What could be the cause of sudden onset palpitations and uneasiness with desaturation in a patient with Diabetes Mellitus (DM), Hypothyroidism, Hypertension (HT), Atrial Fibrillation (AF) with Controlled Ventricular Rate (CVR), Heart Failure with preserved Ejection Fraction (HFpEF), Diabetic Kidney Disease (DKD), and history of Colorectal Cancer (CRC) with metastases to the liver, post-surgical excision and chemotherapy?

Differential Diagnosis: Sudden Palpitations with Desaturation in Complex Medical Patient

In this patient with multiple cardiovascular comorbidities and recent cancer treatment, the most likely causes are acute decompensation of atrial fibrillation with rapid ventricular response, pulmonary embolism (given cancer history and desaturation), or chemotherapy-induced arrhythmia—with immediate ECG, cardiac monitoring, and assessment for hemodynamic stability being critical first steps.

Immediate Life-Threatening Considerations

Pulmonary Embolism

• Cancer with liver metastases creates a profoundly prothrombotic state, making PE a leading concern when desaturation accompanies palpitations 1
• Post-chemotherapy patients have markedly elevated thrombotic risk, particularly with colorectal cancer and hepatic involvement 1
• The combination of palpitations (from right heart strain/sinus tachycardia) plus desaturation is classic for PE in this population 1

Acute AF with Rapid Ventricular Response

• This patient has known AF, and sudden loss of rate control can cause both palpitations and desaturation from reduced cardiac output 2
• HFpEF patients are particularly vulnerable to hemodynamic compromise with rapid AF due to dependence on atrial kick for ventricular filling 3
• Chemotherapy drugs including 5-fluorouracil, doxorubicin, and cisplatin are all associated with AF exacerbation 1

Ventricular Arrhythmias

• Cancer patients have a 10-fold increase in ventricular arrhythmia burden after diagnosis, with stage IV cancer (metastatic disease) conferring highest risk 1
• Chemotherapy-induced QT prolongation can precipitate torsades de pointes, presenting with palpitations and hemodynamic compromise 1
• Multiple medications in this patient (for bipolar disorder, potentially antiemetics from chemo) may prolong QT interval 1

Chemotherapy-Related Cardiac Complications

Drug-Induced Arrhythmias

• Older age, pre-existing cardiovascular disease (HT, HFpEF, AF, DKD), and baseline ECG abnormalities are all risk factors for chemotherapy-induced arrhythmias 1
• Colorectal cancer chemotherapy regimens typically include 5-fluorouracil, which causes AF, ventricular arrhythmias, and coronary vasospasm 1
• Electrolyte abnormalities from chemotherapy-induced nausea/vomiting/diarrhea are common precipitants of arrhythmias 1

Cardiac Decompensation

• Chemotherapy can cause direct myocardial injury leading to acute HF exacerbation, manifesting as palpitations and desaturation 1
• Anthracyclines (if used) cause cardiomyopathy with increased arrhythmia risk, particularly in patients with pre-existing HFpEF 1

Metabolic and Medication Factors

Electrolyte Disturbances

• DKD predisposes to potassium and magnesium abnormalities, both critical arrhythmia triggers 1
• Post-chemotherapy patients frequently have hypokalemia and hypomagnesemia from GI losses 1
• Hypothyroidism medications require monitoring as thyroid dysfunction itself causes arrhythmias 1

Drug-Drug Interactions

• Bipolar disorder medications (particularly antipsychotics) can prolong QT interval and interact with chemotherapy agents 1
• Multiple QT-prolonging agents (antiemetics like ondansetron, psychiatric medications, chemotherapy) create additive risk 1

HFpEF-Specific Considerations

Acute Decompensation

• Diabetes with HFpEF causes pronounced left ventricular hypertrophy and diastolic dysfunction, making patients extremely sensitive to rate/rhythm changes 4
• AF with rapid rate in HFpEF patients causes immediate pulmonary congestion and desaturation due to elevated left atrial pressures 3
• Diabetic microvascular disease in HFpEF patients leads to greater LV remodeling and worse outcomes with arrhythmias 5

Critical Diagnostic Approach

Immediate Assessment Required

• 12-lead ECG to identify rhythm (AF with RVR, VT, or QT prolongation) 6, 2
• Continuous cardiac monitoring for arrhythmia detection 1
• Oxygen saturation and arterial blood gas to quantify hypoxemia 1
• Troponin and BNP to assess for acute coronary syndrome or HF decompensation 1

Urgent Investigations

• Comprehensive metabolic panel including potassium, magnesium, calcium, and renal function 1
• D-dimer and CT pulmonary angiography if PE suspected (though D-dimer has limited utility in cancer patients) 1
• Echocardiography to assess ventricular function and rule out new wall motion abnormalities 1
• Review all medications for QT-prolonging agents and potential drug interactions 1

Management Priorities

Hemodynamic Instability

• If hemodynamically unstable with any arrhythmia, immediate synchronized cardioversion is indicated 6
• For suspected torsades de pointes: 2g IV magnesium regardless of serum level, discontinue QT-prolonging drugs 1

Stable Arrhythmia Management

• For AF with RVR: rate control with beta-blockers or calcium channel blockers, avoiding agents with significant drug interactions 1
• Correct all electrolyte abnormalities before antiarrhythmic therapy 1
• Anticoagulation decisions in cancer patients with AF require balancing thrombotic risk (elevated) against bleeding risk from chemotherapy-induced thrombocytopenia 1

PE Management

• If PE confirmed, therapeutic anticoagulation with consideration of cancer-associated thrombosis protocols 1

Key Clinical Pitfalls

• Do not assume palpitations are simply AF exacerbation without ECG confirmation—VT is common in metastatic cancer 1
• Desaturation with palpitations mandates PE exclusion in any cancer patient 1
• Multiple QT-prolonging medications are ubiquitous in cancer patients (chemotherapy, antiemetics, psychiatric drugs)—always check QTc 1
• HFpEF patients with diabetes are exquisitely sensitive to rhythm disturbances and rapidly decompensate 4
• Cancer patients require hospitalization for evaluation when VA is documented or suspected 1