AI-Enhanced Reconstruction of the 12-Lead Electrocardiogram via 3-Leads with Accurate Clinical Assessment.

The 12-lead electrocardiogram (ECG) is an integral component to the diagnosis of a multitude of cardiovascular conditions. It is performed using a complex set of skin surface electrodes, limiting its use outside traditional clinical settings. We developed an artificial intelligence algorithm, trained over 600,000 clinically acquired ECGs, to explore whether fewer leads as input are sufficient to reconstruct a full 12-lead ECG. Two limb leads (I and II) and one precordial lead (V3) were required to generate a reconstructed synthetic 12-lead ECG highly correlated with the original ECG. An automatic algorithm for detection of acute myocardial infarction (MI) performed similarly for original and reconstructed ECGs (AUC=0.94). When interpreted by cardiologists, reconstructed ECGs achieved an accuracy of 81.4±5.0% in identifying ST elevation MI, comparable with the original 12-lead ECGs (accuracy 84.6±4.6%). These results will impact development efforts to innovate ECG acquisition methods with simplified tools in non-specialized settings.

Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

Baseline natriuretic peptides as a predictor of atrial fibrillation recurrence after radiofrequency-based pulmonary vein isolation in a non-heart failure population: A subanalysis from DECAAF II.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of myocardial stretch and may have prognostic significance in patients with atrial fibrillation (AF) without heart failure (HF). We investigated the association between baseline BNP levels and arrhythmia recurrence following pulmonary vein isolation (PVI) among patients with persistent AF without HF. METHODS: We analyzed 125 patients with persistent AF without HF who had baseline BNP measured from the DECAAF II trial. The primary outcome was arrhythmia recurrence following ablation. The baseline characteristics across the two groups were compared using Chi-square test and Wilcoxon rank test accordingly. Cox regression analysis was used to analyze the association between baseline BNP levels and the primary outcome. RESULTS: Across the entire cohort, 64 (51%) patients experienced arrhythmia recurrence. When comparing patients who experienced arrythmia recurrence to patients who did not, patients with recurrent arrhythmia had higher levels of pre-ablation BNP, as evidenced by differences in means (330.05 pg/mL) compared to patients without recurrent arrhythmia (182.39 pg/mL) (p < .05). A cut-off BNP value of 300 pg/mL provided the largest area under curve (AUC) of receiver-operating characteristic (ROC) curve on univariate logistic regression. On unadjusted Cox analysis, for every 100 unit increase in BNP, the hazard ratio for the primary outcome increased 1.09 (1.026-1.158) times (p = .004). After adjusting for sex, hypertension, and stroke, the results remained significant (HR = 1.8516, CI 95% [1.0139 - 3.381], p = .045). CONCLUSION: In the non-heart failure population, BNP levels predict AF recurrence following PVI in persistent AF patients.

Nutrient optimization for indigenous microbial consortia of a Bhagyam oil field: MEOR studies.

The microbial enhanced oil recovery (MEOR) method is an eco-friendly and economical alternative technology. The technology involves a variety of uncertainties, and its success depends on controlling microbial growth and metabolism. This study is one of a kind that showed successful tertiary recovery of crude oil through indigenous microbial consortia. In this study, a medium was optimized to allow ideal microbial growth under reservoir conditions through RSM. Once the nutrient recipe was optimized, the microbial metabolites were estimated through gas chromatography. The maximum amount of methane gas (0.468 mM) was produced in the TERIW174 sample. The sequencing data set showed the presence of Methanothermobacter sp. and Petrotoga sp. In addition, these established consortia were analyzed for their toxicity, and they appeared to be safe for the environment. Furthermore, a core flood study showed efficient recovery that was ~25 and 34% in TERIW70 and TERIW174 samples, respectively. Thus, both the isolated consortia appeared to be suitable for the field trials.

Wild type cardiac amyloidosis: is it time to order a nuclear technetium pyrophosphate SPECT imaging study?

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.

6 month serologic response to the Pfizer-BioNTech COVID-19 vaccine among healthcare workers.

AIM: Healthcare workers (HCWs) were among the first group of people vaccinated with the Pfizer-BioNTech Covid-19 vaccine (BNT162b2). Characterization of the kinetics of antibody response to vaccination is important to devise future vaccination strategies. To better characterize the antibody response to BNT162b2, we analyzed the kinetics of IgG and IgM antibody response to 5 different SARS-CoV-2 epitopes over a period of 6 months. METHODS AND RESULTS: An observational single-centered study was conducted to evaluate the temporal dynamics of anti-SARS-CoV-2 antibodies following immunization with two doses of BNT162b2. Anti-SARS-CoV-2 antibodies were assessed using the Maverick SARS-CoV-2 multi-antigen panel (Genalyte Inc.). Healthcare workers aged ≥18 receiving BNT162b2 vaccination who self-reported no prior symptoms of COVID-19 nor prior COVID-19 PCR test positivity, were included in this study. HCWs developed an IgG antibody response to SARS-CoV-2 Spike S1, Spike S1 receptor binding domain (RBD), Spike S1S2 and Spike S2 after vaccination. IgG response was observed at two weeks following immunization in most participant samples and continued to increase at week 4, but subsequently decreased significantly starting at 3 months and up to 6 months. In contrast, IgM response to respective epitopes was minimal. CONCLUSION: Multiplex results demonstrate that, contrary to natural infection, immunization with BNT162b2 produces minimal anti-Spike IgM response. Polyclonal IgG response to Spike declined at 3 months and continued to do so up to 6 months.

Hospitalization requiring intensive care unit due to SARS-CoV-2 infection correlated with IgM depression and IgG elevation.

AIM: This study investigated the humoral response against SARS-CoV-2 in patients needing intensive care unit (ICU) care compared with those on general medicine wards. MATERIALS & METHODS: The authors retrospectively reviewed 113 hospitalized patients with COVID-19. They assessed antibody response against five SARS-CoV-2 epitopes at 6-14 days post symptom onset in these patients. RESULTS: Patients with ICU admissions had decreased anti-nucleocapsid immunoglobulin (Ig)M and increased anti-spike IgG compared with patients not requiring the ICU. IgG levels were positively correlated with length of stay. CONCLUSION: Higher levels of IgG against the spike protein correlate with COVID-19 disease severity and length of stay in hospitalized patients. This adds to the knowledge of biochemical response to clinical disease and may help predict ICU needs.

A Comprehensive Explanation Framework for Biomedical Time Series Classification.

In this study, we propose a post-hoc explainability framework for deep learning models applied to quasi-periodic biomedical time-series classification. As a case study, we focus on the problem of atrial fibrillation (AF) detection from electrocardiography signals, which has strong clinical relevance. Starting from a state-of-the-art pretrained model, we tackle the problem from two different perspectives: global and local explanation. With global explanation, we analyze the model behavior by looking at entire classes of data, showing which regions of the input repetitive patterns have the most influence for a specific outcome of the model. Our explanation results align with the expectations of clinical experts, showing that features crucial for AF detection contribute heavily to the final decision. These features include R-R interval regularity, absence of the P-wave or presence of electrical activity in the isoelectric period. On the other hand, with local explanation, we analyze specific input signals and model outcomes. We present a comprehensive analysis of the network facing different conditions, whether the model has correctly classified the input signal or not. This enables a deeper understanding of the network's behavior, showing the most informative regions that trigger the classification decision and highlighting possible causes of misbehavior.

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels.

BACKGROUND: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose. HYPOTHESIS: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine. METHODS: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V. RESULTS: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine. CONCLUSIONS: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch in Rats With Heart Failure.

BACKGROUND: To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. METHODS: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n = 12) or left coronary artery ligation (n = 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. RESULTS: Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), ß-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. CONCLUSIONS: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.

Right atrial myxoma presenting as a pulmonary embolism in a 32-year-old female.

Primary cardiac tumors are typically benign, with myxomas being most common. We present a 32-year-old female with a chief complaint of dyspnea and a constant non-radiating chest pressure along the left sternal border. She was found to have a pulmonary embolism that was ultimately caused by embolization of a right atrial myxoma with remnants of a large, highly mobile mass attached to the right inter-atrial septum prolapsing through the tricuspid valve. The patient underwent a median sternotomy, right atrial mass resection, pulmonary embolectomy, and inter-atrial septum reconstruction using the patient's pericardium. The importance of finding the etiology of initial diagnoses is stressed with long-term outcomes for patients.

Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells.

Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.