What is the likely cause of a 60-year-old patient's symptoms of fatigue, nocturia, and decreased sleep quality, with a history of hypertension, Class 2 heart failure, and recent use of Naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)), presenting with elevated N-terminal pro b-type natriuretic peptide (NT-proBNP), troponin I, hyperkalemia, impaired renal function (eGFR), and reduced ejection fraction on echocardiogram?

Likely Cause of Patient's Symptoms

The patient's heart failure exacerbation is primarily caused by NSAID use (Naproxen), which has precipitated acute decompensation through sodium and fluid retention, worsening renal function, and interference with her ACE inhibitor therapy, compounded by medication non-adherence. 1

Primary Precipitating Factors

NSAID-Induced Heart Failure Exacerbation

• Naproxen 500 mg BID for 2 weeks is directly contraindicated in heart failure patients and causes fluid retention, edema, and worsening of pre-existing hypertension, all of which contribute to increased cardiovascular events 1
• NSAIDs impair the response to loop diuretics and ACE inhibitors, rendering her current heart failure regimen less effective 1
• The FDA label explicitly warns that NSAIDs should be used with extreme caution in patients with fluid retention, hypertension, or heart failure 1
• Her clinical presentation of nocturia, fatigue, bilateral crackles, S3 gallop, JVP elevation (4.2 cm), and new pedal edema directly correlates with the 2-week timeline of NSAID use 1

Medication Non-Adherence

• Patient admits to forgetting medications "on several occasions," which compromises the efficacy of her ACE inhibitor and beta-blocker therapy 2
• The 2016 ESC guidelines emphasize that every attempt should be made to continue evidence-based disease-modifying therapies in worsening chronic HFrEF 2

Supporting Laboratory and Diagnostic Evidence

Biomarker Profile Indicating Acute Decompensation

• NT-proBNP of 250 pg/mL is elevated (normal <125 pg/mL for age <75) and indicates cardiac stress, though the elevation is modest 2
• BNP of 125 pg/mL is also elevated (normal <100 pg/mL), confirming volume overload 2
• Troponin I of 0.02 ng/mL is within normal limits (<0.04 ng/mL), suggesting this is not an acute coronary syndrome but rather a hemodynamic decompensation 3

Renal Dysfunction Secondary to Cardiorenal Syndrome

• Creatinine 160 µmol/L (normal 49-90 µmol/L for females) and eGFR 45 mL/min/1.73m² indicate Stage 3b chronic kidney disease 2
• This renal impairment is likely multifactorial: chronic cardiorenal syndrome from longstanding heart failure, acute worsening from NSAID use, and ACE inhibitor therapy 1
• Hyperkalemia (5.4 mmol/L, normal 3.5-5.0 mmol/L) reflects reduced renal potassium excretion and ACE inhibitor effect 2

Hyponatremia and Volume Overload

• Sodium 130 mmol/L (normal 135-145 mmol/L) indicates dilutional hyponatremia from volume overload and neurohormonal activation 2
• This finding correlates with disease severity and worse prognosis in heart failure 2

Echocardiographic Deterioration

• Ejection fraction has declined from 50% (HFmrEF) to 38% (now HFrEF), representing significant progression of left ventricular systolic dysfunction 4
• This reclassification from heart failure with mid-range EF to reduced EF mandates immediate optimization of guideline-directed medical therapy 2, 4
• Chest X-ray showing cardiomegaly and pulmonary edema confirms acute volume overload 2

Physical Examination Findings

• S3 gallop indicates elevated left ventricular filling pressures and volume overload 2
• Laterally displaced PMI (6th ICS, 2.5 cm left of MCL) confirms left ventricular dilatation 4
• Bilateral fine crackles in lower lung fields indicate pulmonary congestion 2
• JVP 4.2 cm above sternal angle at 45 degrees indicates elevated right atrial pressure 2
• 1+ pitting pedal edema bilaterally confirms systemic venous congestion 2
• Blood pressure 150/90 mmHg represents inadequate hypertension control, worsened by NSAID use 1

Clinical Pitfalls to Avoid

Common Misattribution

• Do not attribute symptoms solely to urinary tract infection or primary sleep disorder—the nocturia is cardiac in origin (paroxysmal nocturnal dyspnea equivalent) 2
• The "difficulty staying asleep after a few hours" represents orthopnea/paroxysmal nocturnal dyspnea, not primary insomnia 2
• Morning fatigue reflects nocturnal pulmonary congestion and poor sleep quality from cardiac dyspnea 2

NSAID Recognition Gap

• Many patients and providers underestimate the cardiovascular risks of over-the-counter NSAIDs 1
• Even short-term NSAID therapy (2 weeks in this case) carries significant risk in heart failure patients 1
• The temporal relationship between NSAID initiation and symptom onset is diagnostically critical 1

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Consultation and Referral Indications

Immediate Cardiology Consultation Required

Worsening Ejection Fraction

• EF decline from 50% to 38% mandates urgent cardiology evaluation for optimization of guideline-directed medical therapy and consideration of device therapy 2, 4
• The 2016 ESC guidelines recommend that patients with HFrEF and LVEF ≤35% should be evaluated for ICD and CRT-D therapy 2
• While this patient is currently at 38%, the trajectory of decline and symptomatic deterioration warrant specialist assessment 2

Refractory Symptoms Despite Outpatient Management

• If symptoms do not improve within 48-72 hours of diuretic initiation and NSAID cessation, cardiology consultation is indicated 2
• Persistent dyspnea, worsening renal function, or inability to achieve euvolemia require specialist input 2

Nephrology Consultation Considerations

Progressive Renal Dysfunction

• eGFR 45 mL/min/1.73m² with hyperkalemia (5.4 mmol/L) requires careful monitoring 2
• If creatinine rises >30% from baseline or hyperkalemia worsens (>5.5 mmol/L) despite NSAID cessation and diuretic therapy, nephrology consultation is warranted 2
• The combination of ACE inhibitor therapy and declining renal function may require specialist guidance for medication titration 2

Electrophysiology Referral

Device Therapy Evaluation

• Once medically optimized, if EF remains ≤35% after 3 months of guideline-directed medical therapy, refer for ICD evaluation 2
• If QRS duration ≥130 msec with LBBB morphology, CRT-D should be considered 2

Emergency Department Transfer Criteria

Signs of Cardiogenic Shock

• Systolic BP <90 mmHg with signs of hypoperfusion 2
• Altered mental status, cool extremities, or oliguria 2
• Acute pulmonary edema with respiratory distress requiring non-invasive ventilation 2

Acute Coronary Syndrome

• New chest pain with dynamic ECG changes or troponin elevation 2
• Although current troponin is normal, serial monitoring is essential if ischemic symptoms develop 2

Life-Threatening Arrhythmias

• Sustained ventricular tachycardia, ventricular fibrillation, or high-grade AV block 2
• New-onset atrial fibrillation with rapid ventricular response and hemodynamic compromise 2

Severe Electrolyte Disturbances

• Potassium >6.0 mmol/L or <3.0 mmol/L with ECG changes 2
• Sodium <125 mmol/L with neurological symptoms 2

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Diuretic Prescription

Recommended Prescription

Furosemide 40 mg PO once daily

• Indication: Acute decompensated heart failure with volume overload (pulmonary edema, peripheral edema, elevated JVP) 2
• Duration: 5-7 days with close follow-up 2
• Instructions: Take in the morning to avoid nocturia. Weigh yourself daily at the same time. Call if weight increases >2 kg in 3 days or if shortness of breath worsens 2
• Monitoring: Follow-up in 3-5 days to assess clinical response, weight loss, and renal function/electrolytes 2

Rationale for Furosemide Selection

• Loop diuretics are recommended to reduce signs and symptoms of congestion in patients with HFrEF 2
• The 2016 ESC guidelines state that diuretics should be used to achieve and maintain euvolemia with the lowest achievable dose 2
• Starting dose of 40 mg is appropriate for this patient who is not currently on diuretic therapy and has moderate volume overload 2

Critical Concurrent Actions

• Immediately discontinue Naproxen 1
• Reinforce medication adherence for Metoprolol and Enalapril 2
• Provide alternative analgesia for knee pain (acetaminophen up to 3 g/day, avoiding NSAIDs) 1

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Lifestyle Modifications in Heart Failure

Dietary Sodium Restriction

• Limit sodium intake to <2-3 grams per day to reduce fluid retention and congestion 2
• The 2016 ESC guidelines recommend moderate sodium restriction in all symptomatic heart failure patients 2
• Patient admits to "sometimes cheating" on healthy eating—specific education on reading food labels and avoiding processed foods is essential 2

Fluid Management

• Restrict fluid intake to 1.5-2 liters per day in patients with severe heart failure or hyponatremia 2
• Given her sodium of 130 mmol/L, fluid restriction to 1.5 L/day is appropriate 2
• Teach patient to monitor daily weights and adjust diuretic dose based on weight changes 2

Smoking Cessation

• Immediate smoking cessation is mandatory—she has a 50-pack-year history (2 packs/day × 25 years) 2
• Smoking increases cardiovascular risk, worsens endothelial dysfunction, and accelerates heart failure progression 2
• Refer to smoking cessation program with consideration of pharmacotherapy (varenicline or bupropion) and nicotine replacement 2

Alcohol Limitation

• Limit alcohol to ≤1 standard drink per day for women 2
• Her "occasional draft beer" is acceptable if truly occasional, but should be quantified and limited 2
• Excessive alcohol can cause cardiomyopathy and worsen existing heart failure 2

Exercise Prescription

• Regular aerobic exercise is recommended to improve functional capacity, symptoms, and reduce HF hospitalization risk 2
• The 2016 ESC guidelines give a Class I, Level A recommendation for regular aerobic exercise in stable HFrEF patients 2
• Her current 1-mile daily walk is appropriate, but temporarily reduce intensity during acute decompensation 2
• Once euvolemic and stable, gradually return to baseline activity with goal of 30 minutes moderate-intensity exercise 5 days per week 2
• Cardiac rehabilitation referral should be considered 2

Weight Monitoring

• Daily weight measurement at the same time each morning after urination, before breakfast 2
• Contact provider if weight gain >2 kg in 3 days or >2.5 kg in 1 week 2
• Current weight 71 kg—target is to reduce by 2-3 kg to achieve euvolemia 2

Vaccination

• Annual influenza vaccination and pneumococcal vaccination are recommended to prevent infections that can precipitate heart failure exacerbations 2

Medication Adherence Strategies

• Use pill organizers, smartphone reminders, or medication synchronization programs 2
• Enroll in multidisciplinary heart failure management program to reduce hospitalization and mortality risk 2
• The 2016 ESC guidelines give a Class I, Level A recommendation for multidisciplinary care management 2

Avoid Nephrotoxic and Cardiotoxic Substances

• Absolute avoidance of NSAIDs (including over-the-counter ibuprofen, naproxen, aspirin >325 mg/day) 1
• Avoid decongestants containing pseudoephedrine or phenylephrine (increase BP and heart rate) 1
• Limit caffeine intake as it may exacerbate arrhythmias 2

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Medication Optimization for HFrEF (EF 38%)

Based on the echocardiogram showing EF 38% (now HFrEF) and elevated BNP/NT-proBNP, this patient requires immediate optimization of guideline-directed medical therapy with addition of multiple disease-modifying agents. 2, 4

Mandatory Medication Additions

1. Mineralocorticoid Receptor Antagonist (MRA)

• Add Spironolactone 12.5-25 mg PO daily 2
• The 2016 ESC guidelines give a Class I recommendation for MRAs in all symptomatic patients with HFrEF and LVEF ≤35% despite treatment with ACE inhibitor and beta-blocker 2
• While her EF is 38%, the symptomatic deterioration and elevated natriuretic peptides justify MRA initiation 2
• Critical caution: Her potassium is already 5.4 mmol/L and creatinine 160 µmol/L—start with 12.5 mg daily and check electrolytes and renal function in 1 week 2
• MRAs reduce mortality and heart failure hospitalization 2
• Hold if potassium >5.5 mmol/L or creatinine increases significantly 2

2. SGLT2 Inhibitor

• Add Dapagliflozin 10 mg PO daily or Empagliflozin 10 mg PO daily 4
• SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality irrespective of diabetes status 4
• These agents reduce heart failure hospitalization and improve quality of life 4
• Can be initiated even during mild volume overload 4
• Monitor for volume depletion, urinary tract infections, and genital mycotic infections 4

3. Consider ARNI (Angiotensin Receptor-Neprilysin Inhibitor)

• Replace Enalapril with Sacubitril/Valsartan 24/26 mg PO BID, titrate to 97/103 mg BID 2
• The 2016 ESC guidelines recommend ARNI in place of ACE inhibitor for patients with HFrEF who remain symptomatic despite optimal medical therapy 2
• ARNI reduces cardiovascular death and heart failure hospitalization more effectively than ACE inhibitors alone 2
• Timing: Wait 36 hours after last ACE inhibitor dose before initiating ARNI to avoid angioedema 2
• Given her elevated natriuretic peptides and symptomatic status, ARNI is strongly indicated 2

Current Medication Optimization

Beta-Blocker Titration

• Increase Metoprolol from 25 mg daily to target dose 2
• Target dose for metoprolol succinate is 200 mg daily 2
• Uptitrate gradually (double dose every 2 weeks) as tolerated by heart rate and blood pressure 2
• Beta-blockers reduce mortality and hospitalization in HFrEF 2

ACE Inhibitor Optimization (if not switching to ARNI)

• Current Enalapril 10 mg BID is appropriate, but could be increased to 20 mg BID if tolerated 2
• However, switching to ARNI is preferred given symptomatic status 2

Medication Sequencing Strategy

1. Immediate: Discontinue Naproxen, start Furosemide 40 mg daily 1, 2
2. Week 1: Add SGLT2 inhibitor (Dapagliflozin 10 mg daily) 4
3. Week 2: Check electrolytes and renal function; if K+ <5.0 mmol/L, add Spironolactone 12.5 mg daily 2
4. Week 4: Recheck labs; if stable, increase Spironolactone to 25 mg daily and begin Metoprolol uptitration 2
5. Week 6-8: Once stable on ACE inhibitor, beta-blocker, MRA, and SGLT2i, consider switching Enalapril to Sacubitril/Valsartan 2

Monitoring Requirements

• Electrolytes and renal function: Check at baseline, 1 week, 2 weeks, then monthly for 3 months, then every 3-6 months 2
• Blood pressure and heart rate: Check at each visit during uptitration 2
• Weight: Daily patient self-monitoring 2
• Repeat echocardiogram: In 3-6 months after medical optimization to reassess EF and guide device therapy decisions 2

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Heart Failure Medication Chart

Angiotensin-Converting Enzyme Inhibitor (ACEI)

Indication: All patients with HFrEF (LVEF ≤40%) unless contraindicated or not tolerated 2

Impact on HF:

• Reduces all-cause mortality by 23% 2
• Reduces cardiovascular mortality 2
• Reduces heart failure hospitalization 2
• Improves symptoms and functional capacity 2
• Prevents adverse cardiac remodeling and left ventricular dilatation 2

Angiotensin II Receptor Blocker (ARB)

Indication: Alternative to ACEI in patients who cannot tolerate ACEI due to cough or angioedema; not for routine combination with ACEI 2

Impact on HF:

• Reduces cardiovascular mortality (similar to ACEI) 2
• Reduces heart failure hospitalization 2
• Improves symptoms and functional capacity 2
• Better tolerated than ACEI (lower incidence of cough and angioedema) 2

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

Indication: Replacement for ACEI/ARB in ambulatory patients with HFrEF who remain symptomatic despite optimal medical therapy with ACEI, beta-blocker, and MRA; requires elevated natriuretic peptides (BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL, or if HF hospitalization within 12 months: BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL) 2

Impact on HF:

• Reduces cardiovascular death by 20% compared to ACEI 2
• Reduces heart failure hospitalization by 21% compared to ACEI 2
• Reduces all-cause mortality 2
• Improves quality of life and functional capacity 2
• Superior to ACEI alone for reducing sudden cardiac death 2

Mineralocorticoid Receptor Antagonists (MRA)

Indication: All symptomatic patients (NYHA Class II-IV) with HFrEF and LVEF ≤35% despite treatment with ACEI and beta-blocker; requires K+ ≤5.0 mmol/L and eGFR >30 mL/min/1.73m² 2

Impact on HF:

• Reduces all-cause mortality by 30% 2
• Reduces cardiovascular mortality 2
• Reduces heart failure hospitalization by 35% 2
• Reduces sudden cardiac death 2
• Improves symptoms and functional capacity 2

Beta-Blockers

Indication: All patients with stable HFrEF (LVEF ≤40%) unless contraindicated; one of three evidence-based beta-blockers: bisoprolol, carvedilol, or metoprolol succinate 2

Impact on HF:

• Reduces all-cause mortality by 34% 2
• Reduces cardiovascular mortality 2
• Reduces sudden cardiac death 2
• Reduces heart failure hospitalization 2
• Improves left ventricular ejection fraction and reverses adverse remodeling 2
• Improves symptoms and functional capacity 2

SGLT2 Inhibitors

Indication: All patients with HFrEF (LVEF ≤40%) regardless of diabetes status; dapagliflozin or empagliflozin 4

Impact on HF:

• Reduces cardiovascular death by 14% 4
• Reduces all-cause mortality 4
• Reduces heart failure hospitalization by 30% 4
• Improves quality of life (Kansas City Cardiomyopathy Questionnaire scores) 4
• Reduces worsening renal function and serious adverse renal events 4
• Benefits independent of diabetes status, baseline natriuretic peptides, or ejection fraction 4

Digoxin

Indication: Symptomatic patients with HFrEF in sinus rhythm who remain symptomatic despite optimal medical therapy; also for rate control in atrial fibrillation 2

Impact on HF:

• Reduces heart failure hospitalization 2
• Improves symptoms and functional capacity 2
• No effect on mortality 2
• Narrow therapeutic window requires monitoring of digoxin levels and renal function 2

Loop Diuretics (e.g., Furosemide)

Indication: All patients with signs or symptoms of congestion (volume overload) to achieve and maintain euvolemia 2

Impact on HF:

• Reduces symptoms of congestion (dyspnea, edema) 2
• Improves exercise capacity 2
• Reduces heart failure hospitalization 2
• No proven effect on mortality (not studied in large RCTs) 2
• Should be used at lowest dose necessary to maintain euvolemia 2
• Patients can be trained to self-adjust diuretic dose based on daily weights 2

Vasodilators (Hydralazine-Isosorbide Dinitrate, H-ISDN)

Indication: Self-identified African American patients with NYHA Class III-IV HFrEF despite optimal medical therapy; alternative in patients who cannot tolerate ACEI, ARB, or ARNI 2

Impact on HF:

• Reduces all-cause mortality by 43% in African American patients 2
• Reduces heart failure hospitalization 2
• Improves quality of life 2
• Improves functional capacity 2
• Less effective than ACEI/ARB/ARNI in non-African American populations 2