Patient Demographic & Admission DetailsPatient Name: Nodar TsartsidzeAge / DOB: 75 years (Born: July 22, 1950)Gender: MaleAdmission Date: July 13, 2026Chief Complaints: Rapid heart rate, fluttering sensation in the chest, anxiety, marked general weakness, easy fatigue, and fever up to 38.5°C.History of Present Illness (HPI)The patient is a 75-year-old male with a recently diagnosed CD20+ Chronic Lymphocytic Leukemia (CLL) (diagnosed approximately 1 month prior) who presents with acute onset tachyarrhythmia and fever.Three days prior to admission (July 10, 2026), he received immunotherapy with Rituximab (500 mg + 100 mg $\times$ 2 vials) along with Neutromax (30 mg $\times$ 3 vials). On July 12, 2026, he developed a fever peaking at 38.5°C accompanied by intense cardiac palpitations. He initially refused hospitalization but was brought to the emergency department on July 13 due to worsening weakness, persistent palpitations, and dyspnea.Past Medical History (PMH) & MedicationsComorbidities: Paroxysmal atrial fibrillation (diagnosed/cardioverted with amiodarone in September 2025), arterial hypertension, hypothyroidism, bilateral renal microlithiasis, and a history of cataracts.Home Medications: Triplixam ($5/1.25/5\text{ mg}$), Euthyrox ($150\ \mu\text{g}$), Milurit (Allopurinol, $300\text{ mg}$), Xarelto, Acyclovir ($200\text{ mg}$), Biseptol (Co-trimoxazole), Mirtazapine, Alprazolam, and Sevpram.Objective & Diagnostic FindingsPhysical ExaminationVitals: BP: 133/93 mmHg, HR: 129 bpm (irregularly irregular), RR: 21 breaths/min, $SpO_2$: 97% on room air. Temp: 36.4°C at presentation (after home antipyretics).Cardiovascular: Heart sounds are dull and arrhythmic.Abdomen: Soft, non-tender, with pronounced flatulence. No peripheral edema or focal neurological deficits.Key Laboratory Results (July 13, 2026)Complete Blood Count (CBC):WBC: $104 \times 10^3/\mu\text{L}$ (Severe leukocytosis with 69.7% lymphocytes, consistent with CLL)HGB: $13.3\text{ g/dL}$ (Mild anemia)PLT: $323 \times 10^3/\mu\text{L}$ (Normal)ESR: $30\text{ mm/hour}$ (Elevated)Arterial/Venous Blood Gas & Electrolytes:pH: 7.52 (Alkalemia)Sodium ($Na^+$): $123\text{ mmol/L}$ (Severe Hyponatremia)Potassium ($K^+$): $3.5\text{ mmol/L}$ (Low-normal)Ionized Calcium ($Ca^{++}$): $1.05\text{ mmol/L}$ (Hypocalcemia)Uric Acid: $163\ \mu\text{mol/L}$ (Normal/low, on Allopurinol prophylaxis)CRP: $0.68\text{ mg/dL}$ (Normal/minimally elevated)Imaging & DiagnosticsECG: Atrial Fibrillation with Rapid Ventricular Response (RVR) (HR ~129–150 bpm), left axis deviation.Echocardiography: Mild left atrial dilatation, concentric septal hypertrophy, and moderately impaired left ventricular systolic function (EF ~45%) with posterior/inferior wall hypokinesia.Abdominal Ultrasound: Mild hepatomegaly (154 mm), normal spleen size, and bilateral renal microlithiasis Give as case presentation with diagnosis and differential diagnosis with reasons and treatment plan
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CASE PRESENTATION
Patient: Nodar Tsartsidze | 75-year-old Male | Admitted: July 13, 2026
I. PRESENTING SUMMARY
A 75-year-old male with recently diagnosed CD20+ Chronic Lymphocytic Leukemia (CLL) - diagnosed approximately one month prior - presents to the Emergency Department with acute-onset tachyarrhythmia, fever, marked weakness, dyspnea, and chest palpitations. Three days prior, he received his first dose of anti-CD20 immunotherapy (Rituximab 600 mg total, split across two vials) combined with G-CSF (Neutromax/filgrastim 90 mg total). He developed fever to 38.5°C and intense palpitations the following day, initially refusing hospitalization. He was brought in on Day 3 due to worsening dyspnea and generalized weakness.
His background is significant for paroxysmal atrial fibrillation (cardioverted with amiodarone in September 2025), arterial hypertension, hypothyroidism, bilateral renal microlithiasis, and a history of cataract surgery.
II. DIAGNOSIS (PRIMARY & WORKING)
Primary Diagnosis:
Paroxysmal Atrial Fibrillation with Rapid Ventricular Response (RVR), newly relapsed - precipitated by multiple concurrent metabolic and pharmacologic triggers, in a patient with reduced LV systolic function (EF ~45%) and CLL on active immunotherapy.
Co-Diagnoses (all present simultaneously):
| # | Diagnosis | Key Supporting Evidence |
|---|---|---|
| 1 | AF with RVR (relapsed paroxysmal AF) | HR 129-150 bpm irregularly irregular; ECG confirms AF; prior history of paroxysmal AF cardioverted 2025 |
| 2 | Severe Hyponatremia (Na+ 123 mmol/L) | Lab confirmed; likely SIADH triggered by rituximab, CLL, or mirtazapine; major AF precipitant |
| 3 | Hypocalcemia (iCa++ 1.05 mmol/L) | Consistent with subclinical Tumor Lysis Syndrome (TLS) post-rituximab; Ca++ <1.12 mmol/L is below normal range |
| 4 | Metabolic Alkalosis (pH 7.52) | Likely from vomiting/fever + hyponatremia-related shifts |
| 5 | Post-Rituximab Infusion Syndrome / Cytokine Release | Fever 38.5°C, palpitations, weakness 24-48h post-infusion |
| 6 | Mild LV Systolic Dysfunction (EF ~45%) with posterior/inferior hypokinesia | Echo findings; likely undiagnosed or underappreciated prior to this presentation |
| 7 | CLL with marked leukocytosis (WBC 104 x 10³/µL, 69.7% lymphocytes) | Known diagnosis, confirmed by CBC |
III. PATHOPHYSIOLOGICAL REASONING
Why Did AF with RVR Occur Now?
This patient has four simultaneous arrhythmia-promoting conditions converging after rituximab administration:
1. Severe Hyponatremia (Na+ 123 mmol/L)
Hyponatremia alters the resting membrane potential of cardiomyocytes and atrial cells, destabilizing electrical conduction. Low sodium reduces atrial refractoriness and promotes ectopic atrial firing. The 2025 computational modeling literature (Corrado et al., Commun Med, PMID 41331342) directly confirms that clinically relevant changes in extracellular electrolyte concentrations alter human atrial arrhythmia dynamics.
Source of hyponatremia in this case:
- Rituximab-associated SIADH - monoclonal antibody infusion can trigger cytokine-mediated ADH release
- Mirtazapine - a well-established cause of SIADH/hyponatremia through serotonergic pathways (the most likely pharmacological contributor given ongoing use)
- CLL itself - paraneoplastic SIADH is recognized in B-cell malignancies
2. Hypocalcemia (iCa++ 1.05 mmol/L) - Subclinical Tumor Lysis Syndrome
Harrison's Principles (22E, 2025) states: "Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and is caused by the destruction of a large number of rapidly proliferating neoplastic cells." TLS is explicitly listed as a complication of rituximab in CLL patients with large tumor burden - and this patient's WBC of 104 x 10³/µL represents an enormous circulating tumor burden. Hypocalcemia shortens the action potential plateau and promotes early after-depolarizations, contributing to arrhythmia. The uric acid is paradoxically normal/low because allopurinol prophylaxis was appropriately prescribed - but this does not exclude TLS, as phosphate and calcium shifts can occur even with uric acid control.
3. Rituximab Cytokine Release / Infusion Reaction
Goodman & Gilman's notes: "Patients with large numbers of circulating tumor cells (as in CLL) are at increased risk for tumor lysis syndrome; in these patients, the initial dose should be no more than 50 mg/m² on day 1." Additionally, Fuster and Hurst's The Heart (15th Ed.) states: "The infusion of monoclonal antibodies commonly causes hypotension as a result of the massive release of cytokines (an acute transfusion reaction); these agents may also cause fever, dyspnea, hypoxia." The cytokine surge from rituximab directly elevates sympathetic tone, raises catecholamine levels, and increases heart rate - all powerful triggers of AF in a structurally vulnerable heart.
4. Pre-existing Structural Heart Disease
Echo demonstrates EF 45% (mildly-moderately reduced), posterior/inferior wall hypokinesia (suggesting prior ischemic injury or hypertensive cardiomyopathy), mild left atrial dilatation, and concentric septal hypertrophy. LA dilatation is the single most important structural substrate for AF. The wall hypokinesia raises the question of prior coronary artery disease (silent MI), and the low-normal potassium (3.5 mmol/L) further lowers the arrhythmia threshold.
IV. DIFFERENTIAL DIAGNOSIS
| Differential | Arguments FOR | Arguments AGAINST |
|---|---|---|
| 1. AF-RVR triggered by metabolic derangements (WORKING DX) | Na+ 123, iCa 1.05, pH 7.52; timing post-rituximab; prior AF history | - |
| 2. Sepsis/Infection-triggered AF | Fever 38.5°C at home; WBC elevation (though WBC reflects CLL); ESR 30 (mild elevation) | WBC elevation is from CLL lymphocytosis, not neutrophilia; CRP only 0.68 mg/dL (very low, making bacterial sepsis less likely); temp normal at presentation after antipyretics |
| 3. Tumor Lysis Syndrome (TLS) | Hypocalcemia, post-rituximab timing, massive WBC/tumor burden, renal microlithiasis as substrate for uric acid damage | Uric acid is low/normal (allopurinol working); no hyperkalemia; no hyperphosphatemia documented (should be ordered) |
| 4. Rituximab Infusion Reaction / Cytokine Release Syndrome (CRS) | Fever, palpitations, weakness 24-48h post-infusion; known mechanism | Fever could be from infection; severity is Grade 1-2 (mild CRS) rather than severe (no hypotension, SpO2 97%) |
| 5. Pulmonary Embolism | AF, tachycardia, dyspnea, recent immunocompromised/malignant state, on anticoagulation (Xarelto) | SpO2 97% on room air; no right heart strain on echo; on adequate anticoagulation |
| 6. ACS (Acute Coronary Syndrome) | Echo shows posterior/inferior hypokinesia; new LV dysfunction EF 45% | No chest pain described; no ST changes on ECG (AF with LVR pattern); no troponin result documented (should be ordered) |
| 7. Hypothyroid-triggered AF (Thyroid Storm equivalent) | On Euthyrox 150 µg; TSH/T4 not documented | No clinical signs of thyrotoxicosis; hypothyroidism more likely causes bradycardia, not AF with RVR |
| 8. Amiodarone toxicity / withdrawal | Used amiodarone previously; now not listed as current medication (stopped after cardioversion) | Amiodarone is not listed as a current medication; this is more likely a recurrence of paroxysmal AF without the maintenance agent |
| 9. Drug-induced AF (mirtazapine, alprazolam, sevpram/escitalopram) | Mirtazapine can prolong QTc; escitalopram can prolong QT; combination effect possible | These are chronic medications without dose change documented; less likely as sole trigger |
V. TREATMENT PLAN
Immediate Priorities (First 0-6 Hours)
A. Cardiac - Rate Control (NOT immediate cardioversion)
Per Braunwald's Heart Disease and Tintinalli's Emergency Medicine:
"In patients with systolic dysfunction, intravenous digoxin (in the absence of an accessory pathway), cautious use of beta blocker therapy, or amiodarone may be used. Diltiazem and other agents that suppress ventricular function should be avoided in patients with significant systolic dysfunction."
"In situations involving AF with rapid ventricular response and an active, significant underlying acute medical issue, management priority is focused on treating the underlying medical issue while not employing standard rate and rhythm control therapies in the early stages of care."
Given EF ~45% (borderline systolic dysfunction) and the presence of multiple metabolic triggers:
- Amiodarone IV is the preferred agent - provides rate control AND rhythm control, safe in reduced EF, and was effective in this patient previously. Katzung's notes: "In patients with atrial fibrillation, a rapid ventricular response, and heart failure, intravenous amiodarone is useful to control the ventricular response."
- Loading dose: 150 mg IV over 10 min, then 1 mg/min for 6h, then 0.5 mg/min
- Digoxin IV as second-line adjunct for rate control (0.25-0.5 mg IV slowly) - safe in reduced EF
- Avoid: Diltiazem, verapamil (calcium channel blockers) - contraindicated with EF 45%
- Avoid: High-dose beta-blockers IV - risk of hemodynamic compromise; if used, use with great caution at lowest dose
- Electrical cardioversion: Not indicated unless hemodynamically unstable (BP currently 133/93 mmHg - currently stable). The underlying metabolic triggers must be corrected first, or cardioversion will fail or rapidly recur.
B. Anticoagulation
- Patient is already on Xarelto (rivaroxaban) - continue
- CHA₂DS₂-VASc score estimation: Age 75 (2) + male (0) + hypertension (1) + heart failure/reduced EF (1) + prior AF = score ≥4 → anticoagulation clearly indicated and already in place
- Confirm last dose timing before any cardioversion consideration
Metabolic Correction (Parallel Priority)
C. Severe Hyponatremia (Na+ 123 mmol/L)
This is symptomatic hyponatremia (weakness, arrhythmia, altered physiology) at a critically low level.
Per Rosen's Emergency Medicine:
"The mainstay of treatment of euvolemic hyponatremia is free water restriction... If a patient is symptomatic because of a rapid decrease in serum sodium concentration, treatment with hypertonic saline is recommended."
- Hypertonic saline (3% NaCl) if symptomatic - bolus 100-150 mL IV over 20 minutes, targeting a rise of 4-6 mEq/L in the first 1-2 hours, then slow correction
- Target correction rate: No more than 8-10 mEq/L per 24 hours (maximum 12 mEq/L/24h) to prevent osmotic demyelination syndrome (central pontine myelinolysis)
- Fluid restriction: 500-800 mL/24h if euvolemic SIADH suspected
- Monitor serum Na+ every 2-4 hours
- STOP mirtazapine - a likely contributor to SIADH; needs psychiatric/geriatric re-evaluation for safer alternative
- Evaluate volume status clinically (urine sodium, urine osmolality, clinical exam) to distinguish SIADH from hypovolemic hyponatremia
D. Hypocalcemia (iCa++ 1.05 mmol/L) - Probable TLS Component
- Calcium gluconate 1-2 g IV over 10-20 minutes (especially with arrhythmia present)
- Repeat ionized calcium monitoring every 4-6 hours
- Check serum phosphate - if elevated, confirms TLS; aggressive phosphate restriction
- Continue allopurinol (already prescribed as Milurit 300 mg) - appropriate TLS prophylaxis
- Monitor: K+, phosphate, uric acid, creatinine, LDH (TLS panel) every 6-8 hours
- IV hydration at 2-3 L/day (unless cardiac compromise worsens) to protect kidneys and promote uric acid excretion
E. Potassium Repletion
- K+ 3.5 mmol/L is low-normal but borderline in the context of arrhythmia - target >4.0 mmol/L
- Oral or IV KCl supplementation 20-40 mEq/day
- Magnesium status should also be checked and repleted if low (magnesium deficiency commonly co-exists and worsens AF)
Infection / CRS Workup
F. Rule Out Bacterial/Opportunistic Infection
Despite very low CRP (0.68 mg/dL), fever must be investigated in an immunocompromised CLL patient on rituximab:
- Blood cultures x 2 sets (peripheral + central if available)
- Urinalysis + urine culture
- Chest X-ray (fever + dyspnea + WBC in immunocompromised)
- Consider CT chest if CXR abnormal or high clinical suspicion for pneumonia (PCP given Biseptol prophylaxis is already prescribed - suggests known immunocompromise awareness)
- The existing Biseptol (co-trimoxazole) and Acyclovir suggest the treating oncology team was already prophylaxing against PCP and herpes reactivation - appropriate
G. CRS Management
- Grade 1-2 CRS (fever, palpitations, no hypotension, SpO2 97%): supportive treatment
- Acetaminophen/paracetamol for fever control
- Antihistamines (diphenhydramine or chlorphenamine) for infusion reaction component
- Dexamethasone/prednisolone IV if CRS progresses to Grade 2-3 (fever >38°C refractory, hemodynamic instability)
- No further rituximab until patient is hemodynamically and metabolically stable; next cycle dose should be reduced to 50 mg/m² as per Goodman & Gilman's recommendation for CLL patients with high tumor burden
Additional Investigations (Urgent Orders)
| Test | Reason |
|---|---|
| Troponin I/T (serial x 2) | Posterior/inferior hypokinesia on echo; rule out ACS |
| BNP or NT-proBNP | Quantify HF severity, guide therapy |
| Serum phosphate | TLS completion panel |
| LDH | TLS severity marker |
| Magnesium | Co-factor in AF and electrolyte balance |
| TSH + Free T4 | Hypothyroidism control on Euthyrox 150 µg; exclude thyroid-triggered AF |
| Serum creatinine + BUN | Renal function baseline; TLS-related nephropathy |
| Prothrombin time / INR (if Xarelto timing unclear) | Pre-cardioversion if needed |
| Urine Na+, urine osmolality, urine creatinine | Differentiate SIADH from hypovolemic hyponatremia |
| Repeat ECG after rate control | Assess for ischemic changes hidden behind rapid AF |
Monitoring Parameters
- Continuous cardiac monitoring (telemetry)
- Vitals Q1h until rate controlled, then Q4h
- Strict fluid balance (input/output chart)
- Serial serum Na+ every 2-4 hours while on hypertonic saline correction
- Daily TLS panel until resolution
- Repeat echo in 48-72h if EF does not improve
Medication Review / Adjustments
| Medication | Recommendation |
|---|---|
| Xarelto | Continue - anticoagulation indicated |
| Triplixam (perindopril/amlodipine/indapamide) | Indapamide component can worsen hyponatremia - HOLD indapamide-containing component; continue ACE inhibitor component with caution |
| Euthyrox 150 µg | Continue; check TSH |
| Milurit (allopurinol 300 mg) | Continue - TLS prophylaxis critical |
| Acyclovir 200 mg | Continue - viral prophylaxis in immunocompromised state |
| Biseptol (co-trimoxazole) | Continue - PCP prophylaxis |
| Mirtazapine | HOLD - likely contributor to SIADH/hyponatremia |
| Sevpram (escitalopram) | Review - SSRIs can cause SIADH; hold or switch |
| Alprazolam | Reduce if possible in acute setting; benzodiazepine dependence risk in elderly |
| Amiodarone (new IV) | Add for AF rate/rhythm control |
| Neutromax (G-CSF) | Assess necessity - G-CSF can promote cytokine release; discuss with oncology |
Admission Disposition
Admit to Cardiac Monitoring Unit (CCU or Step-Down) given:
- Hemodynamically significant arrhythmia (AF-RVR HR 129-150)
- Severe symptomatic hyponatremia (Na+ 123)
- Hypocalcemia with arrhythmia substrate
- Reduced LV function (EF 45%)
- Post-immunotherapy cytokine release / TLS risk
- Age 75, multiple comorbidities, polypharmacy
Multidisciplinary team: Cardiology + Hematology/Oncology + Nephrology (for hyponatremia management) + Pharmacy (drug interaction review)
VI. PROGNOSIS & CLINICAL NOTES
This is a high-risk presentation with multiple intersecting pathologies. The AF-RVR is likely to be self-limiting once the metabolic derangements (hyponatremia, hypocalcemia) are corrected and the cytokine storm from rituximab infusion subsides - consistent with the concept of "complex AF" described in Tintinalli's, where treatment of the underlying trigger takes priority over aggressive antiarrhythmic therapy. The posterior/inferior wall hypokinesia and EF 45% represent a potentially important incidental finding that warrants outpatient coronary workup once the patient is stabilized.
The ongoing oncologic management of CLL with Rituximab should be continued but with dose adjustment (capped at 50 mg/m² for future cycles given the extreme lymphocytosis), adequate pre-medication (antihistamine + steroid + acetaminophen), and inpatient monitoring for the first infusion of each subsequent cycle.
Sources: Braunwald's Heart Disease (10th Ed.), Tintinalli's Emergency Medicine (9th Ed.), Harrison's Principles of Internal Medicine (22nd Ed., 2025), Goodman & Gilman's Pharmacological Basis of Therapeutics, Rosen's Emergency Medicine, Fuster and Hurst's The Heart (15th Ed.), Corrado et al. Commun Med 2025 (PMID 41331342).
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