Autopsy Conference03/02/2016

Khushboo Gandhi, MD PGY 1, St Luke’s Hospital IM residency program

History of Present Illness:79-year-old WM presents with chest pain and SOB on exertion. Ten days ago - chest pain, tightness on anterior chest, with palpitation, resolved with sublingual nitroglycerin. Past three to four days - chest pain continued despite NTG now radiating to left arm. Shortness of breath on exertion and feeling tired easily. Ten days ago - took Pseudoephedrine for allergy. He went to Salem Township hospital, Troponins mildly elevated 0.15, BNP 180. Received NTG sublig, Lasix 80 mg, Nitro-patch and heparin bolus, transferred to St Luke's' telemetry as his cardiologist was here.

Past Medical and Surgical history:CAD s/p CABG x 5 in 1982, attempt at a PCI in 2008 with balloon angioplasty, MI in 2011Recent cardiac catheterization in December 2014 - total occlusion of the native circulation and patent but severely diseased 2 out of 3 venous graftsInfrarenal AAA 5.4 X 4 cm, follows vascular surgeon, USG every 6 monthsTransient ischemic attack in 12/2014left subclavian arterial aneurysm and an aberrant right subclavian artery s/p bilateral carotid-subclavian bypass and TEVAR with stent placement and embolization of the bypassed segments of the bilateral subclavian arteries in January 2015.Hypertension HyperlipidemiaChronic Kidney Disease

OSA on CPAP during night History of gastric ulcersOsteoarthritisHernia repair

Family History:heart disease and hypertension in father

Social Hx:Tobacco Use - Quit in 2008Alcohol Use - occasional beer per week or 2 weeks.Recreational Drug Use - Never drug user

Home meds:Crestor 40 mg, Metoprolol Succinate ER 25 mg, Nitrostat 0.4 mg sublingual, Norco 5 mg-325 mg, Plavix 75 mg, Viagra 100 mg, amLODIPine 5 mg, aspirin 81 mg, cloNIDine 0.1 mg, fluticasone nasal spray, furosemide 20 mg as needed, omeprazole 20 mg.

Physical Exam: VITAL SIGNS: Temperature 36.6, heart rate 80, respiratory rate 18, O2 saturation 96% on room air, blood pressure 137/89. Height 177 cm, weight 97.2, body mass index 31.03. CONSTITUTIONAL: No fever or chills.GENERAL APPEARANCE: Looks appropriate for his age. Well-built, well-nourished appearance. HEAD: Normocephalic, atraumatic.MOUTH AND NOSE: Normal mucosa.EYES: Anicteric sclerae. Normal conjunctivae. Pupils equal, round, and reactive to light and accommodation. No sinus tenderness with palpation. Normal ears and hearing. NECK: Supple. No visible jugular venous distention. No palpable mass or thyromegaly. No carotid bruits heard. HEART: Irregularly irregular. Unable to appreciate any audible murmur, gallop, or rub. LUNGS: Clear to auscultation bilaterally without any added sounds currently. CHEST WALL: No tenderness with palpation. ABDOMEN: Positive bowel sounds. Soft and nontender.EXTREMITIES: Very trace edema bilaterally. Palpable weak pedal pulses. No calf tenderness. No tremors. BACK: No spine tenderness. No costovertebral tenderness.

Labs:

Troponins: 0.15 → 0.82 → 1.70 → 1.58

EKG: Atrial fibrillation, Rightward axis, Nonspecific ST abnormality Compared to prior on 11-Dec-2014: ST abnormality is new

CHEST 2 VIEWS 11/11/2015 - unremarkableSmall left pleural effusion or pleural scar, Postoperative changes. No definite infiltrate.

Assessment and plan:Symptomatic new onset of atrial fibrillation with moderate ventricular response heart rate around 90s, likely secondary to recent

OTC medication, pseudoephedrine and Claritin-D. Before transfer, he received 25 mg of metoprolol and heparin bolus. Seen by cardiologist, and on subcutaneous Lovenox, metoprolol

Elevated troponin - non-ST elevated myocardial infarctionHistory of coronary artery disease - known complex coronary anatomy with bypass surgery more than 30 years ago and attempt at

a percutaneous intervention in 2008, stents could not be deployed, but he did have balloon angioplasty. On aspirin, Plavix, statin, metoprolol, nitroglycerin patch.

Cardiac catheterization in December 2014 - showed total occlusion of the native circulation and patent but diseased grafts to marginals, patent graft to the LAD, and a patent graft to the right coronary artery with disease in the posterior descending distal to it.

History of abdominal aortic aneurysm, 5.2x4 cm in size, follows vascular surgeon, usg q 6 monthsDyslipidemia, on statin.Chronic diastolic congestive heart failure on small dose of furosemide. chronic kidney disease stage II. Hypertension on Imdur and metoprolol, amlodipineHistory of recent transient ischemic attack in 12/2014, on aspirin, Plavix, and statin. History of right subclavian bypass surgery January 12, 2015, and Left carotid subclavian artery bypass, thoracic aortic stent graft

placement, bilateral subclavian artery embolization 01/19/2015. History of gastric ulcers status post upper endoscopy, colonoscopy in September 2011 for melena, on omeprazole.Ex-tobacco use, quit in 2008, No COPD.

Day 2 11/12/2015Patient still in A. fib with moderate ventricular response, HR 80s/minAngina, currently controlledElevated troponin trending down (1.70 → 1.58 → 0.82)Repeat EKG - No Significant Changes compared t0 11/11/2015Decided against cardiac cath - as troponin trending down and according to patient wish. if symptoms persist, he would need cardiac cath and possible CABG redo Dyspnea, resolved. Decided against CT chest or USG of lower ext for suspected PE, as pt already received 2-3 dose of Lovenox, and in the absence of calf pain, lovenox discontinued later that day.

Echo 11/12/20151.The rhythm during the study was atrial fibrillation.2.Mild to moderate concentric left ventricular hypertrophy.3.Normal left ventricular diastolic function for age as measured by tissue Doppler/Mitral Doppler indices.4.Normal left ventricular cavity size and systolic function. The left ventricular ejection fraction is measured at 54%.5.There is mild left atrial enlargement.6.Mild focal thickening of the anterior mitral valve leaflet.7.Mild mitral regurgitation.8.Tricuspid aortic valve. Trace aortic regurgitation. No significant aortic stenosis.9.Tricuspid regurgitant jet velocity envelope is inadequate for determination of RVSP.10.Compared to prior study of 12/12/2014, there is no significant change.

Day 3 11/13/2015Pt felt “great”Labs unremarkableDischarged homeDISCHARGE MEDICATIONS:1. Acetaminophen/hydrocodone 5 mg/325 mg 1 tablet oral every 4 hours p.r.n. for pain. 2. Loratadine 10 mg oral daily.3. Amlodipine 5 mg oral daily.4. Eliquis 5 mg oral b.i.d. for 30 days.5. Clonidine 0.1 mg oral p.r.n. for high blood pressure.6. Plavix 75 mg oral daily.7. Fluticasone, 1 spray nasal b.i.d.8. Furosemide 20 mg oral as needed.9. Imdur 30 mg oral daily.10. Metoprolol 25 mg oral daily.11. Nitroglycerin 0.4 sublingual as needed p.r.n. for chest pain.12. Omeprazole 20 mg oral daily.13. Crestor 40 mg orally at bedtime.

Day 4 11/14/2015Pt presented to ER with worsening chest discomfort associated with some nausea and minimal diaphoresis.

Physical examination:Elderly white male, currently in no acute distress, alert, oriented, and cooperative. Vitals: afebrile. Pulse 96, atrial fibrillation, respirations 18, blood pressure 120/90. Neck is supple without jugular venous distention. Lungs are clear. Heart is irregularly irregular. There is a grade 2/6 systolic ejection murmur. No diastolic murmur and no gallop. Radial, carotid, and femoral pulses are palpable. Pedal pulses are diminished. Abdomen is unremarkable. EXTREMITIES: No significant edema.

EKG: Course Atrial fibrillation, Rightward axis, Nonspecific ST abnormality , probably digitalis effectCompared to prior on 12-Nov-2015: No Significant Changes

CHEST SINGLE VIEW: No acute process or significant change in the chest.

Labs: CBC unremarkable, BUN 22, Creatinine 1.4, Troponin 1.64Serial troponins: 1.64 → 11.80

Plan: Admitted to telemetry, However as chest pain was relieved, plan was made to continue medical management. In case of recurrent angina, consider catheterization. Imdur and metoprolol dose doubled.

Day 5 11/15/2015 Pt asymptomatic, 2 episodes of NSVT (6 beats) during nightTroponin trending down to 1.64 → 11.8 → 8.57 → 3.53A fib. rate controlled, HR in 70s-80s

Same day @ 1716On call resident was called for chest pain, HR 110s/min, BP 160/112Chest pain resolved after two sublingual NTG.Trop stat 3.53Repeat EKG: Atrial fibrillation with rapid ventricular responseRightward axisMarked ST abnormality, possible inferolateral subendocardial injuryCompared to prior on 14-Nov-2015: HR is faster and ST changes are more pronounced

Serial troponins: 3.53 → 3.69 → 2.59

Day 6 11/16/2015Pt was taken for cardiac catheterization Report:1. Normal left ventricular ejection fraction approximately 55% with anterolateral hypokinesia. 2. Moderately elevated LVEDP of 17 mmHg.3. No mitral regurgitation.4. Severe native 3-vessel coronary artery disease.5. Left internal mammary artery to the left anterior descending is patent and visualized by a nonselective ascending aortogram. 6. The saphenous vein graft to the right posterior descending artery is patent with an ostial posterior descending artery stenosis of 80%. 7. The saphenous vein graft to the first diagonal branch of the left anterior descending has a 60% to 70% ostial stenosis. 8. The saphenous vein graft to the second obtuse marginal branch has a 99% ostial stenosis and 60% stenosis at the vein graft anastomosis.

Decision was made to proceed with redo coronary artery bypass grafting. Plavix and eliquis discontinued and Heparin drip was started.

Day 7-9 Transferred to the cardiovascular step down unit and cardiothoracic surgery was consulted for redo sternotomy, redo coronary artery bypass grafting, and possible left atrial appendage excision and pulmonary vein isolation for atrial fibrillation. Surgery was planned on November 20, 2015. Waiting for eliquis, plavix washout and improvement of creatinine. STS risk score was approximately 7.085%.

PFT: Flow volume loop demonstrated moderate reduction of FVC, No airflow obstruction consistent with a restrictive impairment. Recommend lung volume measurement to evaluate this abnormality.

Carotid BL duplex scan1.The right internal carotid artery disease is consistent with a 50-69% stenosis per Doppler, closer to 69% per image.2.The left internal carotid artery disease is consistent with a 50-69% stenosis by Doppler, closer to 69% per image.3.Tandem lesions in the bilateral internal carotid arteries may underestimate the degree of stenosis by Doppler.4.Abnormal flow is noted in the left vertebral artery.5.Patent bilateral common carotid to subclavian artery bypass grafts with PTFE.6.Consider vascular consultation. Consider CTA over MRA if clinically indicated.

Had some chest pain overnight (11/18/2015), started on integrilin drip

Repeat EKG:Atrial fibrillation with rapid ventricular response, Rightward axisMarked ST abnormality, possible inferolateral subendocardial injuryCompared to prior on 15-Nov-2015: No Significant Changes

Serial troponins: 1.77 → 2.30 → 1.81

Day 10, 11/20/2015, Day of surgery

CTS: Redo CABG, Right pulmonary vein isolation, Insertion of an IABP. Details: SVG → marginal of circumflex, SVG → diagonal, SVG → RPD, LIMA found and preservedRight pulmonary vein isolation done, but posterior pericardium very "stuck", so LAA excision and left PVI not done.

Just before sternal closure, he went into VT/VF and could not be cardioverted. Replaced on CPB and successfully converted. Some RV dysfunction was noted after sternotomy. IABP placed for hemodynamic support. Very oozy after second pump run. Blood products replaced: 8u prbc, 5u FFP, 3u SDP, 10u cryo, Factor 7. Sternal closure caused hypotension, so chest left open.

CHEST SINGLE VIEW 11/20/2015 @19:40 Post open heart surgery. Cardiac operative changes with support system as described, Left perihilar infiltrates and possible tiny basal pleural effusion.

Pt was transferred to SICU intubated, with IABP 1:1, on epi, NE, milrinone, DBA, vaso, amiodarone, inhaled flolan. Cardiac index ~2.5 and MAP in 70's on arrival.

Plan: Sedated and intubated.Postoperative Cardiogenic shock, cont IABP 1:1, epinephrine, milrinone, dobutamine. Amiodarone for AF.Inhaled flolan for RV support. Postoperative AKI, cont Foley, monitor UOP, trend Creatinine. Ancef for periop Abx.

Day 11, 11/21/2015, Postop day 1Patient condition relatively unchanged overnight. Slight increase in epi requirement. He remains intubated/sedated, followed commands & moved ext x4, requiring IABP (1:1), epi, levo, vaso, dobutamine, amio, and inhaled flolan for inotropic and pressor support. He continues to make adequate urine, CT w/ 350 cc bloody output overnight, receiving 2nd unit of pRBC for Hgb=7.9.Plan for return to OR later in the week for closure

CHEST SINGLE VIEW 11/21/2015 0600Extensive postoperative changes, as described.Increasing left hemithorax opacification (presumably from hemorrhage or fluid) and right basilar infiltrate or atelectasis.

Renal USG for Acute AKISmall left renal cyst, otherwise normal sonographic exam of the kidneys.

Day 12-13, Postop day 2-3: Develops severe acute kidney injury with anuria, hyperkalemia and acidosisCreatinine: Potassium:

Right femoral venous double-lumen hemodialysis catheter placed - HD started

Labs:

AST, ALT after 10 hours

CHEST SINGLE VIEW Postop day 3:● Essentially unchanged left-sided infiltrates. ● Small bilateral pleural effusions. ● Rounded area of mildly consolidative

atelectasis/infiltrate in the right perihilar and basilar location.

● likely lap sponge overlying the inferiorsternum.

Some new Assessments on postop day 3:Postoperative cardiogenic shock, requiring vasopressorsPostoperative respiratory failure requiring mechanical ventilatory support. Acute renal injury requiring daily hemodialysis.Postoperative ischemic hepatitis.Chronic atrial fibrillation. Leukocytosis.Postoperative thrombocytopenia.

Day 14, 15, Postop day 4, 5:The patient remained fairly stable on milrinone and dobutamine and epinephrine drips. Vasopressin has been on and off. Remains on dialysis.He was taken back to the OR, to clean of the left pleural space and see if closure is possible. Operative report: Mediastinal exploration and sternal closure

Returns to the SICU intubated and sedated. The sternum was closed; a negative pressure dressing was placed over the skin. Continues to be on Flolan, Hemodynamics stable on the Amiodarone, dobutamine, epinephrine, milrinone, Precedex, and vasopressin. HIT ELISA negative 11/25

Day 16 - 18 Postoperative day 6-8:Hemodynamically, he seemed to be tolerating sternal closure reasonably well.Clinically, remained in anasarca despite of daily hemodialysis Platelets trend:His liver function was getting worse with a bilirubin up to 11.6. hematologist was consulted for persistent thrombocytopeniaRecommendations: majority of his thrombocytopenia is due to peripheral destruction from intra-aortic balloon pump - IABP removed

Day 19 Postop day 9:Pt remains intubated, failed SIMV 'trial', Pulmonary consult made, respiratory culture obtainedStill requiring vasopressorsRUQ US for persistently elevated LFTsRemains on daily HDEmpirically receiving Vanc and CeftazidimeImproved thrombocytopenia, not actively bleeding

US abdomen:Gallbladder is normal in size. There is a moderate amount of sludge within the gallbladder, this may be secondary to fasting. There is slight gallbladder wall thickening, this is nonspecific. The bile ducts are normal. Small right pleural effusion.

Day 20 - 27 Postop day 10-17:Started on TPN as not tolerating tube feedings very well Continued to have leukocytosis, respiratory culture grew Klebsiella pneumoniae and a diagnosis of tracheobronchitis made, Continued on IV ceftazidime, planned for tracheostomy later that weekBlood culture remained negativeAlso had loose bowel movements after suppository, C diff was negative.Tunneled dialysis catheter was placed into the right internal jugular vein for dialysisBP remained low requiring pressor support, CVP remained elevated at 15-17 mmHg. ceftazidime changed to ceftriaxone later in the week due to persistent low-grade temperature and worsening leukocytosisLater linezolid and micafungin was added as patient was at risk for nosocomial bloodstream pathogens.Percutaneous tracheostomy was placed on day 24, postop day 14 for his inability to wean from mechanical ventilationLater in the week, His pressor support requirement decreased and he received epinephrine only during hemodialysis.Repeat Echo: Distal septal, anteroapical and apical dyskinesia and LVEF reduced

Day 28 - 31, Postop day 18 - 21:Overnight developed abdominal distention, KUB - diffuse dilatation of intestine consistent with ileus.Zyvox was discontinued and course of ceftriaxone completedMicafungin discontinued due to severe jaundice and hepatocellular dysfunction. Right upper quadrant USG repeated: No evidence for main hepatic or portal vein thrombosis, 2.5 cm complex right renal cyst, small right pleural effusion, Inadequate visualization of the entire pancreas.Tube feeding restarted on 12/09/2015Pt was off the vasopressors support, LFTs trending down but bilirubin still very high at 33

Additional tests: Ammonia 21Anti smooth muscle IgG - NegativeAntimitochondrial antibody - Negative

Day 32, postop day 22 WBC count - 29.7Chest X Ray - Mild left lower infiltrates and small pleural effusion.C. diff and blood culture remained negativeAs he remained afebrile and in the absence of any source of infection, no antibiotics were started

CT chest abdomen pelvis - due to marked rise in leukocytes and persistently elevated LFTs and bilirubin1. Patchy bilateral pulmonary infiltrates, suggesting infection or low-grade pulmonary edema. There are small bilateral pleural effusions.2. Collapsed gallbladder, without intrahepatic or extrahepatic biliary duct dilation.3. Colonic wall thickening involving the right colon and possibly the sigmoid, nonspecific, possibly seen with colitis. No evidence of bowel obstruction.4. Infrarenal aortic aneurysm.

CT head w/o contrast due to worsening mental status - essentially unremarkable

Day 33 - 34, Postop day 23 - 24 Had hypotension overnight and had to be started on vasopressors WBC - 34.6 Started empirically on broad spectrum antibiotics and Rx for c. diff colitis. Virtually unresponsive to verbal or physical stimuli. Diagnosis of sepsis with sepsis shock was made with suspicion for ischemic colitis. C. Diff remained negative.

Day 35, Postop day 25 Family decided to withdraw care. Code status changed to level 3 comfort care. Levophed was not restarted after the last bag, dialysis was discontinued, ventilator discontinued @ 1952

Day 36, Postop day 26, 12/16/2015 @ 0113 patient expires.

Possible causes of death (Multiorgan failure):

VT/VF intraoperatively: Could not be cardioverted. Replaced on CPB and then successfully converted, (Could not find the time required)Required 8u prbc, 5u FFP, 3u SDP, 10u cryo, Factor 7Significant Hypotension on sternal closure.

Acute on chronic Heart failure:Cardiomegaly with marked left ventricular hypertrophySevere coronary artery disease, involving the native coronary arteries and two of three old vein grafts.Recent coronary bypass grafts were intact and patent.Myocardial infarction:Remote myocardial infarction, small foci.Subacute extensive myocardial infarction (3-6 weeks prior to death), involving the septum and much of the left ventricle.Acute myocardial infarction (approximately 12 hours prior to death), involving the apex.

Respiratory failure:Not able to wean from mechanical ventilationTracheobronchitis with Klebsiella pneumoniaeAutopsy:Patchy bilateral edema and BOOP like changesWell-organized thrombus in a single distal pulmonary artery, but no evidence of clinically significant embolism to the lungs.

Acute Liver failure:Markedly elevated bilirubin level, AST and ALTNo evidence of hepatitis or cirrhosis, and no gross evidence of biliary tract obstruction on autopsy.Cholestasis - likely secondary to ischemic injury and/or a pharmacologic agent.

Acute renal failure:with anuria, hyperkalemia and acidosis requiring daily HD Autopsy: Tubular atrophy and interstitial fibrosis, consistent with ischemic injury

Sepsis with septic shock:Markedly elevated WBCPersistent hypotension requiring vasopressor supportPossible source of infection - Tracheobronchitis with Klebsiella pneumoniaeLactic acidosis, thrombocytopenia, hyperbilirubinemia Multiorgan failure, Glasgow Coma Scale <6C diff and Blood culture remained negative (Pt already received broad spectrum antibiotics)

Concern for Intestinal infarction: No evidence of intestinal infarction on autopsy=============================================================================================================

Thank You=====================================================================================================

Autopsy Findings:Cardiovascular SystemA. Severe coronary artery disease.

1. Remote history of bypass grafting.a. Severe atherosclerotic disease involving the native coronary arteries and two of three old vein

grafts. b. Left inferior mammary artery graft patent.

2. Recent history of bypass grafting.a. New vein grafts intact and patent.

3. Myocardial infarction.a. Remote myocardial infarction, small foci.b. Extensive subacute myocardial infarction (3-6 weeks prior to death), involving the septum and much

of the left ventricle.c. Superimposed acute myocardial infarction (approximately 12 hours prior to death), involving the

apex.B. Severe atherosclerotic disease of the aorta and great vessels.

1. Severe calcific atherosclerosis of the descending thoracic and abdominal aorta.2. Abdominal aortic aneurysm, infrarenal, 5 cm, with narrowing of the aorta distal and immediately proximal to the

aneurysm.3. Narrowing of the renal artery ostia, left mild, right severe.4. Aneurysms of the bilateral subclavian arteries.

a. Status post bilateral subclavian-carotid bypass.b. Status post coil-induced thrombosis of the bilateral aneurysms.c. Status post endovascular aortic repair with stent present in the aortic arch / proximal descending

aorta.C. Cardiomegaly with marked left ventricular hypertrophy.

1. Clinical history of hypertension.D. No significant disease identified in the celiac, superior mesenteric or inferior mesenteric arteries.

II. Respiratory SystemA. Patchy bilateral edema.B. Well-organized thrombus occluding a single small distal artery in the right upper lobe.

III. Hepatobiliary SystemA. Cholate stasis of the liver, consistent with marked/prolonged cholestasis.B. Gallbladder and biliary tract intact and patent.

IV. Genitourinary SystemA. Tubular atrophy and interstitial fibrosis, consistent with ischemic injury.B. Benign right renal cortical cyst, approximately 2 cm.