Case Studies in Advanced Monitoring: OptiVol W. H. Wilson Tang, MD Assistant Professor in Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Assistant Program Director General Clinical Research Center (GCRC) Section of Heart Failure & Cardiac Transplantation Medicine Cleveland, Ohio

M.L.H.: Medical History 67-year-old female Long history of dilated (nonischemic) cardiomyopathy with mitral regurgitation with mild symptoms Outside echo: EF 20%, 3+ mitral regurgitation Epicardial lead placement of biventricular pacer/ICD in February 2005, with subsequent monthly admissions AV nodal ablation in April 2005 for poorly controlled atrial fibrillation Referred for evaluation for transplantation versus advanced surgical therapies EF, ejection fraction; ICD, implantable cardioverter defibrillator; AV, atrioventricular.

June 2005: Medications Amiodarone 200 mg daily Digoxin 0.125 mg daily UroMag 140 mg daily Warfarin 2.5 mg daily Aspirin 81 mg daily Captopril 25 mg three times daily Metoprolol succinate 25 mg daily Furosemide 80 mg daily Potassium 20 mEq daily

June 2005: Initial Clinic Visit Appeared lethargic, mild respiratory distress ACC Stage C-D, NYHA III Weight 207 lbs, height 5’ 6’’ BP 98/65 mm Hg, pulse 88 (irregular) JVP 8-10 cm Prominent S3, with 2/6 systolic murmur at apex Decreased pedal pulses, cool extremities but no significant edema Sluggish due to dyspnea, but nonfocal neurological signs Admitted for hemodynamically tailored therapy, requiring transient dobutamine and furosemide IV Discharged on home dobutamine infusion ACC, American College of Cardiology; NYHA, New York Heart Association; BP, blood pressure; JVP, jugular venous pressure.

July 2005: Hospitalization Re-admitted for congestive heart failure Hemodynamically tailored therapy with switch to IV milrinone infusion Coronary sinus lead revision with InSync Sentry implantation Slow titration of metoprolol succinate in attempt to control rapid atrial fibrillation Stable on furosemide 40 mg daily and home milrinone infusion at discharge

September 2005: Clinic Visit Follow-up: Returns to clinic with no improvement in physical activity and dyspnea BP 88/50 mm Hg, pulse 76 (irregular), weight 209 lbs JVD 9 cm, prominent S3, 2/6 systolic murmur (unchanged) Scanty rales at right base 1+ pedal edema, warm extremities Laboratory evaluation: Sodium 135 mmol/L BUN 22 mg/dL Creatinine 0.9 mg/dL BNP 1,968 pg/mL

September 2005: Cardiac Compass with OptiVol OptiVol fluid index AT/AF total hours/day 24 Plan: Increased furosemide to 40 mg twice daily Added spironolactone 25 mg daily Continue milrinone infusion Close monitoring of congestive symptoms >200 20 16 12 160 8 4 120 V. Rate during AT/AF (bpm) Max/day Avg/day >200 150 80 100 <50 40 Patient activity hours/day 4 3 2 Fluid 1 Aug 05 Oct 05 Avg V. rate (bpm) Day Night >120 Thoracic Impedance (ohms) 100 >100 80 Daily Reference 60 <40 90 Heart rate variability (ms) >200 160 80 100 80 70 <40 % Pacing/day Atrial Ventricular 100 60 75 50 50 25 Aug 05 Oct 05 Aug 05 Oct 05

October 2005: Follow-up Clinic Visit Follow-up with good diuresis and 18-lb weight loss Improved symptoms and activity level No JVD, regular rate and rhythm, no edema Laboratory: BNP reduced to 1,213 mg/dL from 1,968 mg/dL Sodium improved to 138 mmol/L Stable creatinine at 0.8 mg/dL Furosemide dose reduced to 40 mg daily, metoprolol succinate at 50 mg daily

February 2006: Follow-up Clinic Visit Noticed 3-lb weight gain BP 120/65 mm Hg, pulse 75 (regular) Symptoms overall unchanged Mild JVD, cardiac examination unchanged, no edema Laboratory evaluation: Sodium 141 mmol/L Creatinine 0.9 mg/dL BNP 794 pg/mL

February 2006: Cardiac Compass with OptiVol OptiVol fluid index AT/AF total hours/day 24 20 >200 16 12 8 160 4 V. Rate during AT/AF (bpm) Max/day Avg/day >200 120 150 100 80 <50 40 Patient activity hours/day 4 3 2 Fluid 1 Aug 05 Oct 05 Dec 05 Feb 06 Avg V. rate (bpm) Day Night >120 Thoracic Impedance (ohms) 100 >100 80 Daily Reference 60 <40 90 Heart rate variability (ms) >200 160 80 100 80 70 <40 % Pacing/day Atrial Ventricular 100 60 75 50 50 25 Aug 05 Oct 05 Dec 05 Feb 06 40 Aug 05 Oct 05 Dec 05 Feb 06 AT/AF, atrial tachycardia/atrial fibrillation; V. rate, ventricular rate.

February 2006: Follow-up Clinic Visit Increased furosemide to 40 mg twice daily for 4 days then resumed 40 mg once daily Prompt resolution of congestion and OptiVol index Repeat BNP 336 pg/mL NYHA II-III with slow weaning of milrinone infusion

March 2006: Cardiac Compass with OptiVol OptiVol fluid index Got a call from home nurse regarding recent 8-lb weight gain later, asked to readjust milrinone dose Phone contact revealed no significant signs and symptoms of edema. No change in OptiVol index Further inquiry revealed increase night-time snacking and food intake >200 160 120 80 40 Fluid Aug 05 Oct 05 Dec 05 Feb 06 Thoracic Impedance (ohms) >100 Daily Reference 90 80 70 60 50 40 Aug 05 Oct 05 Dec 05 Feb 06

Take-Home Points OptiVol fluid index tracks with clinical status in the setting of congestion: Clinical signs and symptoms of congestion Plasma BNP levels Fluid weight (but not fat) Precedes development of overt symptoms Tracks responses to therapy Need to evaluate other parameters (activity, rhythm, heart rate variability) and clinical status in parallel with OptiVol index