Flecainide overdose-induced wide-complex tachyarrhythmia treated with sodium bicarbonate infusion.

Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval.

Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition.

The objective was to correlate CD47 gene expression with resistance to immune checkpoint inhibitors (ICI) in tumor tissue of gynecological cancer (GC). Further, we sought to assess the efficacy of targeting CD47 pathway alone and in combination in pre-clinical ovarian cancer (OC) models. We performed transcriptomic analyses in GC treated with ICI. Signaling pathway enrichment analysis was performed using Ingenuity Pathway Analysis. Immune cell abundance was estimated. CD47 expression was correlated with other pathways, objective response, and progression-free survival (PFS). Anti-tumor efficacy of anti-CD47 therapy alone and in combination was investigated both in-vitro and in-vivo using cell-line derived xenograft (CDX) and patient-derived xenograft (PDX) models. High CD47 expression associated with lower response to ICI and trended toward lower PFS in GC patients. Higher CD47 associated negatively with PDL1 and CTLA4 expression, as well as cytotoxic T-cells and dendritic cells but positively with TGF-ß, BRD4 and CXCR4/CXCL12 expression. Anti-CD47 significantly enhanced macrophage-mediated phagocytosis of OC cells in-vitro and exhibited potent anti-tumor activity in-vivo in OC CDX and PDX models. In-vitro treatment with PARPi increased CD47 expression. Anti-CD47 led to significantly enhanced in-vitro phagocytosis, enhanced STING pathway and synergized in-vivo when combined with PARP inhibitors in BRCA-deficient OC models. This study provides insight on the potential role of CD47 in mediating immunotherapy resistance and its association with higher TGF-ß, BRD4 and CXCR4/CXCL12 expression. Anti-CD47 showed potent anti-tumor activity and synergized with PARPi in OC models. These data support clinical development of anti-CD47 therapy with PARPi in OC.

Cardiac Sarcoidosis With Elevated Cardiac Troponin Mimicking Acute Myocardial Ischemia: A Case Report.

Cardiac sarcoidosis (CS) is a disease entity with variable presentation causing significant morbidity and mortality. Concurrent signs of myocardial injury as evidenced by troponin elevation add to the complexity of an already challenging diagnosis. We present an unusual case of CS with elevated troponin I mimicking an acute ischemic cardiac event. A 48-year-old female presented with a two-month history of presyncope.  Electrocardiogram showed a bifascicular block with concomitant significant troponin I elevation. Two-dimensional echocardiography showed new-onset left ventricular systolic dysfunction with an ejection fraction of 40-45%. A heparin drip was initiated for possible non-ST-elevation myocardial infarction. Coronary angiography showed no evidence of epicardial coronary artery disease but did show an anomalous right coronary artery; however, CT angiography did not reveal any significant stenosis. Further, the telemetry monitor captured intermittent complete atrioventricular blocks. Due to concerns for an infiltrative cardiac disease, a cardiac magnetic resonance was done showing findings consistent with possible CS.  CT scan of the chest showed no radiographic evidence of pulmonary sarcoidosis. Fluorodeoxyglucose-positron emission tomography scan showed findings of active inflammation in the myocardium consistent with possible CS. The patient was treated for clinical CS with systemic corticosteroids and methotrexate. Follow-up six weeks later showed clinical improvement of symptoms. Our clinical case encompasses the unique variable presentation of CS including cardiac conduction abnormalities and left ventricular systolic dysfunction. Concomitant troponin I elevation can mimic myocardial ischemia, making the diagnosis more challenging. Treatment strategies aim to mitigate the long-term effects of CS on the heart; however, there is a paucity of data for appropriate pharmacological regimens.

Retrospective analyses of the outcomes among hospitalized liver cirrhosis patients with heart failure and COVID-19 infection: Insight from the National Inpatient Sample.

Background: There is paucity of data regarding the impact of Coronavirus Disease 2019 (COVID-19) infection on the outcomes of hospitalized liver cirrhosis (LC) patients with heart failure (HF). Methods: Utilizing the 2020 National Inpatient Sample (NIS) Database, we conducted a retrospective cohort study to investigate the outcomes of hospitalized LC patients with HF and COVID-19 infection, looking at its impact on in-hospital mortality, risk for acute kidney injury (AKI) and length of stay (LOS). Results: We identified a total of 10,810 hospitalized LC patients with HF, of which 1.39 % (n = 150/10,810) had COVID-19 infection. Using a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, COVID-19 infection among hospitalized LC patients with HF was found to be an independent predictor of overall in-hospital mortality (aOR 3.73; 95 % CI, 1.58-8.79; p = 0.00) and risk for AKI (aOR 3.06; 95 % CI, 1.27-7.37; p = 0.01) compared to those without COVID-19 infection. However, there were comparable rates of LOS among LC patients with HF regardless of COVID-19 infection status. Moreover, AKI was found to be an independent predictor of longer LOS (coefficient 4.40, 95 % CI 3.26-5.38; p = 0.00). On subgroup analysis, diastolic HF was found to be associated with increased risk for in-hospital mortality (aOR 6.54; 95 % CI, 2.02-21.20; p = 0.00), development of AKI (aOR 3.33; 95 % CI, 1.12-9.91; p = 0.03) and longer LOS (coefficient 4.30, 95 % CI 0.79-9.45; p = 0.03). Conclusion: Concomitant COVID-19 infection among hospitalized LC patients with HF was associated with higher risk for in-hospital mortality and AKI but did not significantly affect hospital LOS.

Systolic Anterior Motion of the Mitral Valve in the Presence of Annular Calcification.

BACKGROUND: Mitral annular calcification (MAC) has been reported as a possible cause of systolic anterior motion (SAM) of the mitral valve and dynamic left ventricular outflow tract (LVOT) obstruction. While morphologic features predisposing to SAM in other clinical settings have been described, patients with MAC+SAM have not been systematically investigated. We hypothesized that bulky calcium deposits in the mitral annulus could displace the valve toward the septum, thus promoting development of SAM. METHODS: We studied 30 patients with severe MAC who had SAM with septal contact. Three comparator groups (matched for age and sex) were developed: 30 controls without MAC or SAM, 30 with severe MAC but no SAM, and 30 with SAM but no MAC. RESULTS: Significant differences were found across groups for mitral valve coaptation point-septal distance (CSD), anterior mitral leaflet (AML) length, left ventricular diastolic dimension, and ejection fraction. Comparing all MAC subjects (n = 60) with controls, CSD was less (20.5 ± 4.1 vs 23.2 ± 3.7 mm, P = .003) and ejection fraction was higher (67.7% ± 7.8% vs 60.9% ± 6.4%, P < .0001) in MAC patients. Within MAC subjects AML was longer (21.9 ± 3.0 vs 17.4 ± 2.2 mm, P < .0001) and CSD was smaller (18.0 ± 2.7 vs 23.1 ± 3.6 mm, P < .0001) when SAM was present despite similar height of the calcium bar in the 2 MAC groups (12.4 ± 2.9 vs 11.1 ± 3.1 mm, P = .11). Regression analysis confirmed AML length and CSD as independent predictors of SAM. MAC+SAM patients also had more echocardiographic risk factors for SAM (acute aortomitral angle, small LVOT, long AML, small CSD, and presence of a septal bump) than MAC/no-SAM patients (3.4 ± 0.9 vs 1.8 ± 1.0, P < .0001). CONCLUSIONS: Bulky MAC appears to contribute to dynamic LVOT obstruction when it accumulates in such a way that the mitral valve is displaced anteriorly toward the septum. However, other features are also associated with SAM in these patients, particularly a long AML. A combination of morphologic features and favorable hemodynamics may be needed for SAM to develop in patients with severe MAC.

Subaortic Membrane Co-existing With Hypertrophic Cardiomyopathy: A Clinically Challenging Diagnosis.

Subaortic Membrane is the most common type of subaortic stenosis. That, coexisting with hypertrophic obstructive cardiomyopathy (HOCM) is an extremely rare combination and clinically underappreciated. In this report, we will discuss an 18-year-old male patient who presented with chest pain and dyspnea due to fixed (sub-aortic membrane), as well as dynamic (HOCM), left ventricular outflow tract obstruction (LVOT) obstruction.

Reverse Takotsubo Cardiomyopathy After Casirivimab-Imdevimab Therapy in a Patient with COVID-19: A Case Report.

BACKGROUND Takotsubo cardiomyopathy, also referred to as apical ballooning syndrome (ABS), stress cardiomyopathy, or broken heart syndrome, initially described in Japan, is characterized by transient wall motion abnormalities involving the apical segment. Several variants have been described, including reverse type, mid-ventricular type, and the focal type. In the reverse type, there is basal hypokinesis and apical hyperkinesis. Stress cardiomyopathy is most likely to occur in middle-aged women and the underlying etiology is believed to be related to catecholamine release due to intense stress. CASE REPORT We report an extremely rare case of reverse takotsubo cardiomyopathy (rTTC) in a young woman with COVID-19 who was treated with Casirivimab-Imdevimab therapy. Our report is the second to reveal rTTC in a patient with COVID-19 in which obstructive coronary artery disease was definitively ruled out by coronary CT angiography. CONCLUSIONS Cardiovascular involvement in COVID-19 has been linked to increased morbidity and mortality rates. Recent reports have suggested the occasional occurrence of TTC and the rare occurrence of reverse takotsubo cardiomyopathy (rTTC) in patients with COVID-19. In fact, to the best of our knowledge, this is only the fifth reported case of rTTC in a patient with COVID-19; importantly, 3 out of the 4 of the previous reported cases lacked definitive ischemic work-up to rule out obstructive coronary artery disease due to the critical condition of the patients.

Malaria Falciparum: Relapse After a Decade.

Malaria is an infection caused by the Plasmodium malaria (PM) parasite. There are still cases of malaria that are reported in the United States on an annual basis. All these cases were a result of travelers who did not receive or follow their prescribed chemoprophylaxis, recommendations for avoiding mosquito bites while traveling, or relapsed dormant plasmodium. The malaria parasite can be transmitted by the bite of an infected female mosquito, through contact with infected blood products, or from mother to child during pregnancy through the placenta. It can take anywhere from 12 to 20 days for symptoms to appear, but there are cases of delayed development and/or relapse that can occur up to 13 years after the infection. We report a 31-year-old female with a history of malarial infection in Liberia, which had been treated ten years prior to her arrival in the United States. She presented to the hospital with abdominal pain, fever, and headache. She was eventually diagnosed with plasmodium malaria infection relapse and treated with a 14-day course of primaquine 300 mg daily, with the symptoms resolving a few days after. We believe her malarial infection was caused by a dormant malarial parasite that evaded the immune system and relapsed without having a risk factor for relapse or re-infection 10 years after her original infection.

Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.

The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's ß-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.

Atypical Presentation of Babesiosis With Neurological Manifestations as Well as Hematological Manifestations.

Babesiosis is an infectious disease that is typically known to present with fevers, chills, and myalgias; and less commonly with anorexia, headache, nausea, and vomiting. The least common are shortness of breath, sore throat, neck stiffness, emotional lability, photophobia, and dark urine. Even more unusual are severe neurologic manifestations like altered mental status, motor deficits, and ataxia. We present two cases of patients, both in their seventies, with multiple comorbidities, who were admitted with similar symptoms of confusion/cognitive impairment, slurred speech, ataxia, fever, myalgias and chills, urinary frequency, and urgency, with no previous history of travel outside the country or tick bites. Both patients had extensive workup, which raised suspicion of hemolytic infections, especially babesiosis and malaria. Considering our patients had not traveled out of the country, we leaned more toward babesiosis. The patients were treated appropriately for babesiosis and were also empirically treated for Lyme's, anaplasmosis, along with Mycoplasma in the second patient. Following two days of treatment, cognition, as well as speech, improved dramatically. On outpatient follow-up, both patients had entirely resolved hemolysis, parasitic load, and neurological manifestations. During the literature review, neurologic manifestations, being associated with babesiosis, were found to be exceedingly rare but could be fatal if left undiagnosed. It is an infection that is associated with complete recovery on prompt diagnosis and treatment. It is pertinent to have a high suspicion of this disease, especially in endemic areas, such as the Northeast United States, even more so when seen with hematologic and neurologic manifestations.

Differences in ejection fraction as inclusion criterion in randomized controlled trials among patients with heart failure with reduced ejection fraction: a systematic review.

INTRODUCTION: Heart failure (HF) with reduced ejection fraction (HFrEF) has been defined by varying ejection fraction (EF) criteria in clinical trials, leading to differences in quantifying treatment effects. AREAS COVERED: The definitions of HFrEF in randomized controlled trials from 2010 until 2020 were collected. The EF ranges were clustered into very low (<30%), low (30-39%) and mildly reduced (40-49%) stratified by intervention. A time series regression analysis was performed. A total of 3052 articles were screened and 706 were included. Interventions included were pharmacologic (37%), device therapy (10%), and a combination of programs, procedural, and laboratory testing (53%). Regarding EF cutoffs, 41% of the studies utilized <40% while 26% used <35%. About 31% did not have a clearly defined EF. Between 2010 and 2020, studies with HFrEF ranges 30-39% have significantly decreased (p value < 0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40-49%) have remained the same. EXPERT OPINION: EF definitions across clinical trials in HFrEF varied widely. Defining the specific target HF population phenotype when designing trials or in patient treatment is important as various beneficial effects of different heart failure treatment modalities can be modified or even attenuated across the spectrum of EF.

Osteonecrosis of Bilateral Distal Femurs in a Pregnant Patient Following Antenatal Betamethasone.

Corticosteroid therapy is a known risk factor for osteonecrosis, more commonly with chronic use and high cumulative dose. Osteonecrosis (avascular necrosis) has been described in pregnancy involving primarily the femoral head. To our knowledge, only rare cases of femoral meta diaphysis or knee osteonecrosis in pregnancy have been documented in the literature. We report a 28-year-old woman with sickle cell trait and beta-thalassemia trait who developed severe bilateral knee pain shortly after corticosteroid therapy. She was 34-weeks pregnant when she presented with the signs of preterm labor and was found to have oligohydramnios and preeclampsia. She was given two intramuscular injections of betamethasone 12 mg one day apart to enhance the fetal lung maturity. Within hours of the second injection, she developed acute and severe bilateral knee pain affecting her mobility and ambulation. Bilateral knee x-rays were unremarkable. Given the severity and persistence of her pain, magnetic resonance imaging (MRI) of bilateral lower extremities was done few days later and showed signs of early osteonecrosis involving bilateral distal femoral meta diaphysis and right lateral femoral condyle. Other than the steroid therapy she had received, no additional extrinsic risk factors for osteonecrosis were identified. Potential intrinsic risk factors were thought to include her combined sickle-beta-thalassemia traits and pregnancy. She was diagnosed with steroid-induced osteonecrosis, given the temporal relationship. Her presentation was unique, because osteonecrosis affected unreported sites during pregnancy, and it started shortly after a brief course of antenatal steroid. She was treated conservatively with analgesics, and outpatient orthopedic follow-up was recommended. She was advised to avoid prolonged weight-bearing and strenuous activities. On a follow-up appointment two months later, she was still complaining of bilateral knee pain with ambulation though it was less severe. She did not return for follow-up thereafter. We suggest the possibility of osteonecrosis in pregnancy involving uncommon sites, such as distal femur and femoral condyle in this case, following one or two doses of systemic steroid. Obstetricians need to consider osteonecrosis when evaluating an unexplained musculoskeletal pain after betamethasone that is used for preterm labors. More studies, including reporting more cases with unusual presentation and prospective studies following pregnant patients receiving steroid therapy, are needed to better understand the causes, associations, management, and clinical course of osteonecrosis in pregnancy.