. Patients in whom coronary angiography was postponed were older and had more comorbidities. CONCLUSIONS: Despite guidelines recommendations for immediate and early PCI in very high-risk and high-risk NSTEMI patients, respectively, most patients do not undergo immediate or early PCI according to contemporary guidelines. Further studies are needed to better understand the reasons for guidelines' nonadherence in those high-risk patients.

A Contact-Free Optical Device for the Detection of Pulmonary Congestion-A Pilot Study.

BACKGROUND: The cost of heart failure hospitalizations in the US alone is over USD 10 billion per year. Over 4 million Americans are hospitalized every year due to heart failure (HF), with a median length of stay of 4 days and an in-hospital mortality rate that exceeds 5%. Hospitalizations of patients with HF can be prevented by early detection of lung congestion. Our study assessed a new contact-free optical medical device used for the early detection of lung congestion. METHODS: The Gili system is an FDA-cleared device used for measuring chest motion vibration data. Lung congestion in the study was assessed clinically and verified via two cardiologists. An algorithm was developed using machine learning techniques, and cross-validation of the findings was performed to estimate the accuracy of the algorithm. RESULTS: A total of 227 patients were recruited (101 cases vs. 126 controls). The sensitivity and specificity for the device in our study were 0.91 (95% CI: 0.86-0.93) and 0.91 (95% CI: 0.87-0.94), respectively. In all instances, the observed estimates of PPVs and NPVs were at least 0.82 and 0.90, respectively. The accuracy of the algorithm was not affected by different covariates (including respiratory or valvular conditions). CONCLUSIONS: This study demonstrates the efficacy of a contact-free optical device for detecting lung congestion. Further validation of the study results across a larger and precise scale is warranted.

A novel contact-free atrial fibrillation monitor: a pilot study.

Aims: Atrial fibrillation (AF) is a major cause of morbidity and mortality. Current guidelines support performing electrocardiogram (ECG) screenings to spot AF in high-risk patients. The purpose of this study was to validate a new algorithm aimed to identify AF in patients measured with a recent FDA-cleared contact-free optical device. Methods and results: Study participants were measured simultaneously using two devices: a contact-free optical system that measures chest motion vibrations (investigational device, 'Gili') and a standard reference bed-side ECG monitor (Mindray®). Each reference ECG was evaluated by two board certified cardiologists that defined each trace as: regular rhythm, AF, other irregular rhythm or indecipherable/missing. A total of 3582, 30-s intervals, pertaining to 444 patients (41.9% with a history of AF) were made available for analysis. Distribution of patients with active AF, other irregular rhythm, and regular rhythm was 16.9%, 29.5%, and 53.6% respectively. Following application of cross-validated machine learning approach, the observed sensitivity and specificity were 0.92 [95% confidence interval (CI): 0.91-0.93] and 0.96 (95% CI: 0.95-0.96), respectively. Conclusion: This study demonstrates for the first time the efficacy of a contact-free optical device for detecting AF.

Long-term Implications of Post-Procedural Left Ventricular End-Diastolic Pressure in Patients Undergoing Transcatheter Aortic Valve Implantation.

Current risk models have only limited accuracy in predicting transcatheter aortic valve Implantation (TAVI) outcomes and there is a paucity of clinical variables to guide patient management after the procedure. The prognostic impact of elevated left ventricular end-diastolic pressure (LVEDP) in TAVI patients is unknown. The aim of the present study was to evaluate the prognostic value of after-procedural LVEDP in patients who undewent TAVI. Consecutive patients with severe symptomatic aortic stenosis who undewent TAVI were divided into 2 groups according to after-procedural LVEDP above and below or equal 12 mm Hg. Collected data included baseline clinical, laboratory and echocardiographic variables. We evaluated the impact of elevated vs. normal LVEDP on in-hospital outcomes, short- and long-term mortality. Eight hundred forty-five patients were included in the study with complete in-hospital and late mortality data available for all survivors (median follow-up 29.5 months [IQR 16.5 to 48.0]). The mean age (±SD) was 82.3±6.2 years and mean Society of Thoracic Surgery score was 4.0%±3.0%. Patients with LVEDP>12 mm Hg (n = 591, 70%) and LVEDP≤12 mm Hg (n = 254, 30%) had a 6-months mortality rate of 6.8% and 2%, respectively (P=0.004) and a 1-year mortality rate of 10.1% vs 4.9%, respectively (p = 0.017). By multivariable analysis, after-procedural LVEDP>12 mm Hg was independently associated with all-cause mortality (HR 2.45, 95% CI 1.58 to 3.76, p <0.001) during long-term follow-up. In conclusion, elevated after-procedural LVEDP in patients who undewent TAVI is an independent predictor of mortality following TAVI. Further research regarding the use of LVEDP as a tool for after-procedural medical management is warranted.

Risk prediction in patients with COVID-19 based on haemodynamic assessment of left and right ventricular function.

AIMS: Cardiovascular involvement is common in COVID-19. We sought to describe the haemodynamic profiles of hospitalized COVID-19 patients and determine their association with mortality. METHODS AND RESULTS: Consecutive hospitalized patients diagnosed with COVID-19 infection underwent clinical evaluation using the Modified Early Warning Score (MEWS) and a full non-invasive echocardiographic haemodynamic evaluation, irrespective of clinical indication, as part of a prospective predefined protocol. Patients were stratified based on filling pressure and output into four groups. Multivariable Cox-Hazard analyses determined the association between haemodynamic parameters with mortality. Among 531 consecutive patients, 44% of patients had normal left ventricular (LV) and right ventricular (RV) haemodynamic status. In contrast to LV haemodynamic parameters, RV parameters worsened with higher MEWS stage. While RV parameters did not have incremental risk prediction value above MEWS, LV stroke volume index, E/e' ratio, and LV stroke work index were all independent predictors of outcome, particularly in severe disease. Patients with LV or RV with high filling pressure and low output had the worse outcome, and patients with normal haemodynamics had the best (P < 0.0001). CONCLUSION: In hospitalized patients with COVID-19, almost half have normal left and right haemodynamics at presentation. RV but not LV haemodynamics are related to easily obtainable clinical parameters. LV but not RV haemodynamics are independent predictors of mortality, mostly in patients with severe disease.

The Predictive Role of Combined Cardiac and Lung Ultrasound in Coronavirus Disease 2019.

BACKGROUND: The aim of this study was to evaluate sonographic features that may aid in risk stratification and to propose a focused cardiac and lung ultrasound (LUS) algorithm in patients with coronavirus disease 2019. METHODS: Two hundred consecutive hospitalized patients with coronavirus disease 2019 underwent comprehensive clinical and echocardiographic examination, as well as LUS, irrespective of clinical indication, within 24 hours of admission as part of a prospective predefined protocol. Assessment included calculation of the modified early warning score (MEWS), left ventricular systolic and diastolic function, hemodynamic and right ventricular assessment, and a calculated LUS score. Outcome analysis was performed to identify echocardiographic and LUS predictors of mortality or the composite event of mortality or need for invasive mechanical ventilation and to assess their adjunctive value on top of clinical parameters and MEWS. RESULTS: A simplified echocardiographic risk score composed of left ventricular ejection fraction < 50% combined with tricuspid annular plane systolic excursion < 18 mm was associated with mortality (P = .0002) and with the composite event (P = .0001). Stepwise analyses evaluating echocardiographic and LUS parameters on top of existing clinical risk scores showed that addition of tricuspid annular plane systolic excursion and stroke volume index improved prediction of mortality when added to clinical variables but not when added to MEWS. Once echocardiography was added, and patients were recategorized as high risk only if having both high-risk MEWS and high-risk cardiac features, specificity increased from 63% to 87%, positive predictive value from 28% to 48%, and accuracy from 66% to 85%. Although LUS was not associated with incremental risk prediction for mortality above clinical and echocardiographic criteria, it improved prediction of need for invasive mechanical ventilation. CONCLUSIONS: In hospitalized patients with coronavirus disease 2019, a very limited echocardiographic examination is sufficient for outcome prediction. The addition of echocardiography in patients with high-risk MEWS decreases the rate of falsely identifying patients as high risk to die and may improve resource allocation in case of high patient load.

COVID-19, a tale of two peaks: patients' characteristics, treatments, and clinical outcomes.

Coronavirus 2019 disease (COVID-19) continues to challenge healthcare systems globally as many countries are currently experiencing an increase in the morbidity and mortality. Compare baseline characteristics, clinical presentation, treatments, and clinical outcomes of patients admitted during the second peak to those admitted during the first peak. Retrospective analysis of 258 COVID-19 patients consecutively admitted to the Tel Aviv Medical Center, of which, 131 during the first peak (March 21-May 30, 2020) and 127 during the second peak (May 31-July 16, 2020). First and second peak patients did not differ in baseline characteristics and clinical presentation at admission. Treatment with dexamethasone, full-dose anticoagulation, tocilizumab, remdesivir, and convalescent plasma transfusion were significantly more frequent during the second peak, as well as regimens combining 3-4 COVID-19-directed drugs. Compared to the first peak, 30-day mortality and invasive mechanical ventilation rates as well as adjusted risk were significantly lower during the second peak (10.2%, vs 19.8% vs p = 0.028, adjusted HR 0.39, 95% CI 0.19-0.79, p = 0.009 and 8.8% vs 19.3%, p = 0.002, adjusted HR 0.29, 95% CI 0.13-0.64, p = 0.002; respectively). Rates of 30-day mortality and invasive mechanical ventilation, as well as adjusted risks, were lower in the second peak of the COVID-19 pandemic among hospitalized patients. The change in treatment strategy and the experienced gained during the first peak may have contributed to the improved outcomes.

Clinical Presentation of Sustained Monomorphic Ventricular Tachycardia Without Cardiac Arrest.

Background "Palpitations" are one of the most common complaints prompting medical attention. Textbooks of medicine and cardiology as well as guideline documents and position papers describe palpitations as a common symptom of ventricular tachycardia (VT). However, data to support this description are lacking. The aim of our study was to evaluate the symptomatology of sustained monomorphic VT with emphasis on the prevalence of palpitations. Methods and Results Consecutive patients presenting to our center with a first event of a regular sustained monomorphic VT (n=59) or a regular supraventricular tachycardia (SVT; n=109) between January 2012 and September 2019 were interviewed regarding their symptoms during the arrhythmic event. We included only patients with a first arrhythmic event to avoid the influence of previous medical encounters on our patients' terminology. As expected, patients with VT were older (age 68.8±13.6 versus 52.6±16.8 years; P<0.001), more often of male sex (94.9% versus 37.6%; P<0.001), had lower left ventricular ejection fraction (37±11% versus 59±2%, P<0.001) and more comorbidities (87.6% versus 40.5%; P<0.001) compared with patients with SVT. Importantly, even though the heart rate upon presentation did not differ between the 2 groups (165±26 beats/min during VT versus 171±32 beats/min during SVT; P=0.16), symptomatology differed significantly; specifically, palpitations were reported in only 8.8% of VT patients, compared with 90.7% of SVT patients (P<0.001). Common symptoms in the VT group included chest pain (64%), dyspnea (21%), and dizziness (26%). Conclusions Despite similar heart rate, patients with VT rarely report having palpitations, whereas patients with SVT do so commonly. This finding may assist with decision making in patients reporting palpitations in whom an ECG tracing is not available.

Pulmonary embolism: Care standards in 2018.

Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Clinical presentation can be diverse, and clinicians should have a high index of suspicion regarding the diagnosis. Evaluation should include detailed history of possible risk factors, physical examination and laboratory tests that would support the diagnosis and help risk-stratify patients. Finally, a dedicated imaging study should be performed in order to make a definitive diagnosis. Decisions regarding short-term, immediate, treatment are dictated by PE risk category. Treatment of low and high-risk PE is relatively straightforward. But treating moderate risk PE is challenging since aggressive treatment is not devoid of potential harm. This review focuses on the acute and chronic treatment of PE. We present risk stratification, guidance as to treatment choice and insights into chronic treatment with available anticoagulants.