NYU Medical Grand Rounds Clinical Vignette

1. NYU Medical Grand Rounds Clinical Vignette Rachel Bond, MD Class of 2012 Tuesday, April 10, 2012 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

3. Chief Complaint • 67 year-old woman with three weeks of progressive shortness of breath and lower extremity edema. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

4. History of Present Illness • The patient was in her usual state of health until the late 1990s when she developed progressive shoulder weakness, leading ultimately to evaluation by a neurologist who diagnosed her with limb-girdle muscular dystrophy with LMNA (lamin A/C) gene mutations. • From the time of diagnosis, the patient received supportive care as treatment. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

5. History of Present Illness • She subsequently developed progressive shortness of breath. • An extensive evaluation led to the diagnosis of severe restrictive lung disease, obstructive sleep apnea and severe pulmonary hypertension, treated with nocturnal CPAP, sildenfail and bosentan. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

6. History of Present Illness • Several weeks prior to her presentation, her sildenafil was transitioned to tadalafil, and bosentan was continued. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

7. History of Present Illness • She subsequently developed reduction of exercise tolerance from 3 blocks to one block with new lower extremity edema. • Her two-pillow orthopnea remained stable, and she denied chest pain or palpitations. • For her worsening pulmonary symptoms and exercise intolerance, she presented to the emergency room UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

8. Additional History • Past Medical History: • Limb-girdle muscular dystrophy with lamin A/C mutations • Restrictive lung disease • Obstructive sleep apnea • Asthma • Severe pulmonary hypertension • Paroxysmal atrial fibrillation • Diastolic heart failure • Stroke • Past Surgical History: • none • Social History: • Denies tobacco, drug, alcohol abuse • Family History: • Mother with muscular dystrophy. • Multiple family members with early/sudden cardiac death. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

9. Additional History • Allergies: • No Known Drug Allergies • Medications: • tadalafil 20mg po daily • furosemide 40mg po daily • simvastatin 40mg po at bedtime • warfarin 2mg po at bedtime • budesonide soln bid • fluticasone/salmeterol 500mcg/50mcg bid • albuterol/atrovent nebs prn UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

10. Physical Examination • Well-appearing in no acute distress • Vitals: T:98.6F, BP:120/85, HR:57 RR:16, and SaO2: 86% on RA and 96% on 2LNC • JVD to 14cm with hepatojugular reflex • Decreased breath sounds bilaterally/diffuse rales • Irregularly irregular HR with prominent P2 • 1+ bilateral lower extremity edema to knees • Gross atrophy of shoulder girdle muscles, 3/5 strength of proximal muscles of upper limbs bilaterally, but 4/5 in both lower limbs. Power preserved in distal muscles with deep tendon reflexes diminished in lower limbs and absent in upper limbs (baseline) UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

11. Laboratory Findings • CBC: • WBC 8,200, Hg 14.5g/dL, Platelets 159,000 • Basic Metabolic panel: • Na 144 meq/L • K 4.1 meq/L • Cl 103 meq/L • Bicarb 35 meq/L • BUN19 mg/dL • Creatinine 0.4 mg/dL UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

12. Laboratory Findings • Brain Natriuretic Peptide 1170 pg/mL • Troponin 0.027 mg/dL • Arterial Blood Gas on 2L nasal cannula • pH: 7.31 • pCO2: 72mmHg • pO2: 132mmHg • Bicarb: 35meq/L • SaO2: 99% • Lactic Acid: 0.7mg/dL • INR 2.7 • Hepatic panel within normal limits UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

13. Other Studies • ECG: • normal sinus rhythm with premature ventricular complexes, isolated Q-wave in I, and incomplete right bundle branch block • Chest X-ray • Poor inspiratory effort with patchy bilateral opacities consistent with pulmonary edema UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

14. Other Studies • Transthoracic Echocardiogram • LV ejection fraction 65% • Impaired diastolic filling • Severe biatrial dilitation • Severe pulmonary hypertension • Estimate PA systolic pressure 67mmHg UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

15. Working Diagnosis • Multifactorial congestive heart failure exacerbation complicated by hypercapneic respiratory failure • LV diastolic dysfunction • Severe pulmonary hypertension • Recent medication changes • Musculodystrophy/restrictive lung disease • Obstructive sleep apnea UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

16. Hospital Course • The patient was admitted to the step-down unit for close monitoring and was treated with intravenous diuretics and her taldenafil was discontinued. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

17. Hospital Course • Her course was complicated by episodes of intermittent tachycardia and bradycardia with multiple >3second pauses on telemetry. • Given arrhythmia and family history of sudden cardiac death, a dual chamber ICD/pacemaker was implanted. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

18. Hospital Course • The patient was successfully diuresed and her heart failure symptoms improved to baseline. • She was discharged home with outpatient follow-up with cardiology. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

19. Final Diagnosis • Multi-factorial congestive heart failure exacerbation with presumed tachy-brady syndrome and cardiomyopathy due to lamin a/c mutation. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

20. Arthur C. Fox Visiting Professorship in Cardiovascular Biology Arthur C. Fox, MD Christine Seidman, MD Previous Recipients: 2002 - Peter Libby, MD 2003 - Kenneth Chien, MD, PhD 2004 - Eugene Braunwald, MD • 2005 - Wilson Colucci, MD • 2006 - Eric Olson, PhD 2007 - Itzhak Kronzon, MD 2008 - Leslie Leinwand, PhD 2009 - Aldons J. Lusis, PhD 2010 – Joseph Loscalzo, MD, PhD 2011 – Daniel Rader, MD