Iatrogenic Heart Disease aegrescit medendo (the remedy is worse than the disease)

1. Iatrogenic Heart Diseaseaegrescit medendo (the remedy is worse than the disease) Gregory L. Sheehy, M.D. Primary Care Conference May 10, 2006

2. I. Iatrogenic…a definition Induced in a patient by a physician’s words or actions The American Heritage Dictionary, 2nd Ed.

3. OR • An iatrogenic disorder occurs when the deleterious effects of a therapeutic or diagnostic regimen cause pathology… • However, the harm that a physician can do is not limited to the imprudent use of medications or procedures. Equally important are ill-considered or unjustified remarks. Harrison’s Principles of Internal Medicine, 14th ed., p. 4

4. II. Case ReportFirst visit 01/02/1998 (transferring from another clinic) • 63 year old woman who feels well but is recovering from a recent traumatic L1 compression fracture • Other problems: • Hypertension-145/75-Atenolol 50mg/Amlodipine 5mg • Hypertriglyceridemia-Gemfibrozil 300 mg bid • Asymptomatic diverticulosis • Asymptomatic mitral valve prolapse-no murmur noted-? Click • Vaginal hysterectomy and cholecystectomy, remote • Treatment plan: • Medications renewed • Scheduled for complete exam in April of 1998 • Patient leaving for Arizona for the remainder of the winter

5. Case Report, cont.Flash forward to CPE 11/11/05, patient now 71 years • Problem list • Hypertension-110/70-Atenolol 50 mg/Amlodipine 5mg • Occasional mild exertional chest pain • Cold/numb feet-improved with brief trial off atenolol • Hypertriglyceridemia-Gemfibrozil 600 mg bid • Recurrent UTIs with significant episode of pyelonephritis in July 2004 • Recurrent episodes of diverticulitis (3 in all) with colonoscopy in 2003, unremarkable except for tics • S/p acute appendicitis with perforation/peritonitis in June 2002 • H/o mitral valve prolapse with echocardiogram in May, 1999, showing no MVP/regurgitation • S/p vaginal hyst and cholecystectomy, remote • At this visit, her most significant complaint is that “the cold feet and somewhat numb sensation in her feet” is something that she is finding pretty intolerable “The incidence of cold extremities during atenolol treatment was 58% in one study”, Feleke et al, 1983, Micromedex

6. Case Report, cont. • Treatment plan • Taper off Atenolol • Discontinue Amlodipine • Gradual start of Lisinopril 20mg/HCTZ 12.5 mg • Recheck in 2 weeks

7. Case Report, cont.Return visit approximately 10 days later, 11/22/05, on Lisinopril and HCTZ • Problem list • Hypertension-100/60 in both arms • Chest pain, not severe, but clearly worse • Faster HR/palpitations/DOE-no PND • New cardiac murmur-quite loud-IV/VI pansystolic murmur with thrill all over precordium and around to her back and very active precordium • Studies • EKG: LVH with poor R wave progression, no acute ischemic changes • Chest xray: normal • Enzymes/lytes: normal except for creatinine of 1.5, a rise • Plan • Patient did not look acutely ill but was obviously uncomfortable • Admit for evaluation and treatment • Metoprolol 50 mg given immediately—within one hour, she started to feel better • Endocarditis/ruptured valve leaflet/aortic dissection under consideration

8. III. Major Learning Objective…Look at all of the data!

9. My bias failed me:“You see only what you look for and recognize what you know”

10. Echocardiogram, 5/28/99 “No significant valvular disease, specifically, there is no mitral valve prolapse or regurgitation. Asymmetric septal hypertrophy with no systolic anterior motion of the mitral valve. Left ventricular size is normal and systolic function is hyperdynamic with an estimated ejection fraction of 75%. There is evidence for delayed left ventricular relaxation.”

11. Echocardiogram, 11/23/05 “Overall systolic function is hyperdynamic. Moderate systolic anterior motion of the mitral valve is noted. There is dynamic left ventricular outflow tract obstruction at rest, with a peak velocity of 3.5m/sec, and a peak gradient of 49 mmHg. Moderate valvular regurgitation of the mitral valve.”

12. What happened?...I had unmasked Hypertrophic Cardiomyopathy

13. Why? • Stopped beta blocker- increased heart rate • Started ACE inhibitor with a diuretic- decreased preload and afterload

14. Follow up Patient now on Verapamil 240 mg SR twice daily and feels well

15. IV. Hypertrophic Cardiomyopathy (HCM) • It is an autosomal dominant genetic disease • All first degree relatives should get tested yearly ages 12 to 18 and every 5 years from age 18 to ? (delayed onset of hypertrophy is an issue) • Echocardiogram is the screening test of choice • Most electrocardiograms are abnormal with LVH and often ST-T wave changes • A “normal” ECG in HCM is unusual

16. HCM, cont. • Prevalence of HCM is somewhere between 1:350 to 1:650 individuals • Many patients with HCM have no symptoms and therefore many cases are found by screening. • The issue is that a significant portion (25-40%) will eventually develop symptoms • Most common symptom is dyspnea with exertion (DOE) • Other symptoms include chest pain, presyncope/syncope, and palpitations • Women tend to have more symptoms with advancing age • This is possibly due to smaller LV cavity size

17. HCM, cont. • Worse prognosis • Early age at onset (i.e. < 20 years of age) • Severity of symptoms at time of diagnosis • Variable other clinical markers • Outflow gradient > 30 mmHg • LV wall thickness >25 mm • Atrial fibrillation • Mortality rates of men=women • The “usual” stated annual mortality rate of 3-5% is too high…probably closer to 1%

18. Key Exam Findings • A murmur that increases from a change from sitting or squatting to the upright position • A murmur that decreases going from a standing to sitting, squatting, or lying position

19. Treatment • Medications • Beta blockers • Verapamil • Disopyramide • Other • Surgical resection • Chemical ablation • Defibrillator • Heart transplant

20. References • Up to Date 2006, “Hypertrophic Cardiomyopathy” • Maron BJ, Casey SA, Poliac LC, et al. Clinical course of hypertrophic cardiomyopathy in a regional United States cohort. JAMA 1999; 281: 650-655. • Olivetto I, Maron MS, Adabog AS, et al. Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy. J Am Coll Cardiol 2005; 46: 480-7.