Prognostic implications of ultra-short heart rate variability indices in hospitalized patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a disease that poses a serious health risk. It is important to identify high-risk patients early in the course of their treatment. In the current study, we evaluated the prognostic value of ultra-short heart-rate variability (HRV), an index of vagal nerve activity, in IE. METHODS: Retrospective analysis was performed on adult patients admitted to a tertiary hospital due to IE. A logistic regression (LR) was used to determine whether clinical, laboratory, and HRV parameters were predictive of specific clinical features (valve type, staphylococcal infection) or severe short-term complications (cardiac, metastatic infection, and death). The accuracy of the model was evaluated through the measurement of the area under the curve (AUC) of the receiver operating characteristic curve (ROC). An analysis of survival was conducted using Cox regression. A number of HRV indices were calculated, including the standard deviation of normal heart-beat intervals (SDNN) and the root mean square of successive differences (RMSSD). RESULTS: 75 patients, aged 60.3(±18.6) years old, were examined. When compared with published age- and gender-adjusted HRV norms, SDNN and RMSSD were found to be relatively low in our cohort (75%-76% lower than the median; 33%-41% lower than the 2nd percentile). 26(34.6%) patients developed a metastatic infection, with RMSSD<7.03ms (adjusted odds ratio (aOR) 9.340, p = 0.002), incorporated in a multivariate LR model (AUC 0.833). Furthermore, 27(36.0%) patients were diagnosed with Staphylococcus IE, with SDNN<4.92ms (aOR 5.235, p = 0.004), a major component of the multivariate LR model (AUC 0.741). Multivariate Cox regression survival model, included RMSSD (HR 1.008, p = 0.012). CONCLUSION: SDNN, and particularly RMSSD, derived from ultra-short ECG recordings, may provide prognostic information about patients presenting with IE.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.

BACKGROUND: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. OBJECTIVES: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. METHODS: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. RESULTS: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. CONCLUSIONS: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.

Ultrashort Heart Rate Variability for Early Risk Stratification in Pneumonia Patients: Preliminary Analysis.

BACKGROUND: Pneumonia patients are susceptible to autonomic nervous system changes. Ultrashort HRV (usHRV) is the measurement of cyclic changes in heart rate over a period < 5 minutes. OBJECTIVES: To describe usHRV in patients with pneumonia and assess the correlation with mortality. METHODS: We conducted a retrospective analysis, which included patients diagnosed with pneumonia in the emergency department (ED). UsHRV indices were calculated from a 10-second ED electrocardiogram and correlated with mortality utilizing logistic and Cox regressions. RESULTS: The study comprised 240 patients. Mortality rates over 30, 90, and 365 days were 13%, 18%, and 30%, respectively. usHRV frequency-domain parameters had significant univariate correlations with mortality. Normalized low frequency (LF) and high frequency (HF) were correlated with 30-, 90-, and 365-day mortality in an opposite direction (odds ratio [OR] 0.094, P = 0.028 vs. OR 4.589, P =0.064; OR 0.052, P = 0.002 vs. OR 6.975, P =0.008; OR 0.055, P < 0.001 vs. OR 7.931, P < 0.001; respectively). Survival analysis was conducted for a follow-up median period of 5.86 years (interquartile range 0.65-9.77 years). Univariate Cox proportional hazard regression revealed time-domain indices with significant correlation with survival (SDNN and RMSSD; hazard ratio [HR] 1.005, 1.005; P = 0.032, P = 0.005; respectively) as well as frequency-domain parameters (normalized LF, HF, LF/HF ratio, and total power; HR 0.102, 5.002, 0.683, 0.997, respectively; P < 0.001). CONCLUSIONS: usHRV may predict mortality in pneumonia patients and serve as a novel risk stratification tool.

A prediction model for central venous catheter-related thrombosis in patients with newly-diagnosed acute myeloid leukemia: A derivation cohort analysis.

BACKGROUND: Catheter-related thrombosis (CRT) is a common complication in cancer patients, that may lead to chemotherapy deferral, elevated risk for systemic infections and pulmonary embolism. This study aimed to assess CRT incidence and risk factors in newly-diagnosed acute myeloid leukemia (AML) patients and create predictive models potentially allowing to decrease CRT occurrence in this population. METHODS: This retrospective single-center analysis included all AML patients treated at the Rambam Health Care Campus between 2006 and 2019. Patient clinical and laboratory data were collected to evaluate thrombosis occurrence and time from AML diagnosis to CRT development. Multivariate classification models were created using logistic regression (LR) and competing risk analyzes. RESULTS: The final analysis included 632 newly-diagnosed AML patients (mean age 54 ± 15 years). CRT incidence was 10.1% [confidence interval (CI) 7.7-12.9%], median time from AML diagnosis to CRT was 12.5 days [interquartile range 6-30]. In an LR multivariate model, prior history of venous thromboembolism [adjusted odds ratio (AOR) 12.046, p < 0.0001], acute promyelocytic leukemia (APL) (AOR 2.824, p = 0.015), a high body mass index and initial platelet counts <100 × 10E9/L (AOR 1.059 and 0.546; p = 0.011 and 0.040, respectively) were significantly associated with high CRT risk. Analysis of 587 non-APL patients demonstrated comparable results, with CRT incidence of 9.3% (CI 7.0%-12.1%) and emergence of chronic obstructive pulmonary disease (COPD) as a novel significant co-factor (AOR 34.491, p = 0.004). In both models, the area under curve (AUC) was ≥70%. CONCLUSIONS: Significant CRT risk factors defined using the created model could be used for identification of high-risk newly-diagnosed AML patients requiring CRT prophylaxis.

Ultra Short Heart Rate Variability Predicts Clinical Outcomes in Patients with a Clinical Presentation Consistent with Myocarditis: A Derivation Cohort Analysis.

Myocarditis prognosis varies substantially, hence identification of novel prognostic factors is crucial. The prognostic role of ultra-short heart-rate variability (HRV) in myocarditis remains unknown. In a retrospective study, adult patients admitted to a tertiary hospital due to clinically suspected myocarditis were included. Clinical, laboratory and HRV parameters were assessed as predictors of severe short term complications (heart failure (HF), dilated cardiomyopathy­DCM, ventricular arrhythmia­VA and death), utilizing logistic regression (LR). Accuracy was evaluated with receiver operating characteristic (ROC) curve area under the curve (AUC). HRV indices included standard deviation of normal beat intervals (SDNN) and root mean square of successive differences (RMSSD). 115 patients, aged 34 (±13) years old, were examined. Six patients (5%) developed severe HFrEF. RMSSD was included in a multivariate LR model (RMSSD < 10.72 ms adjusted odds ratio (AOR) 14.056, p-value 0.024). Model classification accuracy was very good, with an AUC of 86%. Eight patients (7%) developed DCM. RMSSD < 10.72 ms was included in a multivariate classification model (AOR 8.826, p-value 0.013); model classification AUC of 82%. HRV did not predict development of VA or death. SDNN and especially RMSSD may be prognostic indicators in myocarditis.

Implantable cardioverter defibrillator related Actinomyces Odontolyticus endocarditis and bacteremia-First reported case.

Actinomyces Odontolyticus is a gram-positive bacillus, usually found in the oropharynx, gastrointestinal and urogenital tracts, as commensal flora. Infections caused by this organism are rare but may occur, more commonly in immunocompromised patients. We report a case of a 54-year-old man, who presented to the emergency department (ED), with fever and chills. The patient had undergone an implantable cardioverter defibrillator (ICD) insertion, 5 months prior to his arrival, and was diagnosed with Actinomyces Odontolyticus bacteremia, during the hospitalization. Transesophageal echocardiogram (TEE) revealed vegetations on the tricuspid valve and the ICD electrode. This is the first reported case of ICD related Actinomyces endocarditis and bacteremia based on our literature review. This case emphasizes the importance of probing for the source of actinomyces infection, while considering the indolent properties of the disease.

[HEART RATE VARIABILITY: THE AGE-OLD TOOL STILL REMAINS CURRENT].

INTRODUCTION: Heart rate variability (HRV), the fluctuation in the time intervals between adjacent heartbeats, is generated by heart-brain interactions and dynamic autonomic nervous system processes. The study of HRV originated in the 18th century and served Einthoven in the development of the electrocardiogram (ECG), the basis for modern ECG technology. HRV reflects the regulation of autonomic balance, blood pressure, gas exchange, heart, and vascular tone. While 24-hour recording remains the gold standard for HRV assessment, short (5 minutes) and ultra-short (less than 5 minutes) HRV documentation is accurate and considered a more practical means of HRV measurement. HRV metrics include: time-domain indices (e.g. Standard Deviation of NN intervals (SDNN) - correlates with morbidity and mortality of patients after an acute coronary event); frequency-domain measurements (e.g. High Frequency - influenced by breathing and reflects parasympathetic activity); and non-linear analysis, which enables quantification of the unpredictability of a time series. While ECG is the cornerstone of chest pain triage, HRV may assist in the diagnosis of future cardiac disease, including heart failure and atrial fibrillation. In addition, HRV has been extensively studied as a means for risk stratification. Reduced SDNN following an acute coronary event, has been correlated with mortality. Lower SDNN levels were also associated with ventricular arrhythmia in pediatrics patients with acute myocarditis. Higher non-linear indices after an acute coronary event have been related to all-cause mortality.

Massive Gastrointestinal Bleeding from a Jejunal Dieulafoy Lesion: An Extraordinary Presentation.

We present an atypical and rare case of a previously healthy 27-year-old male who presented with acute onset of abdominal pain, bloody diarrhea, and syncope. At the Emergency Department, vital signs were stable with no signs of shock. Physical examination revealed diffuse tenderness of the abdomen and cherry red blood was noted upon rectal examination. Blood tests showed marked leukocytosis without anemia. Sigmoidoscopy was performed which revealed hematochezia with no obvious site of bleeding. The patient was admitted to the hospital with a working diagnosis of dysentery and received supportive care. During the following days, blood tests revealed an ongoing decline of hemoglobin levels which necessitated a new workup of gastrointestinal bleeding. Investigation modalities including upper and lower endoscopies as well as angiography failed to demonstrate a bleeding site. Scintigraphy, which was performed next, demonstrated an increased radiotracer activity in the right abdomen consistent with small bowel bleeding. Following these results, the patient underwent urgent laparotomy and surgical resection was performed. The histopathological findings were consistent with a Dieulafoy lesion. This case illustrates the importance of the complementary role of various modalities in locating the bleeding site along the gastrointestinal tract.