Applying natural language processing to identify emergency department and observation encounters for worsening heart failure.

AIMS: Worsening heart failure (WHF) events occurring in non-inpatient settings are becoming increasingly recognized, with implications for prognostication. We evaluate the performance of a natural language processing (NLP)-based approach compared with traditional diagnostic coding for non-inpatient clinical encounters and left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We compared characteristics for encounters that did vs. did not meet WHF criteria, stratified by care setting [i.e. emergency department (ED) and observation stay]. Overall, 8407 (22%) encounters met NLP-based criteria for WHF (3909 ED visits and 4498 observation stays). The use of an NLP-derived definition adjudicated 3983 (12%) of non-primary HF diagnoses as meeting consensus definitions for WHF. The most common diagnosis indicated in these encounters was dyspnoea. Results were primarily driven by observation stays, in which 2205 (23%) encounters with a secondary HF diagnosis met the WHF definition by NLP. CONCLUSIONS: The use of standard claims-based adjudication for primary diagnosis in the non-inpatient setting may lead to misclassification of WHF events in the ED and overestimate observation stays. Primary diagnoses alone may underestimate the burden of WHF in non-hospitalized settings.

Medical Decision-Making and Revascularization in Ischemic Cardiomyopathy.

Ischemic cardiomyopathy (ICM) is the most common underlying etiology of heart failure in the United States and is a significant contributor to deaths due to cardiovascular disease worldwide. The diagnosis and management of ICM has advanced significantly over the past few decades, and the evidence for medical therapy in ICM is both compelling and robust. This contrasts with evidence for coronary revascularization, which is more controversial and favors surgical approaches. This review will examine landmark clinical trial results in detail as well as provide a comprehensive overview of the current epidemiology, diagnostic approaches, and management strategies of ICM.

Developing Clinical Risk Prediction Models for Worsening Heart Failure Events and Death by Left Ventricular Ejection Fraction.

Background There is a need to develop electronic health record-based predictive models for worsening heart failure (WHF) events across clinical settings and across the spectrum of left ventricular ejection fraction (LVEF). Methods and Results We studied adults with heart failure (HF) from 2011 to 2019 within an integrated health care delivery system. WHF encounters were ascertained using natural language processing and structured data. We conducted boosted decision tree ensemble models to predict 1-year hospitalizations, emergency department visits/observation stays, and outpatient encounters for WHF and all-cause death within each LVEF category: HF with reduced ejection fraction (EF) (LVEF <40%), HF with mildly reduced EF (LVEF 40%-49%), and HF with preserved EF (LVEF ≥50%). Model discrimination was evaluated using area under the curve and calibration using mean squared error. We identified 338 426 adults with HF: 61 045 (18.0%) had HF with reduced EF, 49 618 (14.7%) had HF with mildly reduced EF, and 227 763 (67.3%) had HF with preserved EF. The 1-year risks of any WHF event and death were, respectively, 22.3% and 13.0% for HF with reduced EF, 17.0% and 10.1% for HF with mildly reduced EF, and 16.3% and 10.3% for HF with preserved EF. The WHF model displayed an area under the curve of 0.76 and mean squared error of 0.13, whereas the model for death displayed an area under the curve of 0.83 and mean squared error of 0.076. Performance and predictors were similar across WHF encounter types and LVEF categories. Conclusions We developed risk prediction models for 1-year WHF events and death across the LVEF spectrum using structured and unstructured electronic health record data and observed no substantial differences in model performance or predictors except for death, despite differences in underlying HF cause.

Genetic structure of major depression symptoms across clinical and community cohorts.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and aetiological subtypes. There are several challenges to integrating symptom data from genetically-informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data. We conducted genome-wide association studies of major depressive symptoms in three clinical cohorts that were enriched for affected participants (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors. The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for missing data patterns in the community cohorts (use of Depression and Anhedonia as gating symptoms). The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analysing genetic association data.

Pediatric cholesteatoma associated with congenital aural atresia and stenosis.

OBJECTIVE: Investigate presenting features, associated surgical treatment, and outcomes in patients with cholesteatoma associated with congenital aural atresia (CAA) or stenosis (CAS). METHODS: Colorado Multiple Institution Review Board approval was obtained. A retrospective chart review was performed at a single tertiary care children's hospital of all pediatric patients with congenital aural atresia or stenosis with associated cholesteatoma from January 1, 2003, to October 15, 2018. RESULTS: Of the 278 patients identified with CAA or CAS, twelve (4.3 %) were found to have a canal cholesteatoma. There was a male predominance (8:4). Nine patients (75 %) had conductive loss and three (25 %) had mixed loss. Four patients (33.3 %) exhibited canal cholesteatomas extending into the middle ear or mastoid cavity. All patients underwent surgery, and 25 % of patients required revision canalplasty while 58 % of patients required revision surgery for cholesteatoma recidivism. The average age at the time of surgery was 11.3 ± 3.7 years. CONCLUSION: Fewer than 5 % of pediatric patients with congenital aural atresia or stenosis were diagnosed with an acquired canal cholesteatoma. The need for revision surgery was common, occurring in >50 % of cases. Screening patients with CAA/CAS for cholesteatoma with imaging is recommended to avoid the morbidity of delayed identification.

Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis.

Cryptogenic stroke (CS) accounts for approximately 25% of ischemic stroke cases, with atrial fibrillation (AF) accounting for 30% of CS cases. We investigated the utility of left atrial (LA) speckle-tracking echocardiography in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long-term rhythm monitoring devices. Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF vs no AF.  We used the inverse variance method with the DerSimonian-Laird estimator for tau2 and Hartung-Knapp adjustment for random effect analysis. I2 was used to assess heterogeneity. Thirteen observational studies met our criteria and included 3031 patients with new CS. Of those, 420 patients developed AF on follow-up, and 2611 patients did not develop AF. The AF group vs. no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.61; 95% CI: -10.76, -6.47, I2 = 85%, p < 0.01] at presentation. LARS is significantly lower in patients who developed AF after CS. More studies are needed to validate this data.

The association between changes in echocardiography and risk of heart failure hospitalizations and death in adults with chronic kidney disease.

Adults with chronic kidney disease (CKD) are at increased risk for developing heart failure (HF). However, longitudinal cardiac remodeling in CKD has not been well-characterized and its association with HF outcomes remains unknown. We evaluated the association between change in echocardiographic parameters between baseline and year 4 with the subsequent risk of HF hospitalization and death using Cox proportional hazard models in a landmark analysis of a prospective multicenter CKD cohort. Among 2673 participants, mean ± SD age was 61 ± 11 years, with 45% women, and 56% non-white. A total of 472 hospitalizations for HF and 776 deaths occurred during a median (interquartile range) follow-up duration of 8.0 (6.3-9.1) years. Patients hospitalized for HF experienced larger preceding absolute increases in left ventricular (LV) volumes and decreases in LV ejection fraction. Adverse changes in LV ejection fraction, LV cavity volume, LV mass index, and LV geometry were independently associated with an increased risk of HF hospitalization and death. Among adults with CKD, deleterious cardiac remodeling occurs over a relatively short timeframe and adverse remodeling is associated with increased risk of HF-related morbidity and mortality.

Successful Management of Hemodynamically Unstable Takotsubo Cardiomyopathy With Milrinone.

Takotsubo cardiomyopathy (TTC) was initially reported in the 1990s as a reversible cause of cardiomyopathy induced by acute emotional stress. It is characterized by regional systolic dysfunction in the absence of coronary artery disease. We report a case of a 79-year-old woman who was admitted with acute respiratory failure due to pneumonia and was found to have a troponin elevation. Upon further evaluation, the patient was taken to the cardiac catheterization lab and underwent catheterization which showed apical ballooning concerning Takotsubo cardiomyopathy. She was placed on a norepinephrine drip but remained unstable. Milrinone-facilitated diuresis was then initiated with improvement and stabilization in hemodynamics. Takotsubo cardiomyopathy presenting with cardiogenic shock without left ventricular outflow tract obstruction requires treatment with inotropes. Although there is limited data to support the use of milrinone in cardiogenic shock due to TTC, its use in our case facilitated diuresis and improved the patient's outcome after norepinephrine failed to stabilize our patient's hemodynamics. Milrinone inhibits phosphodiesterase type 3 which increases the calcium influx thereby improving the myocardial contraction without any beta agonist action. Therefore, the use of milrinone which is a non-catecholamine inotrope could be considered a better alternative as compared to dobutamine given the underlying pathophysiology of TTC.

Remdesivir-Induced Extreme Sinus Bradycardia in COVID-19.

During the COVID-19 pandemic, there was an urgent need for any medication to help reduce the high death rate experienced during this deadly surge. Remdesivir is an FDA-approved drug for COVID-19 treatment, given its anti-inflammatory properties. Upon extensive literature search, we found two studies and four cases of COVID-19-induced pneumonia treated with remdesivir who were developing bradycardia. In most of these cases, the bradycardia resolved within one-to-two days of holding remdesivir, which correlated with the half-life of remdesivir. Remdesivir was shown to have benefits in COVID-19-induced pneumonia during the COVID-19 surge; however, its use has been controversial. According to the studies, the sinus bradycardia following remdesivir administration does not impact patients' prognosis in terms of ICU admission and in-hospital mortality. There are multiple case reports noted to report several remdesivir-induced cardiac side effects. In our case, prolonged use and high dosages may induce cardiotoxicity, manifesting as severe bradycardia. Several possible mechanisms for cardiac adverse effects with remdesivir need further investigation and research as COVID-19 remains an active global issue. We present a 53-year-old man hospitalized with COVID-19-induced pneumonia who experienced extreme sinus bradycardia that is likely attributable to remdesivir.

Early Manifestation of Clozapine-Induced Cardiotoxicity: Detection, Pathophysiology, and Management.

Schizoaffective disorder, bipolar type is a chronic mental health disorder that may manifest as mania. Clozapine is effective in treating acute mania and in achieving mood stabilization. However, on rare occasions, the use of clozapine has been associated with cardiotoxicity. Here, we present a case of a 31-year-old man who at baseline is known to have schizoaffective disorder, bipolar type, and cannabis dependence and was admitted to our hospital with a psychotic relapse. He was treated with clozapine, uptitrated to a maximum daily dose of 200mg twice daily by day 10. Thereafter he became febrile and experienced malaise, myalgias, and chest pain. He was noted on electrocardiogram to have sinus tachycardia without ischemic changes. In this context, he had a troponin leak, increased white blood cell count, serologies and cultures were negative and chest x-ray revealed no acute disease of the chest. Due to the suspicion of clozapine-induced cardiotoxicity, a transthoracic echocardiogram was done, which revealed mildly depressed left ventricular (LV) systolic function without pericardial effusion. Thereafter, clozapine was withdrawn and switched to lithium. Additionally, the cardioselective, metoprolol tartrate was initiated. Within 36-48 hours, he had resolution of symptoms and remained cardiovascularly stable. Clozapine uncommonly causes cardiotoxicity and early features may be non-specific. Awareness of this and recognizing early features aids in reducing the associated cardiovascular morbidity and mortality.

Inappropriate Subcutaneous Implantable Cardioverter Defibrillator Shocks Secondary to Cardiac Remodeling: A Unique Case of T Wave Oversensing.

Implantable cardioverter defibrillators (ICD) are used for the primary and secondary prevention of sudden cardiac death (SCD). Currently, two different modalities of ICDs are in use: transvenous (TV) and subcutaneous (S-ICD). The use of S-ICDs has been driven by several potential benefits of this technology: preservation of central venous vasculature, no risk of vascular or myocardial injury during implant, easier explanation, and lower risk of systemic infections. Inappropriate shocks are defined as shocks delivered for non-life-threatening arrhythmias or because of oversensing. Here, we present a case of a 58-year-old man who began experiencing inappropriate shocks three years after S-ICD placement. Careful analysis of the ICD showed T wave oversensing with no malfunction of the device. The shocks persisted even after reprogramming, leading to subsequent ICD removal and loop recorder implantation. The onset of shock episodes coincided with the improvement of left ventricular ejection fraction (LVEF). To the best of our knowledge, this is the first published report of cardiac remodeling leading to uncorrectable T wave oversensing that subsequently required S-ICD explant. This represents a potentially important limitation of S-ICD technology, especially as S-ICD use rises and medical therapy for cardiomyopathy continues to improve.

Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk.

Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression.

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

A Diagnostically Challenging Parotid Gland Tumor With Hybrid Features.

Salivary gland tumors are relatively uncommon with most being benign. When diagnosed the most common benign and malignant tumors are pleomorphic adenoma and mucoepidermoid carcinoma (MEC), respectively. However, not uncommonly, it is difficult to differentiate between the histopathological entities, leading to a diagnostic dilemma that can impact a patient's treatment and prognosis. A 24-year-old woman presented with a three-year history of asymptomatic left-sided facial swelling. She denied any prior history of head and neck radiation. There was no history of alcohol consumption or smoking exposure and there was no personal or family history of head and neck cancers. Additionally, she did not have any known occupational or environmental exposures. Due to the chronicity and painless nature of this facial mass, our patient did not pursue evaluation initially. Subsequently, she experienced an increase in size and pain for a few months exacerbated by swallowing. She had no other symptoms. On physical examination, a 3 x 3 cm left parotid gland mass was noted. There was no associated head or neck lymphadenopathy and compression of the left facial mass did not elicit secretions from the opening of Stensen's duct. Due to the rapid increase in size, she was sent for CT neck/soft tissue with contrast which confirmed a 3.56 x 2.67 cm solid nodule within the superficial portion of the left parotid gland. This was followed by an MRI orbit/face/neck with and without contrast, for further delineation, which demonstrated a 4 x 3.7 x 3 cm complex heterogeneous mass within the superficial left parotid gland. Thereafter the patient underwent an uncomplicated ultrasound-guided biopsy of the parotid mass. The histopathological appraisal concluded that this was a cellular pleomorphic adenoma, with mucinous and squamous metaplasia with reactive lymph nodes. Due to the new rapid increase in size and intense painful nature of this tumor, nerve-sparing left parotidectomy, fat grafting and reconstruction were completed. Cellular pleomorphic adenomas are benign low-grade neoplasms, typified as biphasic with both epithelial and myoepithelial components. However, they have increased cellularity and focally increased mitotic activity, not advanced enough to qualify as malignant. The presence of mucinous and squamous metaplasia is of diagnostic interest as it makes diagnosis on fine-needle aspiration (FNA) morphologically challenging. These findings are typical of MEC and on FNA can be misleading in the setting of a pleomorphic adenoma. However, on histopathological evaluation of the gross specimen along with immunohistochemical staining the diagnosis is made much easier. A diagnosis of MEC would have potentially required neck dissection and adjuvant therapy with a potential increased risk of morbidity and mortality. This case emphasises the importance of an adequate tissue biopsy in regards to parotid gland tumors to optimise a patient's care plan.

Transient Cardiac Dysfunction Following a Cerebrovascular Accident.

Acute cerebral injuries are often accompanied by sudden electrocardiogram (ECG) changes such as cardiac arrhythmias, QT prolongation, and abnormal T-wave morphology. One rare phenomenon is "cerebral T-waves", which are T-waves observed in the context of stroke and described as transient, symmetric, and deeply inverted. The classic cerebral T wave is defined as a T-wave inversion of ≥5 mm depth in at least four contiguous precordial leads, and it is more commonly observed in the setting of acute ischemic stroke rather than hemorrhagic stroke. We describe the case of a patient who initially presented with acute pulmonary edema, T-wave inversions in the precordial leads, and left ventricular dysfunction on echocardiogram raising suspicion of an ischemic cardiac event. However, a brain CT scan performed on the third day of admission proved us wrong.

Left Ventricular Non-compaction Cardiomyopathy: Delayed Diagnosis and Deleterious Outcomes.

Cardiomyopathy and associated heart failure have uncommon etiologies, which when diagnosed reduce patients' morbidity and mortality. One such entity is left ventricular non-compaction cardiomyopathy (LVNC). Still, a relatively uncommon entity, the manifestation of LVNC may range from asymptomatic to left ventricular dysfunction, congestive heart failure, ventricular tachycardia, sudden cardiac death, and thromboembolic complications. If not pursued as a possible etiology of non-ischemic cardiomyopathy, patients may have significantly increased morbidity prior to eventual diagnosis. Patients are often predisposed to ventricular arrhythmias requiring implantable cardiac defibrillator placement. Additionally, due to the depth of trabeculations, there is an associated thromboembolic risk requiring therapeutic anticoagulation. We present the case of a 41-year-old man with progressively worsening heart failure due to undiagnosed LVNC and the associated deleterious manifestations and outcomes.

The association between genetically determined ABO blood types and major depressive disorder.

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.

Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19: A Meta-Analysis and Systematic Review.

Introduction Increased virulence, the severity of illness, and mortality have all been hypothesized with respect to angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) use in coronavirus disease 2019 (COVID-19) infection. Our study aims to assess whether ACEi/ARB use in patients with COVID-19 conferred worsened severity of illness or increased mortality. Additionally, we explore the possibility of an unearthed protective benefit due to their interruption of the RAS signaling pathway as observed in cardiovascular diseases. Methods The Cochrane Library, MEDLINE, and EMBASE were searched for studies relevant to COVID-19 severity, mortality, and inflammation in the context of ACEi/ARB use. Eight studies were included with a total of 17,943 patients, 4,292 (23.9%) of which were taking an ACEi or an ARB. The study population was 47.9% female and the average age across all studies was 65. The studies chosen had a sample size of at least 100 patients. Results Mortality outcomes were assessed in six studies and showed no significant difference in mortality among the ACEi/ARB and control groups (odds ratio [OR]: 0.99, 95%CI: 0.48-2.04). Seven studies assessed the severity of COVID-19 and showed no statistically significant difference in disease severity when comparing the ACEi/ARB group to the control group (odds ratio [OR]: 1.30, 95% CI 0.87-1.94). Four studies reported the length of stay with no significant difference between the ACEi/ARB groups as compared to non-users. Four studies included inflammatory markers C-reactive protein (CRP) and D-Dimer, which were noted to be consistently lower in the ACEi/ARB groups when compared to control groups, however, this was not statistically significant. Conclusion Our study found no significant difference in mortality, severity of illness, or length of stay between ACEi/ARB users and non-users with COVID-19 infection. These results support the continuation of ACEi and ARBs in the setting of COVID-19 as advised by the American College of Cardiology (ACC)/American Heart Association (AHA). The decrease in CRP and D-dimer suggests a possible protective effect related to ACEi/ARB use in COVID-19, however, more studies with larger sample sizes are needed to establish this effect.

Retraction: Transient Cardiac Dysfunction in Cerebrovascular Accidents.

[This retracts the article DOI: 10.7759/cureus.10185.].