Pacing Induced Cardiomyopathy

Pacing induced cardiomyopathy (PICM) is a new fall in left ventricular ejection fraction, usually by 10 points or more to under 50%, attributable to a high burden of right ventricular pacing, after other causes have been excluded.

It develops in about 10 to 20% of patients with a ventricular pacing burden of 20% or more (range 6 to 25%, depending on definition). Onset is months to years after implantation, commonly within the first 3 to 4 years.

Risk factors are a right ventricular pacing burden over 20% to 40%, baseline ejection fraction under 55%, a paced QRS duration over 150 ms, male sex, atrial fibrillation, previous myocardial infarction, chronic kidney disease and longer duration of pacing.

Right ventricular apical pacing carries more risk than septal or conduction system pacing. Heart failure hospitalisation, atrial fibrillation and mortality rise in affected patients.

Pathophysiology. Pacing from the right ventricle produces a left bundle branch block pattern of activation. Late lateral wall activation causes septal flash, dyssynchrony, reduced stroke volume, functional mitral regurgitation and eccentric hypertrophy, with adverse remodelling and neurohumoral activation.

The process is largely reversible with restoration of synchronous activation.

• New or worsening exertional dyspnoea, fatigue, orthopnoea, oedema and reduced exercise capacity, months to years after implantation.
• New atrial fibrillation, ventricular arrhythmia, or increased shocks from a defibrillator.
• Signs of heart failure: third heart sound, displaced apex, functional mitral regurgitation murmur, raised venous pressure.
• Wide-QRS paced ECG with left bundle branch block morphology (a paced QRS over 150 ms predicts risk).

Red flags.

• Falling ejection fraction in a patient with over 20% ventricular pacing
• Heart failure admission
• New atrial fibrillation
• Ventricular arrhythmia or syncope
• Dependence on pacing with a paced QRS over 150 ms

• Device interrogation. Percentage of ventricular pacing (cumulative and recent), paced QRS morphology and duration, AV conduction, atrial and ventricular arrhythmia burden, lead thresholds, sensing and impedance.
• Echocardiography. Compare with the baseline study at implantation. Ejection fraction, septal flash, apical rocking, mitral regurgitation, dyssynchrony, right ventricular and atrial size.
• ECG for paced QRS duration. Cardiac MRI for scar and other cardiomyopathy.
• Exclusion of other causes. Ischaemia (stress imaging, CT or angiography), tachycardia (ambulatory ECG), thyroid function, alcohol, anaemia, valve disease, natriuretic peptide.
• Diagnosis is made when the fall in ejection fraction occurs with a high pacing burden and no other cause is found.

Differential diagnosis.

• Progression of underlying cardiomyopathy or ischaemic heart disease
• Tachycardia induced cardiomyopathy and atrial fibrillation with rapid rates
• Lead related tricuspid regurgitation or perforation
• Pacemaker syndrome
• Myocarditis and infiltrative cardiomyopathy
• Valve disease and hypertensive heart disease
• Alcohol and thyroid disease
• Loss of capture and lead failure

• Upgrade to resynchronisation. Replace right ventricular pacing with biventricular pacing, or with conduction system pacing (left bundle branch area or His bundle pacing). Indicated when ejection fraction is under 50% with a pacing burden of 20% to 40% or more and heart failure symptoms or falling ejection fraction. About 70 to 90% of patients improve ejection fraction by 10 points or more, and many normalise it. Conduction system pacing is an alternative when coronary sinus lead placement fails. Use a defibrillator capable device when primary prevention criteria for ejection fraction are met (35% or less after at least 3 months of optimal therapy).
• Reduce unneeded ventricular pacing in the interim: programme AV search hysteresis or algorithms that favour intrinsic conduction, and use atrial pacing in sinus node dysfunction with intact AV conduction.
• Heart failure drug therapy.
  • Sacubitril/valsartan 49/51 mg orally twice daily, doubled at 2 to 4 weeks to the target 97/103 mg twice daily (maximum 194/206 mg daily). Start 24/26 mg twice daily if not on an ACE inhibitor or angiotensin receptor blocker, on low doses, with eGFR under 30 mL/min/1.73 m2, or with moderate liver impairment. Stop any ACE inhibitor 36 hours before. Contraindicated with previous angio oedema, severe liver impairment and pregnancy. Check potassium and creatinine 1 to 2 weeks after each change.
  • Bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to the target 10 mg once daily, maximum 10 mg daily in heart failure. Contraindicated in cardiogenic shock, high grade AV block without a pacemaker (acceptable when a pacemaker is present), sick sinus syndrome without pacing and severe asthma.
  • Spironolactone 25 mg orally once daily (12.5 mg at eGFR 30 to 49 mL/min/1.73 m2), up to 50 mg daily. Check potassium and creatinine at 1 week and 4 weeks, then every 3 months. Withhold at potassium over 5.5 mmol/L and avoid at eGFR under 30 mL/min/1.73 m2.
  • Dapagliflozin 10 mg orally once daily, long term. Start at eGFR 25 mL/min/1.73 m2 or more. Withhold during acute illness with poor oral intake. Contraindicated in type 1 diabetes.
  • Furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care). Monitor sodium, potassium and creatinine.
• Atrial fibrillation: apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term.
• Prevention at first implantation. Choose biventricular or conduction system pacing when AV block is present, ejection fraction is 50% or less, and a ventricular pacing burden over 40% is expected. Avoid apical lead positions.
• Upgrade risks. Pocket infection and lead complications (about 3 to 4%), venous occlusion, tricuspid valve injury, and coronary sinus dissection. Give antibiotic prophylaxis (cefazolin 2 g intravenously as a single dose 30 to 60 minutes before incision, 3 g if over 120 kg) and use an antibacterial envelope in high risk upgrades. Check venous anatomy first.

Special groups. Pacemaker dependent older adults with mild dysfunction may be managed with drug therapy and close follow up. Younger or active patients need an upgrade.

Monitoring. Echocardiography at 3 and 6 months after upgrade, then yearly. Device check at 2 to 12 weeks, then every 3 to 12 months with remote monitoring, aiming for biventricular pacing over 98%. Natriuretic peptide with symptoms. Potassium and creatinine 1 to 2 weeks after each change of sacubitril/valsartan and at 1 week and 4 weeks after starting spironolactone.

Referral and escalation. Refer to the device clinic or electrophysiology. Urgent for heart failure admission, ventricular arrhythmia, loss of capture in a dependent patient, or suspected lead problem.