Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction

Breathlessness can occur in a number of autonomic conditions, often in the form of dysfunctional breathing. The exact mechanism remains uncertain, but reduced perfusion of blood pressure receptors and chemoreceptors in the carotid sinus and carotid body, leading to hyperventilation, is postulated. This is recognised to occur in vasovagal syncope and in cases of significant autonomic dysfunction. It also occurs in PoTS, a condition predominantly affecting young women and often precipitated by another illness and increasingly by coronavirus disease 2019. It is characterised by cardiovascular and respiratory symptoms when upright, is relieved by recumbency and is associated with a significant heart rate increase. Other autonomic symptoms of organ dysfunction can occur, in the gastrointestinal and genitourinary system for example. There are guidelines and therapies that can produce significant symptomatic improvements, but maintaining a high level of suspicion for the diagnosis is important, as it can easily be overlooked.Copyright © ERS 2021.

A CASE OF TRACHEOBRONCHIAL AMYLOIDOSIS PRESENTING AS SYNCOPE

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Amyloidosis of the respiratory tract is rare. We present a case of tracheobronchial amyloid presenting as multifactorial cough with syncope. CASE PRESENTATION: The patient is a 65-year-old man with history of hypertension, hyperlipidemia, and allergic rhinitis who presented to the ED after a syncopal event. Two weeks prior, he had a new-onset myalgias and severe persistent cough, not resolving with over-the-counter medications. During a coughing paroxysm, he experienced a brief loss of consciousness. On arrival, his vital signs and physical exam were within normal limits except for Mallampati II, BM of 38.8 kg/m2. Basic laboratory testing was also unremarkable except for troponin T of 251 nl/dL and NT-ProBNP of 1181 pg/mL. NP swab for Sars-CoV-19 (PCR), Influenza A and B were not detected. CT of the chest revealed an area of circumferential mural soft tissue thickening in the left lower lobe bronchi. Cardiac MRI showed an area of subepicardial delayed enhancement, suggestive of myocardial inflammation or edema. Flexible bronchoscopy confirmed that the left lower lobe bronchus and proximal subsegmental bronchi had an infiltrative process with a friable, erythematous irregular mucosal surface. Forceps biopsy sampling and staining with Congo red, sulfate Alcian blue and Trichome stain were positive for amyloid deposits. Immunostain revealed predominantly CD3 positive T-Cells. Mass spectometry showed AL (lamda)-type amyloid deposition. GMS and AFB stains were negative. Telemetry showed 2-3 second pauses, correlated with episodes of cough. DISCUSSION: Amyloidosis is a disorder caused by misfolding of proteins and fibril accumulation in the extracellular space. It can present as a diffuse or localized process to one organ system. Several patterns of lung involvement have been described: nodular pulmonary, diffuse alveolar-septal, cystic, pleural, and tracheobronchial amyloidosis. Tracheobronchial amyloidosis is usually limited and not associated with systemic disease or hematologic malignancy. It can be asymptomatic, or can present with cough, dyspnea or signs of obstruction, including postobstructive pneumonia. Congo Red stained samples reveal green birefringence under polarized light microscopy. Further analysis of proteins usually reveals localized immunoglobulin light chains (AL). Cough syncope is due to increased intrathoracic pressure, decreased venous return and cardiac output, stimulation of baroreceptors, decreased chronotropic response, arterial hypotension and decreased cerebral perfusion. Our patient presented with multifactorial cough (possible viral infection, upper airway cough syndrome, amyloidosis) causing sinus pauses and syncope, on underlying myocarditis. CONCLUSIONS: Amyloid infiltration of the respiratory system is rare, but it should be considered in the differential diagnosis of airway disorders, nodular or cystic lung diseases, and pleural processes. Reference #1: Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev 2017;26: 170046 [https://doi.org/10.1183/16000617.0046-2017]. Reference #2: Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996 Feb 15;124(4):407-13. doi: 10.7326/0003-4819-124-4-199602150-00004 Reference #3: Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014 Feb;108(2):244-51. doi: 10.1016/j.rmed.2013.10.020. Epub 2013 Nov 5. PMID: 24238768. DISCLOSURES: No relevant relationships by Amarilys Alarcon-Calderon No relevant relationships by Ashokakumar Patel

COVID-19-INDUCED POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is one of the most common autonomic disorders (1). POTS is diagnosed by increasing heart rate by 30 bpm on more, within the first 10 minutes of standing, without orthostatic hypotension (2). Associated debilitating symptoms are lightheadedness, fainting, tremor, orthostatic intolerance, and tachycardia (2). Viral infections such as HIV, hepatitis C, mumps, Epstein bar virus, and influenza have been commonly reported with POTS syndrome (3 ). We are presenting a rare case of COVID-19 induced POTS. CASE PRESENTATION: 38-year-old presented to the hospital with the chief complaint of shortness of breath chest tightness. Her past medical history was significant for COVID-19 infection two weeks before presentation. On arrival patient's vitals were within normal limits. Her physical examination was unremarkable. Laboratory investigations, including complete blood count, thyroid function test, and comprehensive metabolic profile, were unremarkable. Chest x-ray, CT angiogram, and echocardiogram were unremarkable for any consolidation, pulmonary embolism, and congestive heart failure. Orthostatic vitals were obtained, showing that the patient's heart rate increased from 90 beats/minute to 140 beats/minute, from supine to standing. This patient was diagnosed with COVID-19 induced POTS, given she was meeting the criteria of POTS and no other reason was found for postural orthostatic tachycardia. She was managed conservatively with hydration, and the patient was also instructed about yoga therapy. She was discharged home with a cardiology follow-up. DISCUSSION: COVID-19 induced POTS is a relatively new entity that most commonly affect female, and the estimated prevalence is around is 17 per 100,000 patients (3). It has been reported that 10% of the patient who tests positive for COVID-19 infection remains unwell beyond three weeks after recovery from the infection (2). For some of those patients, POTS may be the cause of their symptoms. The exact pathophysiology for COVID-19 induced POTS is poorly understood and may includes peripheral neuropathy, baroreceptor dysfunction, hypovolemia, and increased serum norepinephrine (2). Nonpharmacological treatment includes increasing fluid consumption of 2 to 3 L of water per day, lower limb compression stockings, and regular exercise (2). The commonly off-label pharmacological treatment include ivabradine, fludrocortisone, midodrine, and beta-blockers (2). CONCLUSIONS: POTS is a new and under-recognized entity. The clinician should have a high suspicion of POTS syndrome in a patient with a history of recent or remote COVID-19 infection presenting with orthostatic symptoms. Timely diagnosis is essential to prevent the morbidity associated with debilitating symptoms. Reference #1: Blitshteyn S & Whitelaw S. Postural Orthostatic Tachycardia Syndrome (POTS) and Other Autonomic Disorders After COVID-19 Infection: A Case Series of 20 Patients. Immunol Res. 2021;69(2):205-11. Reference #2: Jenna Stephanie O'Sullivan, Andrew Lyne, Carl J Vaughan. COVID-19-Induced Postural Orthostatic Tachycardia Syndrome Treated with Ivabradine. BMJ Case Reports CP. 2021;14(6):e243585. Reference #3: Sujana Reddy, Satvik Reddy, Manish Arora. A Case of Postural Orthostatic Tachycardia Syndrome Secondary to the Messenger RNA COVID-19 Vaccine. Cureus. 2021;13(5). DISCLOSURES: No relevant relationships by Arshan Khan

THE BIG IMPACT OF SMALL CHANGES IN NARROW THERAPEUTIC INDEX DRUGS

CASE: An 84-year-old woman with atrial fibrillation on Digoxin presented with acute onset of confusion associated with a week history of abdominal pain, vomiting, and poor fluid intake. A few days prior, Amiodarone was added to her drug regimen which included Lasix. Additionally, she received the COVID-19 booster vaccine which led to a viral-like syndrome resulting in dehydration. The patient was afebrile, normotensive, but bradycardic. EKG showed a prolonged PR interval and scooped ST segments. Labs showed hyperkalemia, pre-renal acute kidney injury (AKI), and a Digoxin level of 4.3 ng/mL (therapeutic range: 0.8-2.0 ng/mL). Digoxin and Lasix were held and Digoxin antidote, Digibind, was administered with normalizing heart rate, potassium, and clinical improvement. IMPACT/DISCUSSION: Digoxin is used to slow conduction in atrial fibrillation and increase cardiac contractility in heart failure. It inhibits the membrane sodium-potassium-adenosine triphosphatase pump (Na/K ATPase), resulting in increased cytosolic calcium and subsequent cardiac contractility and automaticity. In turn, this can also cause premature ventricular contractions and tachycardia. In the carotid sinus, increased baroreceptor firing and subsequent increased vagal tone occurs which can cause bradycardia, atrioventricular blocks, hypotension, and GI symptoms. In skeletal muscle, hyperkalemia can result due to the abundance of Na/K ATPase pumps. Digoxin has a narrow therapeutic index with serum levels easily affected by many commonly prescribed drugs by way of decreasing renal clearance, inhibiting P-glycoprotein, and inducing secondary electrolyte disturbances. That said, drug dosing should be individualized with close monitoring to avoid potentially life-threatening effects that may result with even mildly increased digoxin levels. Acute toxicity manifests as non-specific GI, and neurologic symptoms (confusion, lethargy, visual changes), hyperkalemia, and brady or tachy-arrhythmias. Treatment is with digoxin specific fragment antigen binding (Fab) antibody, Digibind, which binds digoxin, inactivating it within 6-8 hours. Postadministration, digoxin serum testing cannot distinguish free verse bound drug;therefore, drug levels remain elevated for days to weeks until the FabDigoxin complex is excreted. In the case above, the viral-like-syndrome after the booster vaccine with subsequent AKI secondary to dehydration likely precipitated Digoxin toxicity. Accompanying drug interactions of diuretics causing dehydration and hypokalemia, P-glycoprotein inhibitors (Amiodarone, Verapamil, Diltiazem, Quinidine), and ACE inhibitors can further worsen renal clearance and culminate in Digoxin toxicity. CONCLUSION: Given Digoxin's narrow therapeutic index, small clinical changes such as post COVID-19 vaccine flu-like symptoms, dehydration, and medication changes can manifest drug toxicity. Therefore, attentive monitoring of accompanying comorbidities and drug interactions is imperative at preventing catastrophic toxic effects.

Syncope at SARS-CoV-2 onset.

We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) indicating hypocapnic hypoxemia. Patients who presented with syncope showed significantly lower heart rate as compared to 68 SARS-CoV-2 positive that did not. Such poorer than expected compensatory heart rate increase may have led to syncope based on individual susceptibility. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.