Acute Coronary Syndrome During the Era of COVID-19: Perspective and Implications Using Google Trends.

Background: Acute coronary syndrome (ACS) hospital admissions decreased during the start of the COVID-19 outbreak. Information is limited on how Google searches were related to patients' behaviour during this time. Methods: We examined de-identified data from 2019 through 2020 regarding the following monthly items: (i) admissions for ACS from the Veterans Affairs Healthcare System; (ii) out-of-hospital cardiac arrest (OHCA) from the National Emergency Medical Services Information System (NEMSIS) public dataset; and (iii) Google searches for "chest pain," "coronavirus," "chest pressure," and "hospital safe" from Google Trends. We analyzed the trends for ACS admissions, OHCA, and Google searches. Results: During the early months of the first COVID-19 outbreak, the following occurred: (i) Veterans Affairs data showed a significant reduction in ACS admissions at a national and regional (Florida) level; (ii) the NEMSIS database showed a marked increase in OHCA at a national level; and (iii) Google Trends showed a significant increase in the before-mentioned Google searches at a national and regional level. Conclusions: ACS hospital admissions decreased during the beginning of the pandemic, likely owing to delayed healthcare utilization secondary to patients fear of acquiring a COVID-19 infection. Concordantly, the volume of Google searches for hospital safety and ACS symptoms increased, along with OHCA events, during the same time. Our results suggest that Google Trends may be a useful tool to predict patients' behaviour and increase preparedness for future events, but statistical strategies to establish association are needed.

Contexte: Les admissions à l'hôpital pour un syndrome coronarien aigu (SCA) ont diminué au début de la pandémie de COVID-19. Or, il existe peu de données sur les recherches effectuées par les patients dans Google pendant cette période. Méthodologie: Nous avons examiné des données mensuelles dépersonnalisées de 2019 à 2020 sur les éléments suivants : i) admissions pour un SCA dans le système de santé de Veterans Affairs aux États-Unis; ii) arrêts cardiaques extrahospitaliers (ACEH) de l'ensemble de données publiques du National Emergency Medical Services Information System (NEMSIS); et iii) les recherches dans Google selon Google Trends pour « chest pain ¼ (douleur thoracique), « coronavirus ¼, « chest pressure ¼ (oppression thoracique) et « hospital safe ¼ (sécurité dans les hôpitaux). Nous avons également analysé les tendances relatives aux admissions pour un SCA, aux ACEH et aux recherches dans Google. Résultats: Pour les premiers mois de la première vague de COVID-19, les observations sont les suivantes : i) les données de Veterans Affairs ont montré une réduction significative des admissions pour un SCA à l'échelle nationale et régionale (Floride); ii) la base de données du NEMSIS a montré une augmentation marquée des ACEH à l'échelle nationale; et iii) les tendances observées au moyen de Google Trends indiquent une augmentation significative à l'échelle nationale et régionale des recherches dans Google à l'aide des termes mentionnés précédemment. Conclusions: Les admissions à l'hôpital pour un SCA ont diminué au début de la pandémie, probablement en raison de la crainte des patients de contracter la COVID-19, qui les a amenés à repousser le recours à des soins de santé. Pendant la même période, le volume des recherches dans Google à propos de la sécurité dans les hôpitaux et les symptômes de SCA a augmenté, tout comme le nombre d'ACEH. Nos résultats semblent indiquer que Google Trends pourrait être un outil pratique pour prédire les comportements des patients et mieux se préparer aux événements futurs, mais il convient d'élaborer des stratégies statistiques permettant de mieux caractériser ces liens.

Extracellular Vesicles as Delivery Systems in Disease Therapy.

Extracellular vesicles (EVs)/exosomes are nanosized membrane-bound structures that are released by virtually all cells. EVs have attracted great attention in the scientific community since the discovery of their roles in cell-to-cell communication. EVs' enclosed structure protects bioactive molecules from degradation in the extracellular space and targets specific tissues according to the topography of membrane proteins. Upon absorption by recipient cells, EV cargo can modify the transcription machinery and alter the cellular functions of these cells, playing a role in disease pathogenesis. EVs have been tested as the delivery system for the mRNA COVID-19 vaccine. Recently, different therapeutic strategies have been designed to use EVs as a delivery system for microRNAs and mRNA. In this review, we will focus on the exciting and various platforms related to using EVs as delivery vehicles, mainly in gene editing using CRISPR/Cas9, cancer therapy, drug delivery, and vaccines. We will also touch upon their roles in disease pathogenesis.

The CHA2DS2-VASc Score for Risk Stratification of Stroke in Heart Failure With-vs-Without Atrial Fibrillation.

A recent study suggested that the CHA2DS2-VASc score can risk stratify heart failure (HF) patients without atrial fibrillation (AF) for stroke. We performed a retrospective analysis using the national Veteran Affairs database to externally validate the findings. Crude incidence rates of end points were calculated. A Cox proportional model was used to study the association between the CHA2DS2-VASc score and outcomes. In HF patients with AF (n = 17,481) and without AF (n = 36,935), the 1 year incidence rate for ischemic stroke, thromboembolism, thromboembolism (without MI), and death were 2.7 and 2.0%; 10.3 and 7.9%; 4.1 and 3.1%; and 19.2 and 26.0%, respectively, with higher rates with increasing CHA2DS2-VASc scores both with and without AF. CHA2DS2-VASc score predicted strokes in HF patients without AF (1-year C-statistic 0.62, 95% CI 0.60-0.64; NPV 85.4%, 95% CI 83.4-87.4%) with similar predictive ability to those with AF (C-statistic 0.59, 95% CI 0.56-0.62; NPV 86.4%, 95% CI 82.6-90.2%). Among patients with HF, there was an increased risk of stroke, thromboembolism, and death with increasing CHA2DS2-VASc scores regardless of AF status. Our findings support the use of the CHA2DS2-VASc score as a prognostic tool in HF.

The association between in-hospital hemoglobin changes, cardiovascular events, and mortality in acute decompensated heart failure: Results from the ESCAPE trial.

INTRODUCTION: The effect of acute changes of hemoglobin during index heart failure admission on long-term outcomes remains unknown. METHODS: We examined 433 patients enrolled in the ESCAPE trial. RESULTS: Of the 433 patients, 324 (75%) had baseline and discharge hemoglobin available for analysis. Of those, 64 (20%) had at least 1g/dL drop of hemoglobin by time of discharge. Compared to patients without hemoglobin changes (g/dL), patients with hemoglobin drop were older (59 vs. 55, p=0.011), had lower systolic BP (mmHg) (99 vs. 106, p=0.017), lower sodium (mg/dL) (136 vs. 137 (mg/dL), p=0.025), higher BUN (mg/dL) (37 vs. 26, p<0.001), higher creatinine (mg/dL) (1.6 vs. 1.3, p<0.001) and higher hospital length of stay (10days vs. 6days, p=<0.001). Higher hemoglobin drop was observed in the pulmonary artery catheter (PACs) (vs. clinical care) randomized arm of the trial (2g/dL: 10% versus 3%, p=0.010; 3g/dL: 5% versus 0%, p=0.005). After adjustments, a drop of hemoglobin with at least 1g/dL was associated with increased mortality risk (Adjusted HR 2.38, p=0.003) and higher hemoglobin concentrations by the time of discharge was associated with lower mortality rate (Adjusted HR 0.79, p=0.003). PACs insertion was not associated with adverse clinical outcomes by quartiles of % change of hemoglobin. However, PACs use was an independent predictor of hemoglobin drop during heart failure admission (Adjusted OR: Hb Drop 1g/dL: 1.88, p=0.043; Hb Drop 2g/dL: 3.6 p=0.025). CONCLUSION: In-hospital decrease in hemoglobin is independently associated with increased long-term mortality and hospital length of stay in ADHF. The ideal hemoglobin levels in ADHF patients should be investigated and the insertion of PACs to direct therapy should be weighed against bleeding risks.

New-onset versus prior history of atrial fibrillation: Outcomes from the AFFIRM trial.

BACKGROUND: There are limited data on prognosis and outcomes of patients with new-onset atrial fibrillation (AF) compared with those with a prior history of AF. METHODS AND RESULTS: We conducted a comparison of these 2 groups in the AFFIRM trial. New-onset AF was the qualifying arrhythmia in 1,391 patients (34%). Compared with patients with prior history of AF, patients with new-onset AF were more likely to have a history of heart failure. There was no mortality difference between rate control (RaC) and rhythm control (RhC) among patients with new-onset AF (17% vs 20%, P = .152). In the univariate model, new-onset AF was associated with increased risk of mortality compared with history of prior AF (RaC unadjusted hazard ratio [HR] 1.36 [P = .010], RhC unadjusted HR 1.39 [P = .003]). However, after multivariate adjustments, new-onset AF did not carry an increased risk of mortality (RaC adjusted HR 1.14 [P = .370], RhC adjusted HR 1.16 [P = .248]). Subjects with new-onset AF randomized to the RhC arm were more likely to remain in normal sinus rhythm at follow-up (adjusted HR 0.79, P = .012) compared with patients with prior history of AF. CONCLUSIONS: In a multivariable analysis adjusting for confounders, new-onset AF was not associated with increased mortality compared with prior history of AF regardless of the treatment strategy. Patients with new-onset AF treated with the rhythm control strategy were more likely to remain in normal sinus rhythm on follow-up.

Association between anti-human heat shock protein-60 and interleukin-2 with coronary artery calcium score.

INTRODUCTION: Based upon evidence suggesting that concentrations of anti-heat shock protein-60 (anti-HSP60) and interleukin-2 (IL-2) are associated with atherogenesis, we tested the hypothesis that anti-HSP60 and IL-2 are associated with coronary artery calcium (CAC) score, a marker of subclinical atherosclerosis. METHODS: We evaluated 998 asymptomatic adults, age 45-84 years, without known coronary disease from the Multi-Ethnic Study of Atherosclerosis (MESA), who had anti-HSP60 measured at baseline. Tertiles of serum anti-HSP60 were evaluated. The associations of IL-2 and anti-HSP60 with CAC were assessed using multivariate analyses, with adjustments for coronary risk factors and Framingham risk score. RESULTS: Patients' demographics, diabetes, hypertension, obesity, or dyslipidaemia did not show differences in levels of anti-HSP60. The median (IQR) Framingham risk score was 11 (5-22), 8 (5-16), and 9 (5-18) for the first, second, and third tertiles, respectively (p=0.043). IL-2 and tumour necrosis factor α (TNF-α) were associated with increased CAC (IL-2: OR 3.70, p<0.001; TNF-α: OR 4.63, p<0.001). In multivariate regression, the highest tertiles of anti-HSP60 and IL-2 were associated with increased risk of CAC (HSP60 T3: OR 1.49, p=0.022; IL-2: OR 2.49, p<0.001). After adjustment, significant progression of CAC was observed in patients with higher baseline levels of anti-HSP60 (estimate 31.73, p=0.016) and IL-2 (estimate 34.39, p=0.024). CONCLUSIONS: Increased concentrations of inflammatory markers (IL-2 and anti-HSP60) are associated with an increased CAC at baseline and follow-up in healthy asymptomatic adults. Future studies should be carried out to assess its association with early development of atherosclerosis.

Hepatocellular carcinoma to the right ventricle.

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer in the world, but metastatic disease to the heart is rare. We present a case of a 63-year-old man with history of hepatitis C and cirrhosis, which had progressed to HCC. The patient had undergone two prior liver transplantations. He presented to the hospital complaining of worsening lower extremity edema. His exam was also pertinent for jugular venous distension, a 3/6 crescendo-decrescendo murmur, and hepatosplenomegaly. A transthoracic echocardiogram showed a large irregular lobulated mass in the apex of the right ventricle with a mobile pedunculated component. An MRI of the heart revealed a 4.4 × 3.4 × 4.0 cm mass within the right ventricular apex, which was subsequently biopsied and found to be moderately differentiated HCC with myocardial fragments. The patient opted out of any further therapy, or intervention, and was enrolled in hospice care.

Optimal blood pressure in patients with atrial fibrillation (from the AFFIRM Trial).

Many medications used to treat atrial fibrillation (AF) also reduce blood pressure (BP). The relation between BP and mortality is unclear in patients with AF. We performed a post hoc analysis of 3,947 participants from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management trial. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline and follow-up were categorized by 10-mm Hg increments. The end points were all-cause mortality (ACM) and secondary outcome (combination of ACM, ventricular tachycardia and/or fibrillation, pulseless electrical activity, significant bradycardia, stroke, major bleeding, myocardial infarction, and pulmonary embolism). SBP and DBP followed a "U-shaped" curve with respect to primary and secondary outcomes after multivariate analysis. A nonlinear Cox proportional hazards model showed that the incidence of ACM was lowest at 140/78 mm Hg. Subgroup analyses revealed similar U-shaped curves. There was an increased ACM observed with BP <110/60 mm Hg (hazard ratio 2.4, p <0.01, respectively, for SBP and DBP). In conclusion, in patients with AF, U-shaped relation existed between BP and ACM. These data suggest that the optimal BP target in patients with AF may be greater than the general population and that pharmacologic therapy to treat AF may be associated with ACM or adverse events if BP is reduced to <110/60 mm Hg.

ST-T wave abnormality in lead aVR and reclassification of cardiovascular risk (from the National Health and Nutrition Examination Survey-III).

Electrocardiographic lead aVR is often ignored in clinical practice. The aim of this study was to investigate whether ST-T wave amplitude in lead aVR predicts cardiovascular (CV) mortality and if this variable adds value to a traditional risk prediction model. A total of 7,928 participants enrolled in the National Health and Nutrition Examination Survey (NHANES) III with electrocardiographic data available were included. Each participant had 13.5 ± 3.8 years of follow-up. The study sample was stratified according to ST-segment amplitude and T-wave amplitude in lead aVR. ST-segment elevation (>8 µV) in lead aVR was predictive of CV mortality in the multivariate analysis when not accounting for T-wave amplitude. The finding lost significance after including T-wave amplitude in the model. A positive T wave in lead aVR (>0 mV) was the strongest multivariate predictor of CV mortality (hazard ratio 3.37, p <0.01). The addition of T-wave amplitude in lead aVR to the Framingham risk score led to a net reclassification improvement of 2.7% of subjects with CV events and 2.3% of subjects with no events (p <0.01). Furthermore, in the intermediate-risk category, 20.0% of the subjects in the CV event group and 9.1% of subjects in the no-event group were appropriately reclassified. The absolute integrated discrimination improvement was 0.012 (p <0.01), and the relative integrated discrimination improvement was 11%. In conclusion, T-wave amplitude in lead aVR independently predicts CV mortality in a cross-sectional United States population. Adding T-wave abnormalities in lead aVR to the Framingham risk score improves model discrimination and calibration with better reclassification of intermediate-risk subjects.

Electrocardiographic abnormalities and reclassification of cardiovascular risk: insights from NHANES-III.

BACKGROUND: We aimed to assess the additive value of electrocardiogram (ECG) findings to risk prediction models for cardiovascular disease. METHODS: Our dataset consisted of 6025 individuals with ECG data available from the National Health and Nutrition Examination Survey-III. This is a self-weighting sample with a follow-up of 79,046.84 person-years. The primary outcomes were cardiovascular mortality and all-cause mortality. We compared 2 models: Framingham Risk Score (FRS) covariates (Model A) and ECG abnormalities added to Model A (Model B), and calculated the net reclassification improvement index (NRI). RESULTS: Mean age of our study population was 58.7 years; 45.6% were male and 91.7% were white. At baseline, 54.6% of individuals had ECG abnormalities, of which 545 (9%) died secondary to a cardiovascular event, compared with 194 individuals (3.2%) (P <.01) without ECG abnormalities. ECG abnormalities were significant predictors of cardiovascular mortality after adjusting for traditional cardiovascular risk factors (hazard ratio 1.44; 95% confidence interval, 1.13-1.83). Addition of ECG abnormalities led to an overall NRI of 3.6% subjects (P <.001) and 13.24% in the intermediate risk category. The absolute integrated discrimination index was 0.0001 (P <.001). CONCLUSION: Electrocardiographic abnormalities are independent predictors of cardiovascular mortality, and their addition to the FRS improves model discrimination and calibration. Further studies are needed to assess the prospective application of ECG abnormalities in cardiovascular risk prediction in individual subjects.

Isolated nonspecific ST-segment and T-wave abnormalities in a cross-sectional United States population and Mortality (from NHANES III).

Most clinicians regard isolated, minor, or nonspecific ST-segment and T-wave (NS-STT) abnormalities to be incidental, often transient, and benign findings in asymptomatic patients. We sought to evaluate whether isolated NS-STT abnormalities on routine electrocardiograms (ECGs) are associated with increased risk of cardiovascular mortality (CM) and all-cause mortality (AM) in a cross-sectional United States population without known coronary artery disease. We included all adults 40 to 90 years of age without known coronary artery disease or risk equivalent based on history and laboratory values, enrolled in the NHANES III from 1988 to 1994, with electrocardiographic data available, and a total follow-up period of 59,781.75 patient-years. NS-STT abnormalities were defined by Minnesota Coding. Subjects were excluded if their mortality data were missing or if they had major electrocardiographic abnormalities, heart rate >120 beats/min, nonsinus rhythm, cardiac infarction/injury score ≥ 20 on ECG, left ventricular hypertrophy by Minnesota Codes 3.1 and 3.3, or patient-reported history coronary artery disease, congestive heart failure, stroke, diabetes, or peripheral arterial disease. The remaining 4,426 subjects were stratified by presence or absence of NS-STT abnormalities. Mortality was judged based on International Classification of Diseases, Tenth Revision coding linked to the National Death Index. Cox proportional hazard ratio was used for multivariate analysis, showing that CM (hazards ratio 1.71, 95% confidence interval 1.04 to 2.83, p = 0.04) and AM (hazards ratio 1.37, 95% confidence interval 1.03 to 1.81, p = 0.02) were significantly higher in the isolated NS-STT abnormalities group. In conclusion, isolated NS-STT abnormalities on ECG were associated with a higher incidence of CM and AM in this large nationally representative cross-sectional cohort without known coronary artery disease or coronary artery disease risk equivalents.

Pseudo-pulmonic stenosis in non-hodgkin's large B-cell lymphoma.

There have only been a few cases reported of right ventricular outflow tract obstruction secondary to diffuse large B-cell lymphomas. Mediastinal masses rarely cause extrinsic compression of the heart resulting in hemodynamically significant obstruction. We report a rare case of right ventricular outflow tract obstruction secondary to diffuse large B-cell lymphomas. Echocardiography has been found to be a useful modality in the prompt identification of mediastinal masses and their effects on the otherwise healthy heart.

Combined use of Impella left ventricular assist device and extracorporeal membrane oxygenation as a bridge to recovery in fulminant myocarditis.

Myocarditis may result in cardiogenic shock, and when medical therapy is unable to maintain adequate cardiac output, mechanical circulatory support is indicated. This is the first reported case of a percutaneous left ventricular assist device being used in combination with extracorporeal membrane oxygenation in a patient with biventricular and respiratory failure, as a bridge to recovery.