Acute or chronic? Failing left ventricle in a 34 year old

Submission content Introduction: An unusual case of a very young patient without previously known cardiac disease presenting with severe left ventricular failure, detected by a point of care echocardiogram. Main Body: A 34 year old previously well man was brought to hospital after seeing his general practitioner with one month of progressive shortness of breath on exertion. This began around the time the patient received his second covid-19 vaccination. He was sleeping in a chair as he was unable to lie flat. Abnormal observations led the GP to call an ambulance. In the emergency department, the patient required oxygen 5L/min to maintain SpO2 >94%, but he was not in respiratory distress at rest. Blood pressure was 92/53mmHg, mean 67mmHg. Point of care testing for COVID-19 was negative. He was alert, with warm peripheries. Lactate was 1.0mmol/L and he was producing more than 0.5ml/kg/hr of urine. There was no ankle swelling. ECG showed sinus tachycardia. He underwent CT pulmonary angiography which demonstrated no pulmonary embolus, but there was bilateral pulmonary edema. Troponin was 17ng/l, BNP was 2700pg/ml. Furosemide 40mg was given intravenously by the general medical team. Critical care outreach asked for an urgent intensivist review given the highly unusual diagnosis of pulmonary edema in a man of this age. An immediate FUSIC Heart scan identified a dilated left ventricle with end diastolic diameter 7cm and severe global systolic impairment. The right ventricle was not severely impaired, with TAPSE 18mm. There was no significant pericardial effusion. Multiple B lines and trace pulmonary effusions were identified at the lung bases. The patient was urgently discussed with the regional cardiac unit in case of further deterioration, basic images were shared via a cloud system. A potential diagnosis of vaccination-associated myocarditis was considered,1 but in view of the low troponin, the presentation was felt most likely to represent decompensated chronic dilated cardiomyopathy. The patient disclosed a family history of early cardiac death in males. Aggressive diuresis was commenced. The patient was admitted to a monitored bed given the potential risk of arrhythmia or further haemodynamic deterioration. Advice was given that in the event of worsening hypotension, fluids should not be administered but the cardiac centre should be contacted immediately. Formal echocardiography confirmed the POCUS findings, with ejection fraction <35%. He was initiated on ACE inhibitors and beta adrenergic blockade. His symptoms improved and he was able to return home and to work, and is currently undergoing further investigations to establish the etiology of his condition. Conclusion(s): Early echocardiography provided early evidence of a cardiac cause for the patient's presentation and highlighted the severity of the underlying pathology. This directed early aggressive diuresis and safety-netting by virtue of discussion with a tertiary cardiac centre whilst it was established whether this was an acute or decompensated chronic pathology. Ultrasound findings: PLAX, PSAX and A4Ch views demonstrating a severely dilated (7cm end diastolic diameter) left ventricle with global severe systolic impairment.

Use of metolazone as an adjunct therapy to loop diuretics in diuretic resistant acute decompensation of heart failure: A systematic review and meta-analysis: Metolazone in diuretic resistant AHF: A Meta-Analysis

Introduction: Loop diuretics are the first-line treatment for volume overload in acute decompensation of congestive heart failure (AHF). Loop diuretic resistance is common due to pharmacologic tachyphylaxis. Therefore, thiazide and thiazide-like diuretics are often used as add-on therapy to combine two different pharmacologic mechanisms. This systemic review and meta-analysis aimed to synthesize the current evidence on the efficacy and safety of metolazone and other thiazide-like diuretics in AHF. Method(s): PRISMA guidelines were followed in conducting this systematic review. PubMed, Scopus, PubMed Central, and Embase databases were searched using relevant keywords for studies published before 5 Jan 2022. and title screening was performed, followed by full-text screening using the Covidence software. Data were extracted, and analysis was done using Cochrane Review Manager (RevMan v5.1). The results were reported in odds ratio and mean difference with 95% confidence intervals. Result(s): Out of 2999 studies identified by database search, eight studies met the inclusion criteria (2 RCTs and 6 cohort studies). Pooled analysis using a random-effects model showed no difference in mean difference among the metolazone group and control group for 24 hours total urine output (MD 69.32, 95% CI -638.29 to 776.94;n = 551;I2 = 84%), change in urine output in 24 hours (MD -284.09, 95% CI -583.99 to 15.81;n = 345;I2 = 0%), 48 hours total urine output (MD -465.62, 95% CI -1302.22 to 370.99;n = 242;I2 = 0%) and urine output at 72 hours (MD -13.24, 95% CI -90.88 to 64.40;n = 205;I2 = 0%). However, studies with furosemide only in the comparator arm, 24 hours of total urine outcome favored metolazone (MD 692.70, 95% CI 386.59 to 998.82;n = 334;I2 = 0%). There was no difference between the two groups in the rate of adverse events, loss of weight, mortality, or readmission rates. Conclusion(s): Metolazone therapy in diuretic resistant AHF may improves urine output and facilitates achieving a net negative balance. Thus, metolazone and thiazide-like diuretics can be used as add-on therapy in acute decompensation of heart failure, especially in diuretic resistance.Copyright © 2023 The Author(s)

PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

Seasonal and Covid Pandemic-Related Variations in Patients0 Self-Reported Adherence to Nutrition Recommendations for Stone Prevention Suggest Temporal Increases in Stone Recurrence Risk

INTRODUCTION AND OBJECTIVE: Nutrition therapy for stone prevention is indicated if risks are diet-related. Dietary recommendations (DRs) include higher fluid intake, lower salt intake, lower dietary acid load, and normal calcium (neither excessive nor insufficient). Adherence is challenging to assess and optimally includes multiple measures including patient-reported outcomes. We assessed adherence to individualized targeted DRs issued in our multidisciplinary stone prevention clinic. METHOD(S): From 1/2020-1/2021 we invited patients to complete a questionnaire 1 month after their appointment. They were to estimate the number of days within the last week they followed specific DRs prescribed them and number of days they followed all DRs. Questionnaires were sent by mail with postage-paid return envelopes. This was a quality improvement project;patients were offered to respond anonymously. RESULT(S): Respondents (n=132) represented 29% of patients who were sent questionnaires and were 50% female (61+/-13 y). Of those providing clinical details, 77% were recurrent stone formers;46% were on stone medication(s). There were no adherence differences for men vs. women, recurrent vs. one-time stone formers, nor for those on stone-related medications vs. not. Overall, adherence to eating more F/ V was lower (4.7 vs. 5.5 d/week for all other DRs, p<0.004). We separated responses by receipt: summer/fall (April to mid-November) and winter/spring (mid-November to April), and by pre- vs. post- COVID (before/after March 2020). F/V intake was significantly lower during winter/spring than summer/fall (4.4 vs. 5.5 d/week, p=0.009). Related to the COVID pandemic, patients reported lower adherence to all DRs after the pandemic start (5.0 vs. 5.9 d/week, P=0.009 for difference from before). CONCLUSION(S): Overall, adherence to eating more F/V was significantly lower than for other DRs and was lower yet during winter/ spring. The COVID pandemic did not affect F/V intake specifically but did reduce adherence to all DRs. F/V are important in stone prevention because they provide HCO3 precursors that increase urine citrate and pH. F/V also provide other stone inhibitors, including phytate (which in urine inhibits calcium stone formation) and prebiotics, some of which enhance oxalate-degrading gut bacteria. Moreover, F/V intake can account for up to 30% of urine output and thus may help meet fluid recommendations. Barriers to F/V intake, which may include seasonal variations in cost and availability, should be addressed .

Impact of Crystalloid Administration on Patients Receiving Haploidentical Allogeneic Stem Cell Transplant (Haplo SCT) with Post Transplant Cytoxan Prophylaxis (PtCy): a Quality Improvement Initiative

Background: Crystalloid fluid administration has traditionally played an important role in prevention of hemorrhagic cystitis with high dose cyclophosphamide. Cryopreservation of stem cells in the era of the COVID pandemic has further led to an increase in crystalloid use. Excess fluid administration over a short duration could lead to volume overload, respiratory failure and impact overall survival. Method(s): A retrospective chart review was conducted on patients receiving PtCy following Haplo SCT at UVA Medical Center from September 2016 through August 2022. Internal BMT quality audit in June 2021 identified increased rate of ICU transfers and respiratory failure amongst patient receiving PtCy due to fluid overload. Hence our PtCy hydration was reduced, with IV fluid administration decreasing from 200 mL/ hr over 62 hours to 100 mL/hr over 12 hours. Urine output parameters placed to administer Cytoxan were also removed. We present our quality improvement project demonstrating outcomes pre and post intervention. Result(s): All demographic patient and transplant-related data was collected during the period of hospitalization for Haplo SCT [Table 1]. Pre-intervention spanned 9/2016-8/2021. Our analysis identified higher than expected rates of respiratory (Table Presented) failure prompting intervention on 8/2021. Post-intervention spanned 8/2021-8/2022. Pre-intervention, 45% of patients receiving Haplo SCT developed respiratory failure (defined as a new hypoxia) in the 30 day post-transplant period. Of these, 93% had volume overload. Mechanical ventilation was required in 21%. Complication rates included ICU transfer - 30%, AKI - 39%, and renal replacement therapy - 18%. Three percent (1 pt) developed hemorrhagic cystitis requiring bladder irrigation. Median LOS was 31.0 days. Post-intervention, average IV crystalloid received was reduced by about 15L. Median diuretic use reduced by 40%. No instances of respiratory failure, mechanical ventilation, ICU transfer, AKI or renal replacement therapy occurred in this group. Median LOS was 26.5 days. There were no cases of hemorrhagic cystitis. Please refer Figure 1. (Figure Presented) (Figure Presented) Conclusion(s): This single center quality improvement initiative shows that reducing IV crystalloid administration with PtCy is associated with a reduction in respiratory failure and other adverse clinical outcomes, without observed increase in hemorrhagic cystitis. Larger multi-center studies are needed to validate this finding.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Renal safety of liposomal amphotericin B in critically ill mechanically ventilated patients with SARS-CoV-2 pneumonia

Introduction: Liposomal amphotericin B (L-AmB) represent a good treatment strategy for critically ill patients according to its unique pharmacological characteristics and a relatively broad spectrum of action. The aim of the present study is to asses the impact on renal function of L-AmB during the first days of ICU admission in critically ill patients. Method(s): Retrospective, single-center case series of patients with SARS-CoV-2 pneumonia admitted in ICU. Setting(s): 19-bed medical-surgical ICU of a community hospital. Time of study: 2 years. Study variables: APACHE II and SOFA at admission, clinical characteristics, oliguria and creatinine level at admission and 72 h after L-AmB treatment were recorded. Oliguria was defined as urinary output less than 400 ml per day or less than 20 ml per hour. Two groups of patients were selected according to whether or not they received anticipated antifungal treatment pending microbiologic confirmation or discarding of aspergillosis;dosage of L-AmB was 3 mg/kg/d. Statistical analysis: Data were analyzed by SPSS 18 and quantitative variables were expressed as a mean +/- standard deviation. Result(s): 160 patients were included, 102 who received 3 days of anticipated treatment with L-AmB at ICU admission or at the beginning of mechanical ventilation were compared with patients without this treatment. There were not differences in age, median 65 [57-71] years, gender with 28% female and BMI (kg/m2), 30,4 [26,6-33,2]. APACHE II at admission was higher in the treated group of patients 17 [12-23] vs 12 [9-14]. SOFA was 7 [4-8] in the treated group of patients vs 6 [3-8]. There were not differences in urinary output between groups during the three first days of ICU stay. Table 1 shows creatinine levels. Conclusion(s): According to our retrospective analysis, L-AmB is safe in the first days of treatment in critically ill patients admitted in ICU requiring mechanical ventilation.

Massive polyuria associated with severe COVID-19-related pneumonia complicated by pulmonary embolism

Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.

The Significance of Epidermal Growth Factor and Other Urinary Cytokines since Subclinical Aki in Patients with Covid-19

Introduction: In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with the kidney stress biomarkers neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein (IGFBP7) in COVID-19 patients without AKI at study entry. Method(s): Prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at the time they were enrolled to the study. Urine samples were collected on admission to critical care areas for determination of NGAL, [TIMP-2]*[IGFBP7] and cytokines concentrations with a second sample 5 days after the first urine sample. Demographic information, clinical and laboratory data were collected. Diagnosis and staging of AKI were based on KDIGO criteria using serum creatinine (sCr) levels and urine output. The urinary concentrations of TIMP-2 and IGFBP7 were determined ELISA in the same way NGAL. The concentrations of cytokines and chemokines in urine were measured with a Luminex 200 instrument. We performed descriptive statistics including means and standard deviations for normally distributed continuous variables;medians and interquartile ranges (IQR) for non-parametric distributions;and proportions for categorical variables. Logistic regression analysis was used to identify the association between relevant covariates with AKI. Principal component analysis (PCA) was performed to compress and simplify the size of the data set by keeping the most important information and analyzing the structure of the observations and the variables. Correlation of identified cytokines with kidney stress biomarkers was explored using the Spearman test. All statistical tests were two-sided, p values <0.05 were considered statistically significant. The analysis was conducted using R Studio 1.4.1717. Result(s): Of included 51 patients. Of those, 30 were males (58.8%);the median age was 53 years (IQR: 40-61);14 had systemic arterial hypertension (27.5%);16 had diabetes (31.4%);and 21 were obese (41.2%). 54.9% developed AKI. After adjusting for possible confounding variables, only EGF >4600 pg/ml remained associated with lower risk of AKI (OR=0.095, 95% CI: 0.01-0.81, p=0.031.In the PCA of day 1, Epidermal Growth Factor (EGF) and interferon (IFN)-alpha were associated with a lower risk of AKI (OR=0.24, 95% CI: 0.07-0.78, p=0.017), while Interleukin (IL)-12 and macrophage inflammatory protein (MIP)-1b were associated with a higher risk of AKI (OR=51.09, 95% CI: 2.12-1233, p=0.015). In the PCA of day 5, EGF and IFN-alpha remained associated with a lower risk of AKI (OR=0.09, 95% CI: 0.01-0.74;p=0.024), while IL-1 Receptor, granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI (OR=7.7, 95% CI: 1.06-55.74, p=0.043). EGF had an inverse correlation with [TIMP2] x IGFBP7] (R-0.73, p=<0.001) and with NGAL (R= -0.63, p=0.002). Conclusion(s): Subclinical AKI was characterized by a significant up-regulation of NGAL, TIMP-2, IGFBP7 and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-alpha antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm. No conflict of interestCopyright © 2023

Effect of Hemoperfusion on the Clinical Outcome of Severe and Critical Covid-19 Patients Admitted at the University of Santo Tomas Hospital: An Analytical Cohort Study

Introduction: Severe sepsis is a life-threatening end organ dysfunction resulting from dysregulated host response to infection and poses a significant burden to healthcare systems worldwide. Since the advent of CoVID-19, cytokine release syndrome has also been attributed to clinical deterioration presenting as acute respiratory distress syndrome and acute kidney injury of infected individuals. Objective(s): To determine the clinical outcome of Severe and Critical COVID-19 patients who underwent hemoperfusion compared with patients who did not undergo hemoperfusion. Method(s): This study entailed a retrospective cohort analysis of patients aged >= 18 and < 90 years old admitted at University of Santo Tomas Hospital who were diagnosed with Severe or Critical COVID-19. Subjects were grouped between those who underwent hemoperfusion (HP group) using HA 330 cartridge and those who did not undergo the procedure (non-HP). Demographic and clinical data collected for both groups included age, sex, comorbidities present, time to initiation of hemoperfusion, total hemoperfusion time, use of other medications specifically: immunomodulator and anti-viral drugs, antibiotics and steroid, length of hospital stay and in-hospital mortality. Mean arterial pressure, cardiac rate, oxygen saturation, arterial blood gas, complete blood count, oxygen requirement, inotropic score, serum creatinine, urine output, lactate dehydrogenase (LDH), ferritin, high sensitivity C-reactive protein (HsCRP), Interleukin-6 values and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared from baseline and after 4 sessions of hemoperfusion for the HP group. The clinical outcomes: length of hospital stay, in-hospital mortality and time to off high flow nasal cannula (HFNC) between two groups were also compared. Result(s): A total of 98 cases were included, 49 subjects underwent hemoperfusion using HA 330 and 49 patients did not undergo hemoperfusion. Demographic data is similar between both groups. Baseline clinical data between Hemoperfusion and non-Hemoperfusion group did not show statistical difference. However, Baseline LDH, HsCRP, Ferritin, IL-6, PF ratio and APACHE II score were statistically different between two groups. Effect on Disease Severity Length of hospital stay and time to off HFNC was shorter in the non-HP group vs the HP group, median of 13 days vs 18 days (p-value 0.003) and 107 hours vs 222 hours (p- value <0.001), respectively. There is also no significant difference in in-hospital mortality between two groups. [Formula presented] [Formula presented] [Formula presented] Conclusion(s): This retrospective study did not show survival benefit with the use of hemoperfusion. Undergoing hemoperfusion did not show a significant effect on changes in disease severity as represented by no significant difference seen in APACHE II score, PF ratio, acute kidney injury, length of hospital stay and in-hospital mortality. Hemoperfusion also has no significant effect in terms of decreasing the values of inflammatory markers LDH, ferritin, and IL-6. A large, multi-center, randomized clinical trial is warranted to truly determine the clinical benefit of hemoperfusion not only in severe to critical COVID-19 but also in severe sepsis and conditions that trigger systemic inflammatory response and cytokine storm. *This abstract was also submitted for the ISN Frontiers:Infections and the Kidneys congress. No conflict of interestCopyright © 2023

Acute Transcatheter Aortic Valve Replacement Failure Secondary to Covid-19 Infection

Background Valve thrombosis is a documented cause of prosthetic valve failure. Common features include increased cusp thickness, reduced cusp mobility, and increased transvalvular gradient. Case reports have been published of prosthetic valve thrombosis secondary to COVID-19 infection, but this may represent the first documented case of bioprosthetic transcatheter aortic valve replacement (TAVR) thrombosis in the setting of COVID-19. Case A 90 year-old female with atrial fibrillation on apixaban and severe aortic stenosis status-post TAVR with normal valve function on recent echocardiogram presented in clinic with acute chest pain. She was found to have COVID-19 infection and severe bioprosthetic valvular regurgitation with leaflet thickening, abnormal cusp mobility, and elevated transvalvular gradient. [Formula presented] Decision-making Given the time course of valve failure, COVID-19 infection, and echocardiographic features, the patient was diagnosed with bioprosthetic valve thrombosis secondary to COVID-19. She was optimized with diuresis and continued on apixaban before undergoing valve-in-valve TAVR with resolution of valvular dysfunction. Conclusion This case contributes to a body of literature describing thrombotic complications in patients with valve replacement and COVID-19 infection despite concurrent anticoagulation. Increased vigilance and investigations are warranted to better characterize thrombotic risk and optimal antithrombotic strategies in this patient populace.Copyright © 2023 American College of Cardiology Foundation

A Rare Case of Heart Failure in Third Trimester Pregnancy - Diagnostic and Therapeutic Dilemma

Background Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an extremely rare disorder. Case A 20-year-old, 36-week pregnant female (G1P0) presented with acute shortness of breath, sharp chest pain and fever. She was COVID-19 positive and required BiPAP. Echocardiogram showed 40% EF, dilated LV with global hypokinesis and moderate mitral regurgitation (MR). She was hypotensive and on oxygen despite diuresis, emergent cesarean and COVID-19 treatment. Left heart catheterization showed anomalous takeoff of the left main coronary artery (LCA) from the dilated pulmonary artery (PA) with coronary steal (Figure 1). She had ALCAPA repair with LIMA to LAD bypass grafting. Decision-making Differential diagnoses included peripartum cardiomyopathy, Covid-myocarditis, pulmonary embolism, and spontaneous coronary artery dissection. LHC was performed only when symptoms failed to improve and troponin kept rising. ALCAPA has two major clinical subtypes - Infantile type and adult type. Adult type presents as dyspnea, chest pain, reduced exercise ability, and sudden cardiac death. Despite having good RCA to LCA collaterals, adult patients can still have ongoing ischemia of the LV myocardium, causing ischemic MR, malignant ventricular dysrhythmias. Diagnosis was delayed due to pregnancy and COVID-19 infection. Conclusion ALCAPA is a lethal coronary disorder. Elevated troponin and dilated cardiomyopathy with acute MR should raise suspicion of ALCAPA in young adults. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Acute Myocarditis: Secondary to Viral Infection or Pheochromocytoma?

Background In a young healthy patient, acute cardiogenic shock with a dilated, thickened left ventricle is strongly suggestive of acute myocarditis. Case SM is a 33 year-old healthy man who presented with decompensated heart failure with severe hypervolemia. Notably, he was exposed to Hand-Foot-Mouth disease (HFMD) two weeks prior. B-type natriuretic peptide was elevated at 3,417 pg/mL (normal range < 50 pg/mL), and troponin was elevated. Echocardiogram revealed dilated, severe systolic dysfunction with thickened left ventricular walls. He progressed to cardiogenic shock and multi-organ failure. Right heart catheterization revealed significantly reduced cardiac output and index of 2.36 and 1.2, respectively. His course was complicated by left ventricular thrombus and subacute embolic stroke, acute renal failure and liver failure. He was treated with afterload reduction, inotropes, and diuresis. His shock resolved, and he improved with medical therapy for cardiomyopathy. Decision-making The clinical course is consistent with acute myocarditis leading to cardiogenic shock with multi-organ failure. A broad differential was considered, including viral etiologies, autoimmune diseases, vasculitis, and toxin-mediated myocarditis. Viral labs including COVID-19 and influenza, as well as HIV, and hepatitis B and C viruses were negative. Coxsackie B2 antibody was positive at 1:80, which is consistent with past or current infection. Rheumatology evaluation was unrevealing, and vasculitis was deemed unlikely given normal inflammatory markers. Urine drug screen was unrevealing. However, adrenergic myocarditis remained on the differential given an adrenal nodule noted on imaging. Plasma free metanephrines were significantly elevated, consistent with pheochromocytoma. Conclusion This is a case of acute myocarditis with two likely etiologies. The patient's presentation correlates temporally with exposure to HFMD, suggesting viral myocarditis. However, he had gross hypervolemia and diuresed 50 pounds, which suggests a more indolent course. We propose that he had adrenergic myocarditis and undetected cardiomyopathy which was exacerbated by a second insult, the Coxsackie virus.Copyright © 2023 American College of Cardiology Foundation

The headache of diagnosing cerebellitis

Case Report:We describe a case of a non-verbal 5-yearold patient with autism and global developmental delay who presented with headache, nausea, vomiting, and decreased oral intake and found to have acute cerebellar syndrome/cerebellitis secondary to COVID-19 infection. Method(s): Chart Review. Summary of Results: A 5-year-old male with autism spectrum disorder and global developmental delay presented with one week history of headache, nausea, and non-bilious, non-bloody emesis. Despite intravenous fluid resuscitation and anti-emetic treatment, the patient continued to have persistent emesis with decreased oral intake and urine output. Physical exam findings were notable for aniscoria with right pupil larger than left, fixed upward gaze deviation, horizontal nystagmus, and nuchal rigidity. Patient was able to move all extremities spontaneously with normal tone and without rigidity or hyperreflexia. A complete blood cell count was consistent with the following: WBC 17.29 K/uL, hemoglobin level 12.8 g/dL, hematocrit 38.9%, and platelet count 482 K/ uL. C-reactive protein <4.0 mg/L and procalcitonin 0.12 ng/mL. CT Head on hospital day one showed no acute intracranial abnormality. Due to the patient's acute neurological changes, MRI brain was obtained and revealed patchy areas of hyperintensity in both the cerebellar hemispheres with moderate swelling of the cerebellum causing narrowing of the posterior fossa extra-axial cerebrospinal fluid (CSF) spaces. In addition, there was obstruction of the cerebral aqueduct due to extrinsic mass effect by the swollen cerebellum. CSF studies were notable for the following: 148 total nucleated cells with 75% lymphocytes and 17% monocytes and 2 red blood cells, protein was elevated at 113 mg/dL, and glucose was normal at 52 mg/dL. Meningitis and encephalitis panel was without any acute findings. Other laboratory testing was negative for tuberculosis, syphilis, chlamydia, HIV, and EBV. The patient tested positive for COVID-19 virus about one month prior to the onset of symptoms. Imaging and laboratory results in the setting of obstructive hydrocephalus with associated symptoms of nausea, emesis, headache, and upward gaze deviation are consistent with acute cerebellar syndrome, or cerebellitis. Due to obstructive hydrocephalus and inflammation of the cerebellum, patient was started on high-dose steroids, and neurosurgery placed external ventricular drain (EVD). The patient worked closely with physical medicine and rehabilitation as well as speech therapy, physical therapy, and occupational therapy to make a full recovery following this illness. Conclusion(s): Headache, nausea, and vomiting are often seen as benign findings;however, it is important to obtain specific details regarding the timing of symptoms, especially in the setting of a non-verbal patient. Because inflammation of the cerebellum can lead to hydrocephalus and potential herniation, prompt diagnosis is crucial to prevent long term effects of cerebellitis. Copyright © 2023 Southern Society for Clinical Investigation.

Protein losing enteropathy (PLE) secondary to norovirus infection in a 4 year old patient

Case Report: Protein losing enteropathy (PLE) occurs when proteins leak from the gastrointestinal (GI) system more rapidly than they are produced. Inflammation of the GI tract facilitates increased membrane permeability of gastric mucosa, leading to excess protein leakage. 1 PLE in children has been associated with CMV, rotavirus, COVID-19, HIV, C. difficile, and autoimmune diseases like Crohn's Disease. 2-6 Norovirus is a known cause of PLE in immunocompromised pediatric patients. 7-8 However, to our knowledge, there are no case reports about PLE precipitated by norovirus in immunocompetent pediatric patients. The purpose of this case report is to present a case of PLE precipitated by a norovirus infection in a 4- year-old previously healthy child. While the above gastrointestinal viruses have been proposed as precipitators for this disease, PLE precipitated by norovirus infection has not been well described. This case also highlights the importance of early diagnosis and management to avoid complications. Method(s): Our patient initially presented with two days of abdominal pain, diarrhea, emesis, reduced urine output, and swelling of the lower extremities. He was exposed to several sick family members-his sister had upper respiratory symptoms and his grandmother had gastrointestinal symptoms. Physical exam was notable for diminished breath sounds in the right lower lobe, abdominal distension with diffuse tenderness and dullness to percussion, significant scrotal and penile edema, and bilateral lower extremity pitting edema. Laboratory results revealed leukocytosis, hypoalbuminemia, hyponatremia, elevated aspartate aminotransferase (AST), and elevated serum alpha-1-antitrypsin, as well as low Immunoglobulins G and M. CD3 and CD4 levels were low reflecting cellular immune dysregulation seen in patients with PLE. IgA and Tissue Transglutaminase (TTF) were within normal limits. Ebstein Barr Virus and cytomegalovirus IgM antibodies were negative. COVID IgG was negative as well. His Polymerase chain reaction (PCR) gastrointestinal panel was positive for norovirus. A chest X-ray showed a large right pleural effusion. Abdominal CT revealed large ascites slightly more predominant in the upper abdomen, mesenteric lymphadenitis, and bilateral pleural effusions. Echocardiogram showed small anterior and apical pericardial effusions. Result(s): Based on the patient's elevated serum alpha-1 antitrypsin levels, hypoalbuminemia, low levels of immunoglobulins and lymphocytes, and clinical manifestations of ascites, bilateral pleural effusions, pericardial effusion, and dependent edema, along with a positive PCR for norovirus, the diagnosis of PLE secondary to Norovirus was made. Conclusion(s): This case demonstrates the importance of recognizing viruses like Norovirus as potential causes of PLE to avoid a delay in diagnosis and initiation of therapy, and to avoid unnecessary additional testing. Copyright © 2023 Southern Society for Clinical Investigation.

Infant with syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to infant botulism

Objectives To become familiar with the appearance of SIADH in infant botulism Methods A-43 day old male with no significant history presented to the ED with difficulty latching and decreased activity for 2 days. At the ED, he was afebrile, hypoxic to 82% with moderate respiratory distress. Non-invasive positive pressure ventilation was started and he was placed on systemic antibiotics due to concern for sepsis. Initial labs showed positive rhinovirus/enterovirus, but otherwise normal CMP (Na 140 mmol/l), CBC, CRP, VBG, UA, negative COVID-19 and blood culture after 48 hours. CXR showed right upper lobe consolidation. Patient received a bolus of NS and maintenance IVF afterwards for less than 24 hours. He was placed on continuous orogastric feeds during the second day of hospitalization with his usual home formula regimen while weaning IVF. Patient started showing periorbital edema and his neurologic status deteriorated with hypotonia, diminished reflexes and lethargy. During the 5th day of hospitalization, he had a focal seizure of the left lower extremity that lasted about 2 minutes that promptly resolved after lorazepam administration. Labs sent during that episode were significant with Na of 113 mmol/l, urine Na of 94 mmol/l, urine Osm of 383 mOs/kg, and serum Osm of 271 mOs/kg consistent with SIADH, however, he did not have increased urine output. Rest of labs and imaging of the head and spine were normal. Patient received 0.9% NS and 3% hypertonic solution and sodium started to normalize over the course of 24 hours and remained stable during the rest of the hospital course on IV fluids. Due to profound hypotonia and aforementioned progressive clinical course while ruling out other possible causes with different specialties, concern for infant botulism was discussed and infectious disease was consulted. Recommendations included sending stool sample for botulism, avoiding the use of any aminoglycoside, and starting botulism immune globulin (BabyBIG) Results Patient received BabyBIG 50mg/kg about 10 days after initial admission and started improving immediately the day after administration. Neurologic status and respiratory effort subsequently started improving significantly and patient was able to be extubated after a week. Infant was eventually confirmed for botulism toxin A via stool Conclusions SIADH is thought to be due to reduced atrial filling from venous pooling in paralysis and is known to be a common complication of infant botulism and should be considered when patient has hyponatremia.

CRRT impact on outcomes of patients treated with ECMO and fluid overload: a case report

Background: ECMO is an extracorporeal circulation used as a short-term life-saving support in patients with refractory cardiac and respiratory failure. Fluid overload (FO) in patient with this support, sometimes due to the onset of AKI, is associated with an increased morbidity and mortality rate and with prolonged duration of mechanical ventilation and ECMO. It also alters the volume of distribution of most drugs and can even mask the presence of AKI. Mantaining a negative fluid balance is an essential goal to improve gas exchanges in patients with respiratory failure who have undergone ECMO support. So, fluid overload removal has a significant prognostic value. Diuretic therapy, at the maximal dosage, can be insufficient to reach a negative water balance and it can also lead to metabolic disorders. Initiating RRT may help to obtain this goal. Method(s): A 32-years-old man, without any comorbidity, was admitted to the intensive care unite (ICU) with severe acute respiratory distress syndrome (ARDS) due to SARS Cov-2 infection and refractory hypoxemia. After intubation and mechanical ventilation, he was treated with VV-ECMO. In order to maintain a negative fluid balance, diuretic therapy at maximum dosage was started. Despite this therapy, the patient continued to show fluid overload clinical and its radiological signs, with a little improvement in gas exchanges. For that reason and in order to avoid metabolic alterations due to the diuretic therapy, it was decided to start CVVHF treatment. Thus, the patient was submitted to 3 sessions of CVVHF with a total ultrafiltration of 12 liters. He never lost spontaneous diuresis (his hourly dieresis was about of 150 ml). Diuretic therapy was restarted at the end of the CRRT sessions. Result(s): There was an improvement in patient's gas exchanges already during the first treatment which led to the stop of ECMO after 14 days. FGF (fresh gas flow) had been progressively decreased to the oxygenator. At the same time, lung ventilation has been increased to maintain an adequate CO2 clearance. The patient remained stable at a FGF of 0 L/min for a period of 24 hours;thus only mechanical ventilation was kept. A negative fluid balance has led to a significant patient's clinical conditions improvement to permit VV-ECMO weaning. Conclusion(s): Fluid overload removal is an essential goal to improve gas exchanges and, consequently, outcomes in patients treated with ECMO and its duration can both improve. This goal requires continuous renal replacement therapy (CRRT) because of patient's hemodynamic instability. However, the approach combining CRRT and ECMO is facilitated by several ways to link the different circuits without the necessity of positioning a bilumen CVC and, also, by using the same anticoagulation regimen.

A Case Series on Glomerular Disease Manifesting for the First Time after Covid 19 Vaccination

BACKGROUND: Different vaccines have been developed against SARS nCoV 19 and deployed in mass immunization campaigns across the world. In India, Covishield (ChAdOx1 nCoV-19) manufactured by Serum Institute of India) and Covaxin (BBV152) manufactured by Bharat Biotech are two such vaccines that have been made available. The former is a replication-deficient adenovirus vaccine while the latter is an inactivated whole virion vaccine. There has been many case reports of new onset or relapse of glomerular disease occurring after Covid-19 vaccination. This is attributed to heighten off target effect of immune response of the vaccine. AIM OF THE STUDY: We present a case series of four patients where glomerular disease manifested for the first time after Covid-19 vaccination in our center. METHOD(S): We have included in our case series those patients whose clinical features manifested for the first time within 1 month of Covid-19 vaccination and whose renal biopsy showed glomerular pathology. RESULT(S): Case 1: A 12-year-old male presented to us with abrupt onset of edema leading to anasarca on 30/4/2022. He had received first dose of Covid-19 vaccine (Covaxin) on 26/4/2022. His labs showed urine protein of 3+ and nil RBC, serum creatinine 0.7 mg/dl, serum albumin 1.9 mg/dl, and dyslipidemia (total cholesterol 378 mg/dl, triglycerides 191 mg/ dl). He underwent renal biopsy in view of nephrotic syndrome. It was suggestive of minimal change disease. He was started on prednisolone at 2 mg/kg/day. Case 2: A 39-year-old female presented to us with abrupt onset of maculopapular rash, fever, and bilateral lower limb swelling on 25/1/2022. She had received second dose of Covid-19 vaccine (Covishield) on the same day in the morning. She was found to have hypertension with BP of 160/100 mm Hg. Her labs showed urine protein of 2+ and 18-20 RBC/high power field, serum creatinine 1.9 mg/dl, serum albumin 3.7 mg/dl, negative ANA and ANCA, and normal complement levels. She underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of focal and segmental glomerulosclerosis (FSGS). Case 3: A 37-year-old male patient with history of hypertension (on irregular treatment) presented to us with history of gross hematuria without passage of clots in May 2022 about three days after receiving booster dose of Covishield vaccine. He did not have edema, rash, joint pain, or decreased urine output. His labs showed urine protein of 2+ and 5-6 RBC/high power field, serum creatinine 2.0 mg/dl, serum albumin 4.0 mg/dl, negative ANA and ANCA, and normal complement levels. He underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of IgA nephropathy (M1E0S1T1C0). Case 4: An 18-year-old female with family history of nail patella syndrome presented to us with history of abrupt onset of edema of both lower limbs on 21/11/2021. She also had rash at the time of presentation. She had received first dose of Covid-19 vaccine (Covaxin) on 20/11/2021. Her labs showed urine protein of 2+ and numerous RBC/high power field, serum creatinine 1.4 mg/dl, serum albumin 2.98 mg/dl, negative ANA, and dsDNA and low complement levels (C3 14.1 mg/dl, C4 10.1 mg/dl: both being low). She underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of membranoproliferative glomerulonephritis (MPGN). She was started on prednisolone at 1 mg/kg/day. CONCLUSION(S): Different vaccines have different mechanisms of action, but their target remains the spike protein of the SARS Cov2 virus. Glomerular disease has mostly been reported with mRNA-based vaccines. Here we have reported glomerular disease occurring in close temporal relation to Covishield and Covaxin which have different mechanism of action. There have been reports of IgA nephropathy, minimal change disease and FSGS which manifested soon after vaccination. MPGN after Covid-19 vaccination is rarely seen. Thus, this case series shows that post- Covid vaccination glomerular disease can have varied pathologies.

New Onset Cmv Disease in Post Renal Transplant Patients in Association with Covid19 Infection - 2 Cases and Brief Review of Literature

BACKGROUND: Several cases of CMV syndrome and invasive CMV infection have been reported following COVID19 infection worldwide during COVID19 pandemic in both immunocompetent and immunosuppressed patients. AIM OF THE STUDY: We intend to discuss more about the interrelationship of COVID19 and CMV infection in renal transplant patients. METHOD(S): We discuss two clinical cases, and we present a brief review of literature. 30-year-old man with end-stage primary lupus nephritis underwent mother-to-son kidney transplantation. Post-transplant surgery the patient was discharged with 1.8 mg/ml baseline creatinine. After 3 months, he was admitted with complaints of fever for 4 days with no derangement of renal function. He tested positive for COVID 19 infection and was managed conservatively. Subsequently within 10 days, he was readmitted with chief complaints of loose stools abdominal pain and back pain with mildly raised creatinine and leukopenia. CMV PCR detected 128500 copies per ml. This patient was treated with injection ganciclovir and GM-CSF injection. Mycophenolate mofetil was withheld in view of CMV infection. However, the patient complained of persistent back pain with gradual decline in graft and renal function. With decreasing urine output, dialysis was initiated. Subsequently, the patient developed altered sensorium and had cardiac arrest. 34-year-old male with end-stage chronic nephritis had undergone cadaveric kidney transplantation. Post-transplant the patient had delayed onset graft function with baseline creatinine of 2 mgdl on the 10th post-operative day. Subsequently, the patient suffered from active antibody-mediated rejection, and the patient was managed with six cycles of plasmapheresis. One month later, the patient was admitted with fever and cough. The patient tested positive for COVID19 infection and was managed conservatively. Simultaneously, the patient developed multiple episodes of hematochezia pain in abdomen and diarrhea. Urine output was maintained with stable creatinine. Stool routine and microscopic examination revealed multiple RBCs few pus cells - however no parasite was detected. CMV PCR was positive with 3000 copies per ml. The patient was initially treated with injection ganciclovir and was switched to oral valganciclovir. The patient remained afebrile general condition improved with no further episodes of hematochezia and gradual decline of creatinine to baseline level. RESULT(S): In both our cases, COVID19 infection were managed conservatively, and CMV infection was treated with stoppage of mycophenolate mofetil and addition of ganciclovir injection and resulted into one positive and one negative clinical outcome. CONCLUSION(S): CMV reactivation after COVID 19 infection in renal transplant patient may be a common phenomenon. Further studies are immediately needed to know whether CMV viremia should be routinely tested in all renal transplant patients in India who get COVID19 infection. Studies are also required to determine if clinical outcomes of CMV disease after COVID19 infection in renal transplant patients are different from CMV disease outcomes in other renal transplant patients who have no history of immediately preceding COVID 19 infection.

Spectrum and Outcomes of Acute Kidney Injury in a Non-Covid Intensive Care Unit during Covid Pandemic: Single Centre Study from North India

BACKGROUND: Acute kidney injury (AKI) is a major risk factor for mortality in ICU patients. The aim of this study was to evaluate the spectrum and outcomes of non-COVID related AKI admitted to non-COVID intensive care units of a tertiary care hospital during COVID pandemic. AIM OF THE STUDY: To study the Spectrum and Outcomes of Acute Kidney Injury in a Non-COVID Intensive Care Unit during COVID Pandemic METHODS: Patients were prospectively enrolled from February 2020 to June 2021 using a predesigned standardized pro forma as per the inclusion and exclusion criteria. Demographic details, comorbid conditions, biochemical parameters, urine output system affection, renal replacement therapy (RRT) details, and fluid replacement were recorded. Outcome measures assessed were serum creatinine at transfer-out from ICU serum creatinine at discharge days of ICU stay and days of hospital stay death/ discharge and requirement of RRT after discharge. RESULT(S): 200 patients of AKI getting admitted to ICU were included in this study. Diabetes mellitus (19.5%) was the most common comorbidity. AKI was most seen in the post-surgery setting (33%), and severe non-surgical sepsis (37%). The most important risk factors predicting in-hospital mortality in AKI patients were hepatic dysfunction (HR-3.471, p = 0.001), septicemia (HR-3.342, p = 0.0001), age >60 years (HR-4.000, p = 0.026), higher baseline SOFA score (HR-1.107, p = 0.001), anemia (HR-0.879, p = 0.003), and reduced serum iron levels (HR- 0.982, p = 0.001). CONCLUSION(S): Presence of age >60 years, hepatic dysfunction, septicemia, higher baseline SOFA score, anemia, and reduced serum iron emerged to be the most important predictors of mortality among intensive care requiring AKI patients. The surgical AKI incidence was less due to lesser number of elective surgeries during the COVID pandemic.

Patient with Presumed Asthma Develops Flash Pulmonary Edema Secondary to Undiagnosed Cor Triatriatum

INTRODUCTION: A patient with presumed status asthmaticus, treated with beta-agonist and fluid resuscitation, developed flash pulmonary edema and respiratory failure in the setting of undiagnosed cor triatriatum. DESCRIPTION: A teen male with history of asthma developed dyspnea and chest pain at work. At a local emergency room (ER), he received albuterol, steroid, magnesium sulfate, and 2 liters (L) of fluid. Chest X-ray (CXR) and computed tomography of the chest were normal. He was transferred with a diagnosis of status asthmaticus. On exam in the pediatric ER, he had tachycardia, tachypnea and diffuse wheezing. He received albuterol 20mg/hour and 3L of fluid boluses over several hours. Despite improvement in wheezing, the patient had ongoing tachycardia and chest pain. He was placed on oxygen by high-flow nasal cannula. Repeat CXR exhibited new diffuse airspace opacities, and a focused cardiac ultrasound showed a hyperdynamic left ventricle (LV) with normal function. The patient began to expectorate pink frothy fluid, with hypoxemia, requiring intubation. Covid-19 PCR, Troponin-I and B-Type Natriuretic peptide were negative. An echocardiogram revealed a dilated left atrium (LA) with an echogenic membrane within the LA, separating the pulmonary venous chamber from the LA and restricting blood flow into the LV. The LV was small in size with normal function. The right heart was normal. These findings were consistent with diagnosis of cor triatriatum sinister, whereby the LA is divided into two compartments by a membrane that can variably obstruct flow into the LV. For this patient, treatment with beta-agonist caused tachycardia and decreased LV filling. Fluid resuscitation increased intravascular volume. This combination worsened obstruction of blood flow from the LA to the LV, leading to flash pulmonary edema, respiratory failure, and shock. In the ICU, the patient underwent diuresis, and the cor triatarium membrane was later surgically resected. DISCUSSION: Asthma is encountered commonly in children. Patients not responsive to treatment for respiratory distress should have alternative diagnoses considered. Multiple cognitive biases led to delayed recognition of cardiac etiology as the cause for this patient's respiratory failure, including anchoring bias with premature closure.