John Martinelli, MSIII, SGUSOM DATE: 7/30/13 Case 04. Rotation: Surgery/Vascular Identifying Data: Ms. LA is a 77-year-old, English speaking, African-American lady who presented to the NBIMC ED via EMS on 7/10/13. DOB: 9/22/35. On arrival she was accompanied by her friend and neighbor, however, Ms. LA was not able to communicate due to intubation by the EMS team. Chief Complaint: Upon visiting Ms. LA, her neighbor stated she appeared very weak, began wheezing, and was having extreme difficulty breathing and speaking, as well as sweating profusely. History of Presenting Illness: On the morning of 7/10/13, a visiting neighbor immediately called 911 when she realized Ms. LA was having difficulty. EMS arrived and found Ms. LA to be severely dyspneic, diaphoretic, and in acute respiratory failure. She did not complain of chest pain. At that time, Ms. LA denied any previous intubation and denied a history of cardiac disease such as CHF or CAD. However, she indicated she has been treated for hypertension but had not been taking her medication for “years”. She was immediately intubated and mechanically ventilated before being transported to NBIMC ED. Upon arrival, she was additionally stabilized with IV Midazolam 50mg/50ml @ 4mg/hr + NS. Past Medical/Surgical History: Uncontrolled hypertension with poor compliance. Knee surgery approximately 1993. Does not recall which knee or the reason. Medications: None. Allergies: NKDA/NKA. Family History: Mother and Father with hypertension. Social History: No history of alcohol, smoking, or drug abuse. No history of STD’s. Physical Exam (ED): Vitals: 98.5, 77, 16, 237/94, 100% (Intub) General: Level 5 Ramsay Sedation with Midazolam. Sluggish response to auditory stimuli and glabellar tap. Skin: Normal. Eye: PERRLA (-)APD. HENT: Normocephalic. Hearing diminished (Sedated). Intubated. Pulmonary: Breath sounds equal but decreased at base b/l. Symmetric chest wall expansion with mechanical ventilation.

Gastrointestinal: Soft. Bowel sounds present and normal. Genitourinary: Foley with good output. Musculoskeletal: Normal appearance. Neurologic: Sedation with Midazolam. Hematologic: Deferred -> Labs Endocrine: Deferred. Psychiatric: Sedation with Midazolam. Labs: WBC: 12.7* Hgb: 14.7 Hct: 44.2 Plt: 335 Na: 146* K: 3.2* CO2: 29 Cl: 106 Cr: 1.01 BUN: 18 PT: 10.0* PTT: 26 INR: 0.9 Review of Systems: Patient sedated. Prior to admission, Ms. LA denied a history of prior intubation or cardiac disease. She was aware of her hypertension but was not taking medication. She recalled having knee surgery in approximately 1993 but does not remember which knee or for what reason. Imaging/Additional Procedures: Day of Admission/ED: ECG: Normal sinus rhythm with left ventricular hypertrophy. Chest XR: Revealed bilateral pulmonary edema. In-Patient CCU Day 3: Stress (Dobutamine) ECG: No evidence of ischemia. Normal heart rate and blood pressure response. Troponin (-). Chest XR: Shows resolving pulmonary edema. In-Patient Telemetry Unit Day 4: Vitals: 98.9, 52, 19, 150/40, 100% (Rm) Labs: WBC: 7.5 Hgb: 11.1* Hct: 34.0* Plt: 260 Na: 143 K: 3.8 CO2: 34

Cl: 101 Cr: 1.36* BUN: 28* PT: 11.6 PTT: 28 INR: 1.1 Chest: Improved breath sounds at lung bases and clear to auscultation b/l. Right Carotid Bruit detected (by attending Hospitalist). Doppler Ultrasound revealed 80 – 99% Right Carotid Stenosis. Discussion: The premise of this discussion is to emphasize the importance of routinely examining the carotid arteries for evidence of bruit – despite a clinical scenario which it may seemingly be unnecessary. Ms. LA had already been downgraded to the telemetry unit pending discharge. The ease at which she could have been discharged without listening for bruit and/or detecting significant carotid stenosis only magnifies the significance of the hospitalist’s finding. With regard to her presenting illness, Ms. LA represents a classic example of left ventricular hypertrophy with congestive heart failure progressing to pulmonary edema with respiratory failure due to uncontrolled chronic hypertension. During her admission, Ms. LA’s hypertensive urgency and respiratory failure was eventually controlled with maximum diuresis and anti-hypertensive therapy. This included hydrochlorothiazide for diuresis in addition to losartan, hydralazine, metoprolol, and clonidine. After approximately 3 – 4 days of treatment, Ms. LA demonstrated marked improvement with respect to her hypertension and pulmonary function. Her blood pressure reduced to 150/40 along with resolving pulmonary edema on repeat chest XR. Breath sounds were improved at her lung bases as well as evidence of non-labored respiration. At this time however, her renal function began to show some sign of probable pre-renal azotemia with a BUN/Cr ratio at 28/1.36. Of course her blood pressure, renal, cardiac, and pulmonary function will need to be closely monitored and controlled under the appropriate specialist’s care. With left ventricular hypertrophy and CHF, it is interesting to note that her stress ECG was normal along with negative troponin findings. This suggests no evidence of myocardial infarction and/or coronary artery disease. In this case, carotid bruit is related to significant carotid stenosis of 80% - 99% detected in an asymptomatic patient with respect to neurologic symptomatology. Upon questioning at the time of Doppler US, Ms. LA denied any history of transient ischemic or permanent neurologic deficit. Classic examples related to carotid stenosis are dependent on the path of embolic obstruction. This includes temporary or permanent loss of speech (fluent or afluent aphasia), contralateral hemiparesis or hemiparalysis, contralateral sensory deficits, as well as ipsilateral visual field loss (amaurosis fugax secondary to branch or central retinal artery occlusion). In contrast to Ms. LA’s findings suggesting lack of coronary artery disease, a 2011 article in the Journal of the American College of Cardiology reported the severity of carotid artery stenosis and the extent of coronary artery disease were significantly correlated. Independent predictors of severe carotid artery stenosis were the presence of left-main or 3-vessel CAD, increasing age, a history of stroke, smoking status, and diabetes mellitus.* Other than her age, none of these risk factors were applicable in this case. Most recently, a 2013 article in Heart and Vessels is more in line with our patient’s clinical picture. It showed that the presence of LVH (with higher epicardial adipose tissue thickness) improves prediction of carotid plaques in hypertensive patients with 0–1 additional risk factors. However, those with ≥2 risk factors show high prevalence of carotid plaques independently of LVH and/or epicardial adipose thickness.** In this context, Ms. LA’s systemic history of LVH , HTN, and increased age can be considered predictive for carotid plaques leading to significant carotid stenosis.

Differential Diagnosis: A carotid bruit is most commonly associated with carotid artery stenosis, however, a murmur referred from the heart can occur. Assessment:

1. Severe asymptomatic right-sided carotid artery stenosis probable secondary to long-standing uncontrolled hypertension. LVH and age may be associated risk factors.

2. LVH, CHF, pulmonary edema, and respiratory failure probable secondary to long-standing uncontrolled hypertension.

Pathophysiology Atherosclerotic plaque formation with carotid stenosis usually occurs at or near the carotid bifurcation. Plaque formation occurs due to vascular endothelial damage, lipid triggered oxidative stress, smooth muscle proliferation, with risk of ulceration and/or release of embolic debris possibly leading to neurologic sequelae. Clinical Features Transient Ischemic Attack(s) (TIA’s) or permanent Cerebrovascular Accident (CVA) secondary to carotid stenosis can manifest with neurologic signs and symptoms such as:

-­‐ Contralateral hemiparesis/hemiparalysis -­‐ Contralateral sensory deficit -­‐ Fluent or afluent aphasia -­‐ Ipsilateral visual field loss (amaurosis fugax) -­‐ Others (depending on location of embolic obstruction)

Diagnosis: Clinical signs and symptoms can lead to suspicion of carotid stenosis. However, as this case demonstrates, asymptomatic severe disease is possible. Therefore, diagnosis can be achieved via routine practice of carotid examination for bruit even without symptomatology or associated risk factors. Of course, in the presence of certain neurologic deficits, carotid stenosis must be investigated. Definitive diagnosis is obtained by imaging with Doppler Ultrasound being the trusted and least invasive technique. Carotid velocity ratios are calculated which yield an estimation of degree of stenosis. The gold standard for diagnosis is direct angiography with contrast. However, because of the invasiveness and possible patient sensitivity to contrast material, angiography is rarely used. Other techniques include CT and MRI angiography. Treatment Surgical Carotid Endarterectomy (CEA), stent placement, as well as non-surgical approaches can be considered depending on the degree of stenosis and symptoms. With respect to indications for CEA, two landmark studies are often referenced: Symptomatic:

-­‐ One or more transient ischemic attacks (TIAs) in the preceding 6 months and carotid artery stenosis exceeding 50%.

-­‐ Ipsilateral TIA and carotid artery stenosis exceeding 70%, combined with required coronary artery bypass grafting (CABG).

-­‐ Progressive stroke and carotid artery stenosis exceeding 70% Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. Aug 15 1991;325(7):445-53.

Asymptomatic:

-­‐ “Good Risk” Patients with > 60% Stenosis Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. May 10 1995;273(18):1421-8. Regarding stent placement, the risk of embolic events has been found to be greater in comparison to CEA, therefore CEA remains the first surgical option in most clinical scenarios. Medical management includes control of underlying risk factors. Recent evidence has shown adding statins to the treatment plan may have vascular endothelial protective effects in addition to lowering cholesterol. Risk Factors Atherosclerotic factors:

-­‐ Hypertension -­‐ Diabetes -­‐ Hyperlipidemia/Hypercholesterolemia -­‐ Smoking -­‐ EtOH -­‐ CAD -­‐ LVH (with </= 1 risk factor) -­‐ Turbulence at carotid bifurcation

Complications Complications of carotid stenosis and/or lack of appropriate treatment can be variable including asymptomatic disease, transient ischemic events, cerebrovascular accidents with permanent neurologic deficits, and even death. In the presence of patent collateral circulation from the contralateral carotid arterial supply, the risk of these events is reduced. Likewise, significant stenosis in the contralateral carotid is associated with increased morbidity and mortality. With respect to CEA surgery, similar complications can occur during and/or post surgery due to possible release of embolic debris, ulceration, or surgical failure. In the case of acute carotid occlusion, emergent CEA is generally not recommended due to possible reperfusion injury and hemorrhagic CVA. Plan: Ms. LA was scheduled for right CEA on 7/22/2013 as an outpatient at NBIMC SDS. She did require a graft/patch angioplasty and tolerated the procedure well without complication. There was no evidence of post-operative neurologic deficits. Regarding her initial presentation, current cardiopulmonary status, as well as renal status, the importance of follow-up and treatment with her appropriate specialists was stressed.

References: * J Am Coll Cardiol. 2011;57(7):779-783. doi:10.1016/j.jacc.2010.09.047 ** Heart and Vessels. May 2013, Volume 28, Issue 3, pp 277-283