CDM II Exam 2 Study Guide.docx

Exam Date: Wednesday, July 12, 2023 Topics: Heart Failure, Obesity/Metabolic syndrome, Pulmonary Hypertension, Pain Management, Rheumatoid arthritis, Gout, Migraine Heart Failure- Dr. Lancaster (6/8-6/12) Heart failure = pump failure, results from a disorder that affects the heart’s ability to contr...

Exam Date: Wednesday, July 12, 2023 Topics: Heart Failure, Obesity/Metabolic syndrome, Pulmonary Hypertension, Pain Management, Rheumatoid arthritis, Gout, Migraine Heart Failure- Dr. Lancaster (6/8-6/12) Heart failure = pump failure, results from a disorder that affects the heart’s ability to contract (systolic function) or fill/relax (diastolic function) which results in tissues not adequate perfused to meet the demands of the body Systolic failure: thin heart walls Diastolic failure: thick heart walls Definition: a syndrome caused by cardiac dysfunction, generally resulting from myocardial muscle dysfunction or loss and characterized by left ventricular dilation or hypertrophy, leads to neurohormonal and circulatory abnormalities usually resulting in symptoms such as fluid retention, SOB, fatigue The heart as a cup Systolic failure: the cup (ventricle) is full but the person drinking from the cup can only take small sips, so the person (organs) remain thirsty Diastolic failure: the cup (ventricle) can only be filled halfway and the person can drink it as one big gulp, but the person (organs) remains thirsty Systolic HF = HFrEF (heart failure with reduced ejection fraction, EF < 40%) Diastolic HF = HFpEF (heart failure with preserved ejection fraction, EF > 50%) HF with mid-range EF = HFmEF (EF between 40-49%) HF with recovered EF = patient with reduced EF in the past but now improved EF > 50% Stage Classification Definition A At risk for heart failure No prior or current symptoms, cardiovascular changes, biomarkers B Pre-heart failure No prior or current symptoms Presence of one of the following: structural heart disease, abnormal cardiac function, elevated natriuretic peptide, or cardiac troponin C Symptomatic HF Prior or current symptoms of HF due to structural or functional cardiac abnormalities D Advanced Severe symptoms of HF at rest, recurrent hospitalizations, refractory or intolerant to GDMT, requires assist device or transplantation, palliative care NYHA Class I-IV Class I: asymptomatic Class II: symptomatic with moderate exertion Class III: symptomatic with minimal exertion Class IV: symptomatic at rest Heart Failure Prevention Maintain BP at desired target (usually 130/80) Control DM and lipids A1C 7-7.5 showed less severe HF/comorbidities compared to 8-8.5 Aerobic exercise 20-30 minutes 3-5x per week BMI < 30 Stop smoking Sodium intake less than 2-3 grams/day Limit alcohol to 1-2 drinks per day (men) and 1 drink/day (women) Cardiac Output (mL/min) = heart rate (HR in beats/minute) * stroke volume (SV in mL/beat) Four determinants for CO are heart rate, preload (volume of blood entering the ventricles, proportional to CO), afterload (resistance that the ventricles must overcome to circulate blood, inverse relationship with CO), and contractility (how hard the muscles contract to pump blood out of the heart, proportional to CO) Heart Failure is an adaptive/maladaptive state Initial insult to stroke volume can be ischemic cardiomyopathy (Post-MI) or non-ischemic myopathy (genetic disorders, alcohol-induced, adriamycin-induced, viral disorders, valvular disease such as stenosis or regurgitation) These initial insults can lead to the adaptive/maladaptive state The body adapts to the low cardiac output by releasing neurohormones Chronic neurohormone release leads to maladaptation (remodeling of ventricular and vascular tissue) Results in a progressive syndrome CO = rate of travel, damage to one side of the heart causes a decrease in rate of oxygen delivery to tissues, the normal rate of travel is 5-7 L/min Decreased CO is thought to be (by the body) a result of decreased blood volume/sodium, which is sensed by receptors in blood vessels and baroreceptors. This causes the release of norepinephrine Norepinephrine: increases B1 activity which causes an increase in HR due to increased contractility, stimulates myocytes for ionotropic effects. Will cause the release of renin from the juxtaglomerular cells in the kidney to stimulate RAAS. RAAS System (renin-angiotensin-aldosterone): stimulates the conversion of Angiotensin 1 to Angiotensin 2 via ACE, causes vasoconstriction to shunt blood to vital organs Angiotensin 2 causes vasoconstriction and increased preload via aldosterone/vasopressin Aldosterone increases volume by retention of sodium and water in the kidneys, which increases preload The modulation via neurohormones ultimately causes an increased CO and BP, which is modulated via BNP Natriuretic Peptides (ANP and BNP) BNP is secreted by the ventricles in response to wall stress and may be used to detect the presence of or worsening of HF, overall BNP levels increase during HF Promotes natriuresis and diuresis, with other beneficial effects (in HF patients) such as vasodilation Neprilysin: responsible for breaking down natriuretic peptides into inactive fragments Inhibition of neprilysin increases BNP concentrations (also bradykinin and substance P) Angiotensin 2 is a substrate for neprilysin, so an angiotensin 2 targeting agent is required for co-administration (ARBs) Neurohormone Maladaptive Response Norepinephrine Down regulation of the beta receptor, arrhythmias Angiotensin 2 Loss of flow-mediated vasodilation, thickening and rigidity of arteries, and increased afterload Aldosterone (and vasopressin) Mechanical stress of the heart from too much preload, thickening of the left ventricle, apoptosis of left ventricle endothelial cells Endothelin Hypertrophy of smooth muscle cells in vasculature, fibrotic changes These neurohormones help the boyd in the short term but long term will cause myocardial and vascular remodeling and worsening of HF Risk factors for development of HF: advanced age, male gender, african american race, family history of cardiomyopathies, diabetes, hypertension, hyperlipidemia, obesity, lifestyle (smoking, sedentary lifestyle, alcohol, substance use disorder), medications (long term use of anabolic steroids, imatinib, doxorubicin, and itraconazole) H2FPEF Diagnostic- greater than or equal to 6 points is highly diagnostic of HFpEF H2 = heavy (BMI > 30) or on 2 or more antihypertensives BMI is 2 points 2 or more antihypertensives are 1 point F = atrial fibrillation (3 points) P = pulmonary hypertension, PASP > 35 (1 point) E = edler, age > 60 (1 point) F = filling pressure > 9 (1 point) HFA-PEFF Score P = pre-test assessment Signs/symptoms of HF, comorbidities, risk factors, standard echocardiography E = echo and natriuretic peptide score F = functional testing in case of uncertainty (stress test, invasive hemodynamic measurements) F = final etiology (special imaging, biopsies, genetic testing) Guidelines for GDMT for Heart Failure: ACCF/AHA Stage Guideline Recommendation A ACEi or ARB in appropriate patients for vascular disease or diabetes Statins as appropriate B ACEi/ARB Beta-blockers or statins as appropriate for comorbidities In select patients: ICD Revascularization or valvular surgery C HFpEF: Diuresis SGLT2i ARNi/ARB Mineralocorticoid receptor antagonists Guideline driven indications for comorbidities HFrEF: Diuretics ACEI, ARB, or ARNi (sacubitril/valsartan) Beta-blockers MRAs In select patients: Ivabradine Hydralazine/isosorbide dinitrate Digoxin CRT/ICD Revascularization or valvular surgery D Advanced care measures Heart transplant Chronic inotropes Temporary or permanent MCS Experimental drug or surgery Palliative or hospice care ICD deactivation Cornerstone of GDMTs: Beta blockers, ACEi/ARB/ARNi, mineralocorticoid antagonist, SGLT2i Patients must be on these 4 medications for class C heart failure! Drug Contraindications & Precautions Drug Class Contraindications Cautions SGLT2i Type 1 DM Lactation Dialysis Known hypersensitivity Kidney impairment (dapa = eGFR < 25, empa eGFR < 20) Pregnancy Increased risk of mycotic genital infections May contribute to volume depletion/hypotension Ketoacidosis (diabetes, dehydration, or fasting) AKI Necrotizing fasciitis (gangrene) MRA Potassium > 5 Addison disease Pregnancy Known hypersensitivity Kidney impairment (eGFR < 30 or SCr > 2.5) Initiate at half dose if eGFR 30-50 Concomitant use with drugs that increase potassium levels (potassium supplements, ACEi, ARBs, ARNIs, NSAIDs, Trimethoprim) Gynecomastia Lactation ARNI Coadministration within 36 hours of ACEi History of any angioedema Pregnancy Lactation Severe hepatic impairment Known hypersensitivity Use of alirisken in individuals with DM Dose reduce by ½ if: Not currently taking ACEi or ARB or taking a low dose of ACei or ARB Moderate hepatic impairment Renal artery stenosis Hypotension ARB Pregnancy Lactation Concomitant use with ACEi, alirisken, or ARNi Known hypersensitivity Renal artery stenosis History of angioedema Hyperkalemia Hypotension AKI Guideline Steps Establish diagnosis of HFrEF, address congestion, and initiate GDMT HFrEF, EF < 40% (stage C) ARNi/ACEi/ARB ARNi in Class 2-3 ACEi or ARB in Class 2-4 Beta Blocker MRA SGLT2i Diuretics, as needed Titrate to target dosing as tolerated, labs, health status, and LVEF LVEF < 40%, persistent HF LVEF > 40%, HFimpEF (stage C) Continue to use GDMT with serial reassessment and optimize dosing, adherence, patient education, address goals of care Consider these patient scenarios Class 3-4, african american patient Hydral-nitrates Class 1-3 with LVEF < 35% and greater than 1 year survival ICD Class 2-3 (or ambulatory Class 4) with LVEF < 35% CRT-D Implement additional GDMT and device therapy as indicated Reassess symptoms, labs, health status, and LVEF Refractory HF (Stage D)- move to step 6 Symptoms improved Referral for HF specialty care or additional therapy Durable MCS, in select patients Cardiac translate Palliative care Investigational studies Treatment Algorithm for HFrEF Stage C Initial: ARNI/ACEi/ARB (ARNI preferred) + evidence based beta blocker + diuretic agent as needed Then, Aldosterone antagonist Patients with eGFR > 30 SCr < 2.5 (males) or 2 (females) K < 5 Class 2-4 SGLT2i Patients that meet eGFR criteria Class 2-4 Diuretic agent For patients with persistent volume overload Class 2-4 Hydralazine + isosorbide dinitrate For persistently symptomatic black patients despite ARNI/beta-blocker/aldosterone antagonist/SGLT2i Class 3-4 Ivabradine For patients with resting HR > 70 on maximally tolerated beta-blocker dose in sinus rhythm Class 2-3 Dosing Drug Initial Daily Dose Target Dose Lisinopril 2.5 to 5 mg once daily 20 to 40 mg once daily Losartan 25 to 50 mg once daily 50 to 150 mg once daily Valsartan 40 mg twice daily 160 mg twice daily Sacubitril/valsartan 49/51 mg twice daily (can be initiated at 24/26 mg twice daily) 97/103 mg twice daily Carvedilol 3.125 mg twice daily 25 to 50 mg twice daily Metoprolol succinate (ER) 12.5 to 25 mg once daily 200 mg once daily Spironolactone 12.5 to 25 mg once daily 25 to 50 mg once daily Dapagliflozin 10 mg once daily 10 mg once daily Empagliflozin 10 mg once daily 10 mg once daily Isosorbide dinitrate/Hydralazine 20/37.5 mg three times daily 40/75 mg three times daily Treatment Guideline for HFpEF Initial: SGLT2i Then, Loop diuretic agent For individuals with fluid retention Class 2-4 MRA For all women Men with EF < 55-60% Patients with fluid retention ARNi For all women Men with EF < 55-60% ARB For ARNi-eligible individuals who cannot take due to cost or intolerance Initiating and/or titrating therapy, before making any changes: Assess physical findings: signs and symptoms of congestion (SOB, peripheral edema, gut edema, CXR, S3) This is NOT an optimal time to initiate or titrate beta-blockers Assess physical findings: signs and symptoms of low perfusion (activity level, BP, kidney function, cognitive function, warm/cold to touch) Assess labs: kidney function (BUN or SCr), urine output, BNP, H & H, serum sodium, and EKG Assess compliance and drug allergy history Assess recent history: any new medications or lifestyle issues that interfere with management Guidelines recommend titrating doses in 2 week intervals until at maximum tolerated dose and/or target dose achieved Magnitude of Benefit of Therapy options Medication RR reduction in mortality (%) RR reduction in hospitalizations (%) SGLT2i 14-27% 20-31% ACEi/ARB 17% 31% Beta-blocker 34% 41% Aldosterone antagonists 30% 30% SGLT2i’s Dapagliflozin (Farxiga) and empagliflozin (Jardiance) have both been approved for use in patients with or without type 2 diabetes These agents have demonstrated reductions in cardiovascular death and hospitalizations due to HF, including additive benefit with MRAs and ARNi Recent findings show potential benefit in patients over 65 with arterial “stiffness” due to reduction in oxidative stress and improved endothelial function Guidelines: Recommended for any patient with HFpEF without contraindications Dosing: 10 mg daily for both dapagliflozin and empagliflozin eGFR cutoffs: Dapagliflozin < 30 mL/min Empagliflozin < 20 mL/min Why does it work? Reduction in glucose reabsorption causes a reduction in preload via natriuresis/diuresis. It also causes a reduction in afterload via reduction in arterial pressure. Inhibition of the sodium-hydrogen exchange in cardiac tissue reduces hypertrophy, remodeling, and fibrosis. They also stimulate glucagon production, which increases the cardiac index and alternative energy supply. Mineralocorticoid Receptor Antagonists (spironolactone and eplerenone) These agents will antagonize the effects of aldosterone on ventricular remodeling NOT used for diuretic effects Cautions: avoid if GFR < 30 mL/min or potassium > 5 Can initiate at half dose of the eGFR is 30-50 ml/min Guidelines: recommended in patients with Class 2-4 systolic HF (EF < 35%) unless contraindicated Characteristic Spironolactone Eplerenone Potency ++; non-selective antagonist on mineralocorticoid and progesterone, androgen receptors +; selective antagonist on mineralocorticoid receptor in the kidney, heart, and vessels Target Dose 25-50 mg daily 50 mg daily Studies RALES, TOPCAT EPHESUS, EMPHASIS Side effects Gynecomastia, increased K+ Increased K+ Cautions Hyperkalemia and CKD Hyperkalemia and CKD ARNI/ACEi/ARB Benefits of these classes have been found to help with maladaptive changes (including remodeling) post-MI Additional benefits have been noted in reducing rates of mortality, hospitalization, and progression to severe/advanced HF Stage 2-3: ARNi recommended Stage 2-4: ACEi/ARB recommended ARNi is preferred but ACEi can be used if ARNi is unavailable, not tolerated, or not affordable ARB is the last choice of the 3 agents (can be used if ACEi is unavailable, not tolerated, or unaffordable) Entresto (Sacubitril + Valsartan) MOA: inhibits Neprilysin’s action on BNP and Angiotensin 2, as well as inhibiting the action of Angiotensin 2 on the angiotensin 1 receptor Indication: class 2-4 chronic heart failure Starting dose: 49/51 mg twice daily Reduced starting dose 24/26 mg twice daily Used in patients with no prior ACE-i or ARB use or prior low dose of these medications Can also be used in severe renal impairment Target dose: 97/103 mg twice daily Contraindications: history of angioedema related to prior ACEi or ARB, coadministration with ACEi within 36 hours (risk of angioedema), concomitant use of alirisken in diabetic patients Guidelines: in patients with chronic symptomatic HFrEF Class 2 or 3 who tolerate ACEi or ARB, replacement with ARNi is recommended to reduce mortality and morbidity Patients must: tolerate an ACEi/ARB for 4 weeks, have recent hospitalizations for HF, and have no history of angioedema ACEis: no difference seen among the available ACEis Cough- 20% of patients Caution with angioedema Monitor potassium and renal function Guidelines: recommended for prevention and treatment of HF, beneficial for patients with current or prior symptoms of HFrEF to reduce morbidity and mortality Beta-blockers (Bisprolol, carvedilol, or SR metoprolol succinate) Should be used in all patients with reduced (systolic) LVEF to prevent symptomatic HF HFpEF: should be reserved for patients with special indications (prior MI up to 3 years ago, angina, and atrial fibrillation) Bisoprolol Carvedilol Metoprolol Selective B1 blocker Non selective beta-blocker with alpha receptor blockade Selective B1 receptor blocker Least lipophilic Take with food Released over 20 hours Most bioavailable May increase digoxin levels May be preferred if BP is marginal Target dose = 10 mg once daily Target dose = 25 to 50 mg twice a day Target dose = 200 mg once daily Only use bisoprolol, carvedilol, or metoprolol succinate Initiate at low doses and titrate every 2 weeks, reach optimal dose in 8-12 weeks Only initiate and/or titrate when the patient is stable (no acute dyspnea or fluid overload or need for compensatory HR) Monitor HR- caution if HR < 55 BPM Diuretics: recommended in patients with systolic HF and evidence of fluid retention to improve symptoms Not all patients are congested! Loop diuretics are the gold standard Thiazide diuretics (hydrochlorothiazide or metolazone) may be added to loop diuretics for diuretic resistance Furosemide is the most commonly prescribed loop diuretic Torsemide has increased oral bioavailability, longer half life, and beneficial effects on myocardial fibrosis, aldosterone production, sympathetic activation, ventricular remodeling, and natriuretic peptides Diuretic resistance: switch to a different diuretic, increase loop diuretic dose, lower dietary sodium intake (below 2 g), consider fluid restriction, minimize drug/drug interactions (NSAIDs), IV administration, sequential nephron blockade Loop diuretics Sulfa allergies: ethacrynic acid preferred (or bumetanide) Dosing: titrate to intake + output and body weight Initial goal: net loss of 500 mL to 1 L per day Split the daily dose for maximal effect Monitor renal function, potassium, magnesium, and sodium Monitor for gout attacks in susceptible patients Advise patient to monitor urine frequency and color Medication management: weight diaries, diuretic sliding scales, compression stockings, leg elevation Other medications used in HF: nitrates + vasodilator therapy, digoxin, ivabradine, and vericiguat Oral Nitrates and Hydralazine Combination is recommended to reduce mortality in self-described african american patients with Class 3-4 receiving optimal therapy with ACEi and beta-blocker unless contraindicated May be considered in non-african american patients with HFrEF and remain symptomatic despite optimized standard therapies Can also be used in place of ACEi or ARB in intolerant patents or those with significant renal dysfunction precluding use of ACEi/ARB Ivabradine (Corlanor) Approved to reduce hospitalizations in patients with stable HF and EF < 35%, a resting HR of at least 70 BPM on maximally tolerated beta blockers Used in patients with COPD and/or hypotension who cannot tolerate maximal beta-blockade 2.5 mg to 7.5 mg twice daily added to GDMT MOA: only works at the SA node to slow HR and does not actually provide adrenergic blockade Digoxin No effect on mortality, but reduces hospitalization rate Most beneficial in patients with lower EF and Class 3-4 patients MOA: neurohormonal modulator, increases parasympathetic and baroreceptor sensitivity and a weak inotrope, can decrease HR via vagal effects and has a role in atrial fibrillation Cautions: dosed per renal function and age 0.125 mg daily or every other day for those over 75, impaired renal function, or low BMI Target serum concentration is 0.5-0.9 ng/mL Vericiguat: Guanylyl cyclase inhibitor MOA: binds to guanylyl cyclase which then increases the concentrations of cyclic guanosine monophosphate. This induces vasodilation, decreases cardiac remodeling.fibrosis, and improves endothelial function Used in patients Class 2-4 on GDMT still experiencing elevated BNP levels (over 300) or pro-BNP levels (over 1000) Initial dose: 2.5 mg once daily Take with food Titrated based on systolic BP Target dose: 10 mg once daily Caution: do not use with nitrates or PDE-5i because it will increase risk of hypotension Patients with HF should receive specific education to facilitate HF self-care, including an action plan that mentions changes in breathing, weight gain, new or worse swelling, changes in ability to do everyday things Drug interactions that may worsen HF Non-selective NSAIDs COX-2 selective inhibitors Thiazolidindiones Saxagliptin Alogliptin Flecainide Disopyramide Sotalol Dronedarone Doxazosin Diltiazem Verapamil Nifedipine Reinforce Fluid Restriction: 1.5-2 L per day is reasonable in Stage D to reduce congestion Devices & HF Implantable cardioverter-defibrillator (ICD): prevents sudden death in patients with previous cardiac arrest or sustained ventricular arrhythmias Ventricular assist devices (VAD): bridge to transplantation, left ventricular or biventricular support, requires long term anticoagulation Pain & HF 75% of patients with advanced HF experience pain NSAID use is CONTRAINDICATED Local treatments such as hot/cold therapy and PT may help Opiates can be considered in patients with advanced HF and pain when other therapies are not adequate Comprehensive assessment of pain and risk Set functional goals Start lower, go slower (tablet formulations often do not come in low enough doses, so a solution must be used) Add bowel regimen Monitor! Fatigue & HF: associated with both the psychological and physiological consequences for HF May be a result of decreased CO, elevated proinflammatory mediators, deconditioning, sleep impairment, depression, anxiety Cardiac rehabilitation is safe and has been shown to improve clinical status and outcomes Anorexia/Cachexia & HF Anorexia, weight loss, and malnutrition are common in advanced HF After optimization of therapy, manage major contributors to anorexia such as nausea, depression, constipation, dyspnea, and taste alteration Refer patients to a dietitian, artificial nutrition has not been shown to improve survival in patients with HF Nausea & HF 50% of patient report nausea in the last 6 months of their life Treatment should focus on reversal of contributors, optimizing volume status, trial of PPI or antacids, elimination of contributing medications if possible, consider antiemetics for vomiting (watch QTc prolongation) Depression & HF Depression in patients with HF is 2-3x higher than the normal population Depression is an independent predictor of mortality in HF Use SSRIs or SNRIs in patients with HF, avoid QTc prolonging agents Patients should be screened regularly for depression and anxiety Acute Decompensated Heart Failure (ADHF): new or worsening signs or symptoms of heart failure that are usually caused by volume overload and/or hypoperfusion and lead to additional medical care “Exacerbation of Heart Failure” Mechanism of ADHF: Excessive neurohormone release Angiotensin 2 (vasoconstriction, rigid vessels): increase in afterload Aldosterone (sodium and water retention): increased preload Norepinephrine (sympathetic stimulation): increase in renin release, attempt to increase contractility, increased HR Vasopressin (increase in water retention): increase in preload Counter-regulatory hormones (such as BNP, NO, bradykinin) are overwhelmed Symptoms of ADFH: dilated pupils, pale or gray skin, dyspnea, orthopnea (cannot breathe unless sitting up), crackles/wheeze, cough, decreased blood pressure, nausea, vomiting, ascites, pitting edema, anxiety, falling O2 saturation, confusion, jugular vein distention, infarct, fatigue, tachycardia, enlarged spleen and liver, decreased urine output, weak pulse, cool skin Subsets of ADHF: Patients having symptoms of HF for the first time- de novo disease (25%) Patients with exacerbated symptoms of established HF (70%) Could be from non-compliance or added stress (diabetes, infection) Patients with advanced or end-stage (5%) Precipitating Events/Factors Disease progression Cardiac remodeling leading the reduced ejection fraction Acute physiologic stress Arrhythmias, infection, anemia, MI, valvular heart disease, pulmonary disorders, VTE, rheumatologic disorders, uncontrolled thyroid disorder, uncontrolled diabetes, ARF, etc Changes in nutrition Salt restriction Fluid restriction Fat intake Harmful medications Glucocorticoids, NSAIDs, glitazones, non-DHP CCBs Cocaine, alcohol, tobacco Treatment goals Improve symptoms, especially congestion and low output states quickly Optimize volume status Identify etiology Identify precipitating factors Optimize chronic oral therapy Minimize side effects Educate patient and family “Wet” or “Dry” ADHF Refers to the level of congestion (volume overload) Symptoms of “Wet” = orthopnea, shortness of breath Signs of “Wet” = distended internal jugular vein, S3 heart sound, pulmonary rales, resting tachycardia, peripheral edema “Warm” or “Cold” ADHF Refers to the level of perfusion Signs of “Cold” = worsening renal function, altered mentation, hypotension (low MAP), tachycardia, metabolic acidosis, cyanosis, cold or cool extremities Mean Arterial Pressure (MAP) Average pressure in arteries during one cardiac cycle, a better indicator for perfusion to vital organs Ideally MAP > 65 MAP = [(DBP * 2) + SBP] /3 Cardiac Index (CI): an assessment of the CO based on the patient’s size CI = CO / Body surface area (BSA) Normal range: 2.5 - 4 Poor perfusion is generally below 2.2 Forrester Classification Cold and Wet (Low perfusion, high congestion) Also known as cardiogenic shock Normal BP: vasodilators Low BP: inotropes or vasopressors Cold and Dry (Low perfusion, low congestion) Also known as Hypovolemic shock Fluid administration Warm and Wet (High perfusion, high congestion) Diuretics or vasodilators (nitroglycerin, nitroprusside) Warm and Dry (High perfusion, low congestion) Normal state Natriuretic Peptide: Atrial (ANP) and B-type (BNP) BNP is secreted by the ventricles in response to wall stress due to volume overload BNP can be used to detect the presence of or worsening of HF, levels generally increase in HF Natriuretic peptides promote natriuresis and diuresis Can have multiple other good effects in HF patients BNP Elevation = ADHF BNP < 100 is strongly suggestive that it is NOT ADHF BNP > 400 suggests that ADHD is occurring, but it can be falsely elevated in CKD, AF, and pulmonary hypertension BNP may be falsely low in obese patients and patients with HFpEF Key principles for treatment of ADHF Continue, initiate, and further optimize GDMT Beta blockers: consider reducing or temporarily discontinuing a beta-blocker in those patients with significant volume overload or low cardiac output, especially those who require inotropic support while hospitalized GDMT should not be stopped for mild or transient reductions in BP ARNI Management of ADHF: evidence shows benefit over valsartan to reduce death, hospitalizations, and outpatient visits Management of “Wet” patients (fluid overload) Diuresis (bolus > continuous infusion) No different in agent of use May consider addition of metolazone or spironolactone is lack of control Guidelines: if patients are already receiving loop diuretics, initial IV dose should be equal to or exceed the chronic oral daily dose and be given as intermittent bolus or infusion Diuretic naive = 20-40 mg IV furosemide, no response double the dose Dosing Conversions Medication PO IV Furosemide (Lasix) 40 mg 20 mg Bumetanide (Bumex) 1 mg 1 mg Torsemide (Demadex) 20 mg 20 mg 40 mg furosemide PO = 1 mg bumetanide PO = 20 mg torsemide PO Lasix IV:PO is 1:2 Bumex IV:PO is 1:1 Demadex IV:PO is 1:1 Typically, double the home dose and assess response in 2-4 hours Is urine output > 500 mL? Urine output ranges from 1-2 liters over 24 hours 1 liter fluid = 1 kg Adverse effects of diuresis: hypokalemia, hypomagnesemia, uric acid, resistance, reflex increase in neurohormones Diuretic Resistance Maximize the dose of IV diuretic Furosemide = 160-200 mg Torsemide = 100 mg Bumetanide = 8 mg Change from IV bolus to continuous infusion Add a thiazide for sequential segmental nephron blockade Consider acetazolamide Ultrafiltration Reasons for resistance: compensatory increase in RAAS, distal tubule hypertrophy, renal insufficiency (needs higher dose), low albumin (needs higher dose), central/abdominal edema Vasodilation (preferred over inotropes) Nitroglycerin is better than nitroprusside Fluid restriction Sodium restriction Compression devices Management of “Cold” patients (low perfusion) Inotropes: dobutamine and milrinone Favored to increase cardiac output to preserve/increase perfusion Guideline: short term continuous IV inotrope support may be reasonable in hospitalized patients presenting with reduced CO to maintain systemic and end organ perfusion Used in patients with systolic dysfunction only! (EF < 40%) Milrinone: phosphodiesterase-3 inhibitor, increases intracellular levels of cAMP, acts on cardiac and vascular tissue, increases CO, positive inotrope/chronotrope, reduced PAP + afterload, causes hypotension, pro-arrhythmic, t ½ = 2.5 hours, accumulation may occur in the setting of renal insufficiency, monitor LFTs and kidney function Dobutamine: works directly on beta cells in cardiac muscle, increases intracellular levels of cAMP, increases CO, minimal effect on MAP, pro-arrhythmic, t ½ = 2-5 minutes, tachyphylaxis requiring increased dose for effect, caution in MAOI, contraindicated with sulfa-allergy Clinical Scenario Preferred Inotrope Increased pulmonary artery pressure (PAP) Milrinone Need for a beta-blockade (arrhythmia while on a beta-blocker) Milrinone Hypotension Dobutamine Renal insufficiency Dobutamine Must consider hypotensive patients, milrinone has been associated with worse outcomes, dobutamine is the treatment of choice in hypotensive patients Inodilator Pressors Mechanical devices (IABP or VAD) If congestion fails to improve Add fluid restriction (< 2 L/day) and sodium restriction (< 2 g/day) Increase loop diuretic dosing to maximum bolus dosing Change to continuous infusion Total daily dose divided into mg/hour, start with 10-20 mg/hour and then increase as needed to 40 mg/hour MAX) Add a second type of diuretic Metolazone 2.5-10 mg, given PO 30-60 minutes prior to loop diuretic Chlorothiazide 250-500 mg, given IV 30 minutes before loop diuretic Ultrafiltration Vasodilators Vasodilators Vasodilators MOA Arterial or Venous? Vasodilation effects Hemodynamics Nitroglycerin Transformed into nitrogen oxides, mimics the effects of nitric oxide, activating intracellular soluble guanylate cyclic GMP levels Primarily venous Reduces preload and pulmonary congestion May lower systemic afterload, increase stroke volume, and CO at higher doses Decrease SBP Decrease PCWP Decrease SVR Nitroprusside Direct relaxation of smooth muscle by activating guanylyl cyclase Both Reduction of afterload and preload Increased CO Decrease SBP Decrease PCWP Decrease SVR Nesiritide Recombinant brain natriuretic peptide Removed from the market due to renal toxicity Both Reduction of afterload and preload Variable effects on CO Decrease SBP Decrease SVR Role in treatment of ADHF: no clear long-term benefits established but can relieve symptoms of dyspnea Consideration for those presenting with signs and symptoms of hypoperfusion or requiring escalation of care Most useful: hypertension, coronary ischemia, pulmonary congestion, mitral regurgitation Nitroglycerin is favored due to lack of comparable risk of hypotension compared to nitroprusside Cardiogenic Shock: persistent hypotension and tissue hypoperfusion due to cardiac dysfunction in the presence of adequate vascular volume SBP < 90 for over 30 minutes Low CI (< 2.2) Elevated PCWP (> 15) Oliguria, cool extremities, and poor mentation Treatment Goals Maintain arterial pressure (MAP) as needed for perfusion Initial treatment are Pressors Epinephrine, Norepinephrine (Levophed), Dopamine, Phenylephrine, Vasopressin Pressor alpha B1 B2 Dopamine Other SBP CO SVR Epinephrine ++++ +++ ++ 0 Increase Increase Increase Norepinephrine ++++ ++ 0 0 Increase N/A Super increase! Phenylephrine ++++ 0 0 0 Increase N/A Increase Dopamine ++ ++ + ++ N/A Increase Increase Vasopressin 0 0 0 0 V1 receptor Increase N/A Increase Dopamine shows an increased risk of death compared to norepinephrine Obesity/Metabolic Syndrome- Dr. Sibicky & Dr. Gonyeau (6/14-6/15) Obesity: excess portion of body fat, 20% or more over normal weight, BMI > 30 Chronic, progressive, relapsing, multi-factorial, neurobehavioral disease Excess portion of body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces Adverse metabolic, biomechanical, and psychosocial components BMI = weight (kg) / height (m2) Obesity is growing and there is concern regarding obese children across america Waist circumference: measurement of waist right above the navel Abdominal obesity (men) > 40 inches or 102 cm Abdominal obesity (women) > 35 inches or 88 cm Advantages: well-correlated to metabolic disease, direct anatomical measure of adipose tissue deposition, increase of waist circumference is associated with tissue dysfunction, low cost Disadvantages: not always reproducible, not superior to BMI in patients with BMI > 35, racial and ethnic differences Hip circumference: measurement of hips at the widest point Waist to hip ratio: more accurate measurement of obesity compared to others Male Female Health risk 0.95 or below 0.8 or below Low 0.95-1.0 0.81-0.85 Moderate risk > 1 > 0.85 High risk Waist to height ratio: may be a better predictor of CV, DM, and stroke risk, waist circumference should be less than ½ the height for healthy individual Good indicator of central adiposity Satiety: a feeling or condition of being full after food Amylin: pancreatic hormone that reduces pre-meal hunger Leptin: Hormone produced by adipocytes that inhibits food intake and causes satiety. Obese patients usually have leptin resistance. GLP-1: hormone that is produced by the small and large intestine in the presence of carbs, fiber, FFAs that decrease gastric emptying and promotes satiety. Usually decreased in obese patients. Peptide YY: Peptide produced by the large intestine and colon in the presence of fat, FFAs, carbs, protein, bile acid that decreases gastric emptying and next meal hunger. Usually decreased in obese patients. Adiponectin: a protein hormone produced and secreted exclusively by adipocytes that regulates the metabolism of lipids and glucose Gastric bypass: a surgical bypass operation performed to restrict food intake and reduce absorption of calories and nutrients in the treatment of severe obesity. Typically involves reducing the size of the stomach and reconnecting the smaller stomach to bypass the first portion of the small intestine Lap-Band surgery: Laparoscopic gastric band to make the stomach smaller, limiting the amount of food it can hold Metabolic syndrome: an interrelated group of medical abnormalities often present in patients who develop CVD or DM Relates to abdominal obesity, dyslipidemia, HTN, insulin resistance, inflammation, and prothrombotic state 32% of americans have MetS, more common in men and mexican americans MetS causes a 1.5-3 fold increase in risk of ASCVD and 3.5-5 fold increase in risk of T2DM Diagnosis AHA/NHLBI Any 3 of the following: IDF 2005 Central Obesity (male > 37 in and female > 31 in) Plus any 2 of the following: Increased waist circumference Men > 39 in Women > 35 in TG > 150 mg/dL TG > 150 mg/dL Men HDL < 40 Women HDL < 50 Men HDL < 40 Women HDL < 50 BP > 130/80 BP > 130/80 Glucose > 100 mg/dL Glucose > 100 mg/dL Pediatric MetS Criteria: greater than or equal to 90th percentile Over 16- same as the adult criteria Multiple CVD risk factors in patients with MetS: 50% with DM have HTN and HLD MetS can cause other diseases such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), polycystic ovarian syndrome (PCOS), and sleep apnea syndrome (SAS) Primary goal: reduce risk for clinical atherosclerotic disease and reduce risk for T2DM First line therapy: control major risk factors Exercise/weight loss Decrease BW by 7-10% in first year (goal BMI < 25) Waist < 40 in men and < 35 in women 30 minutes aerobic activity for over 5 days/week or 30-60 minutes every day with resistance training 2x/week Decrease intake of saturated sat (less than 7% total calories), trans fat, and cholesterol (< 200 mg/day) Control lipids, BP, glucose Tobacco cessation No current treatments aimed at MetS specifically, but can add low dose aspirin if the patient has either T2DM or ASCVD Syndrome X: a group of risk factors (glucose intolerance, high triglycerides, obesity, and hypertension) that indicate a predisposition to diabetes Body Mass Index (BMI) = weight (kg) / height (m2) Normal weight: 18.5-24.9 Overweight: 25-29.9 Class I obesity: 30-34.9 Class II obesity: 35-39.9 Class III obesity: > 40 Advantages: simple, increased BMI generally correlates well with fat mass and metabolic diseases, commonly used, reproducible, low cost, adequate screening tool Disadvantages: may not correlate for an individual patient, does not account for muscle mass or elderly with muscle loss, no distinguishment between men and women or between races Actual body weight (ABW) = total body weight (TBW) Percent Body Fat Advantages: more specific assessment of body fat, reasonable longitudinal measure for patient who are not losing weight but are exercising Disadvantages: not always accurate/reproducible, expensive, cut off points not validated for correlation to metabolic disease Ideal body weight (IBW) Lean body weight (LBW) Fat free mass (FFM) Body surface area (BSA) Predicted normal weight (PNW) Adjusted body weight (BWadj) Pathophysiology of Obesity: energy intake > energy expenditure = weight gain Poor satiety response = the body does not tell you to stop eating when it should Reasons for poor satiety response: food type (energy dense food such as high fat or refined sugars do not produce a strong satiety response), genetics (FTO gene, fat mass and obesity associated gene), GI peptide response (amylin, leptin, GLP-1, peptide YY), CNS response (5-HT, dopamine, NE, endocannabinoids, monoamines, GABA GI peptides involved in appetite control: they modify intestinal transit, change rules of nutrient absorption, stimulate vagal signals, and CNS CNS substances involved in appetite control: stimulate brain towards a satiety response and/or alter the food/reward system 5-HT: stimulation causes satiety (most likely through increase in leptin), receptors are 5-HT 2c and 5-HT 1b Dopamine: affects hunger and food/reward system, also involved in psychiatric side effects NE, monoamines: influence 5-HT levels. Involved in cardiovascular and psychological side effects Endocannabinoids: affect the food reward system via opioid receptors delta, kappa, mu and CB1 to affect desire for food and food enjoyment GABA: unclear role Adipocytes have adverse cardiometabolic effects (hypertension, T2DM, atherogenic dyslipidemia, thrombosis, atherosclerosis, and inflammation) IL-6: pro-atherogenic and pro-diabetic due to increase vascular inflammation and decreased insulin signaling, often elevated in obesity TNFa: pro-atherogenic and pro-diabetic due to decreased insulin sensitivity in adipocytes (paracrine), often elevated in obesity Adiponectin: anti-atherogenic and anti-diabetic, causes decreased foam cells, decreased vascular remodeling, decreased hepatic glucose output, and increased insulin sensitivity, often decreased in obesity Clinical manifestations of Fat Mass Disease Psychosocial, general biases, healthcare provider bias, weight bias internalization, negative self or external perceptions Obesity is a multifactorial disease: genetics/epigenetics, environment, immune, medical, endocrine, neurobehavioral Patient assessment of Obesity History Weight history, PMH, family history, social history, assess for drug induced weight gain, food intake, activity, review of systems Physical Exam Height, weight, bp, body composition analysis, waist measurement, complete physical examination Laboratory tests CBC, electrolytes, liver and kidney function, fasting lipid profile, thyroid tests, A1C, uric acid, vitamin D Diagnostic testing EKG, echocardiogram, exercise stress test, sleep study, barium swallow or esophagoduodenoscopy Risk Factors for obesity Women > Men Women have higher body fat composition due to less muscle mass Family History TFO gene, eating habits Age Decreased muscle mass in the elderly correlated to decreased metabolism (increased weight) Medical Conditions Hypothyroidism Cushing’s disease Mental disorders Medications Hormones Weight gain: glucocorticoids, estrogens Cardiovascular Weight gain: propranolol, atenolol, metoprolol, nifedipine (edema), amlodipine (edema), felodipine (edema) Diabetes Weight gain: insulin, sulfonylureas, thiazolidinediones, meglitinides Weight loss: metformin, GLP-1 RA, SGLT2i’s, alpha glucosidase inhibitors Anti-seizure Weight gain: carbamazepine, gabapentin, valproate Antipsychotics Weight gain: olanzapine Some weight gain: chlorpromazine, paliperidone, risperidone Variable/neutral: haloperidol Hypnotics Weight gain: diphenhydramine Sedentary lifestyle Energy intake > expenditure Nutrition Fat and refined sugars less effect on satiety Social/economic issues Cannot afford to make healthy dietary choices, lack proper resources for exercise Complications of obesity Neurologic: depression, anxiety Mechanical: incontinence, sleep apnea, asthma, osteoarthritis, impaired physical functioning (back pain, joint pain, etc) Metabolic: cardiovascular disease (stroke, dyslipidemia, HTN, CAD, VTE, HFpEF), non-alcoholic fatty liver disease, gallstones, type 2 diabetes, pre-diabetes, infertility, polycystic ovarian syndrome (PCOS), gout, malignancy Dosing challenges with obesity Clinical trials will often exclude obese patients If a dose is weight based, is it actual body weight or another measure? How much does the patient actually weigh? Cardiac output released to LBW Drug clearance is more closely related to LBW Volume of distribution could have several most accurate measures and depends of drug kinetics IBW is used in PK studies in the literature LBW changes as a function of weight, height, and sex LBW increases as weight increases Using BMI, IBW, or LBW to categorize obesity overestimates body fat in muscular patients and underestimates body fat in older patients or those with reduced muscle mass Obese = BMI > 25-30 or ABW/IBW > 1.2 Obesity Impact on Kinetics Variable Effect of Obesity Rationale Absorption None N/A Distribution Significant Changes in body composition affect Vd Lipophilicity of the drug = increased accumulation in fat tissue Metabolism Significant Fat accumulation in the liver decreases blood flow Glucuronidation and sulfation increase as ABW increases Effects can be variable (diazepam has increased clearance with obese patients and methylprednisolone has decreased clearance with obese patients) Excretion Significant Increased GFR of hydrophilic drugs due to changes in the volume of distribution Obese patients have increased total clearance and may respond less to the same amount of drug Dosing on mg/kg may cause toxicity because clearance does not proportionally increase with ABW, mg/kg per LBW may be more accurate Estimating ClCr in obese patients Muscular: use ABW Muscular with a belly: use LBW or ABW For couch potatoes: use LBW or IBW For emaciated: use ABW Benefits of treating obesity MNT and regular physical activity improves anatomic, physiologic, inflammatory, and metabolic body processes Medically managed weight reduction improves glucose and lipid metabolism, reduces BP, and reduces risk of thrombosis Weight loss in patients decreases obesity risk in children Weight loss reduces complications associated with obesity Treatment guidelines Physical activity: 150 minutes moderate physical activity/week Diet: any suitable eating pattern for the patient Behavioral therapy: twice monthly individual or group counseling for over 6 months Pharmacotherapy: BMI > 27 + comorbidity or BMI > 30 Surgery: BMI > 35 + comorbidity or BMI > 40 Current treatments Lifestyle intervention Healthy eating (medical nutrition therapy) Physical activity Behavioral activity Pharmacotherapy Phentermine (short term use only) Xenical (Orlistat) Qsymia (topiramate/phentermine) Contrave (naltrexone/bupropion) Saxenda (liraglutide 3 mg) Wegovy (semaglutide 2.4 mg) Devices Duodenal-jejunal bypass sleeve Intragastric balloon Vagal nerve blockade Cellulose-citric acid hydrogel capsule Transpyloric shuttle Surgery Biliopancreatic diversion Laparoscopic adjustable gastric banding Roux-en-Y gastric bypass Vertical sleeve gastrectomy Medical Nutrition Therapy Health outcomes are most improved if evidence based, quantitative, qualitative, and conducive to patient adherence Fat restricted diet (10-30% of total calories from fat) Low carbohydrate diet (50-150 g carbs/day) Very low carbohydrate diet (under 50 g carbs/day) Ultra Processed carbohydrates and saturated fats increase ASCVD risk Each person has a specific amount of calories required to maintain/lose/gain weight Sodas and sports drinks increase obesity as well as foods “Dos”: consume a healthy eating pattern within an appropriate calorie level, vegetables, fruits, whole grains, fat-free or low fat dairy, variety of proteins “Don’ts”: consume > 10% calories from added sugar or saturated fats, consume over 2.3 g of sodium per day, alcohol Diet Information Pros Cons Ketogenic Low carb Decreased UPCs, glycemic index, trans fats Decreased postprandial glucose and insulin, decreased BP, decreased TG, increased HDL Adherence Increased LDL Fatigue Mediterranean Olive oil Increased veggies, fruits, legumes, whole grains, nuts, seeds Decreased UPCs and red meat Decrease ASCVD High in unsaturated fat Safe in kids Adherence Weight loss may be less than low carb DASH Increased veggies, fruits, legumes, whole grains, nuts, seeds, low fat dairy, poultry, lean meats Decreased UPCs, sodium, saturated fats, red meats Decrease ASCVD Decrease BP Decreased lipids Adherence Weight loss may be less than with low carb Vegetarian Increased veggies, fruits, legumes, whole grains, nuts, seeds, low fat dairy Decreased ASCVD Anti-inflammatory Adherence Unhealthy options that are still vegetarian Fasting Periodic: Limit food for 2 days, then eat normal for 1 week Intermittent: limit food intake on certain days Time restricted feeding: food limited to a fixed time or day Improved BP, HR, HDL, LDL, TC, TG, glucose and insulin resistance Decreased inflammation and oxidative stress from atherosclerosis Adherence Does not emphasize healthy foods Increased hypoglycemia risk in DM patients Diets and Medication interactions Consider medications that need to be taken with food (rivaroxaban and zisperidone) or on an empty stomach (levothyroxine and bisphosphonates) Variations in protein, dairy, fruit and vegetable content Increased albumin (phenytoin, amiodarone) Antibiotics and milk/cheese/yogurt Grapefruit and CYP interactions Vitamin K and warfarin Alterations in gut flora Side effects (nausea, diarrhea, vomiting, constipation) Behavioral Counseling for Obesity Screening using BMI Nutritional assessment Intensive behavioral counseling and therapy Includes: Month 1: 1 face-to-face visit/week Month 2-6: 1 face-to-face visit every 2 weeks Month 6: reassessment Additional visits reserved for patients who lost > 3 kg Patients who did not lose > 3 kg can reapply in 6 months Month 7-12: 1 face-to-face visit/month 5 A’s of obesity management Ask: permission to discuss body weight, explore readiness for change Assess: assess BMI, wait circumference, obesity stage, explore drivers and complications of excess weight Advise: health risks, benefits of weight loss, need for long-term treatment strategy, treatment options Agree: realistic expectations, targets, behavioral changes, specific details Arrange/assist: barriers, resources, appropriate providers, arrange regular follow up Physical Activity: Assessing mobility Unable to walk: seated exercise program, arm exercises, swimming, aquatic exercises, gravity mediated PT, consider physical therapy evaluation Limited mobility, able to walk: walking, swimming, aquatic exercises, gravity mediated physical activity, assess for special equipment needs No limitations: driven by patient and guided by clinician, assess need for special equipment Physical activity goals Resistance training 2 times/week Minimum 5000 steps per day and/or 150-300 minutes moderate intensity aerobic activity or 75-100 minutes of more vigorous training per week Leisure time physical activity: competitive or non-competitive sports Transportational/Occupational Non-exercise Activity Thermogenesis (NEAT): walking instead of taking transportation, taking the stairs, carrying overnight bags, active work environment, avoid prolonged inactivity Exercise Examples Light: walking around the home, arts and crafts, playing musical instrument, playing darts Moderate: power walking, danging, bicycling, tennis doubles Rigourous: walking, running, jogging, shoveling snow, swimming, basketball game MET = metabolic equivalent, represents an average person’s resting metabolism or oxygen uptake Women: 14.7-(0.13*age in years) Men: 14.7-(0.11* age in years) Anti-Obesity Medications Phentermine: sympathomimetic amine, contraindicated in ASCVD patients Suprenza, Lomaira, Adipex-P Use over 12 weeks is contraindicated Target: CNS MOA: amphetamine, causes release of norepinephrine and epinephrine Anorexiant, weight loss Orlistat: GI lipase inhibitor with some efficacy but side effects that include oily rectal discharge, fecal urgency, defecation, and flatulence Alli, Xenical Take TID with high fat meals Target: GI tract MOA: reversible inhibitor of intestinal lipase, unable to absorb any triglycerides Inhibits fat-soluble vitamin absorption (ADEK) so supplementation is necessary 120 mg Rx or 60 mg OTC, TID Lorcaserin: 5-HT 2c agonist, voluntarily withdrawn from the market due to increase in pancreatic cancer Liraglutide: GLP-1 receptor agonist, 3 mg daily for obesity with possible GI side effects Saxenda Target: CNS and periphery MOA: agonist for GLP-1 receptor Maintained blood glucose and weight Contraindicated inpatients with family history or history of thyroid CA Can be taken with or without meals, expensive, once weekly injection No renal dose adjustment Side effects: nausea, vomiting, increased HR Semaglutide Wegovy Target: CNS and periphery MOA: agonist for GLP-1 receptor Maintained blood glucose and weight Side effects: nausea, vomiting, diarrhea, constipation, abdominal pain, thyroid cancer risk Once weekly injection, no dose adjustments, expensive Tizepatide Mounjaro Target: CNS and periphery MOA: agonist at GLP-1 receptor Maintained blood glucose and weight Side effects: nausea, vomiting, diarrhea, thyroid cancer risk Once weekly injection, no dose adjustments needed, expensive Not currently FDA approved for weight loss Naltrexone/bupropion: opioid antagonist/antidepressant with GI side effects Contrave Target: CNS MOA: opioid receptor antagonist, norepinephrine and epinephrine reuptake inhibitor Reduced appetite and weight loss Contraindicated with uncontrolled HTN, chronic opioid use, seizures, abrupt d/c of alcohol, benzodiazepines, barbiturates, and AEDs Side effects: nausea, HA, constipation, dizziness, vomiting Lack of ASCVD benefit Dosing: 16/360 mg BID or 32/360 mg BID Should not be taken with high fat meals due to increased absorption Phentermine/topiramate: sympathomimetic/anti-seizure/migraine with side effects including paresthesias and dysgeusia Qsymia Target: CNS MOA: modulation of GABA, inhibition of carbonic anhydrase and glutamate. Topiramate causes decreased leptin Side effects: constipation, diarrhea, HA, paresthesias, tachycardia Appetite suppression Contraindicated in pregnancy and with MOAIs Dose reduce in liver impairment Can be taken with/without meals once daily, but is incredibly expensive None of the herbal medications for weight loss have been shown to be safe or effective in clinical trials, common cause of hepatotoxicity Chromium picolinate = chromium St. John’s wort = hypericin Hoodia = P57 White willow bark = salicylate Guarana extract, tea extracts = caffeine Garcinia gambogia extract (citrin) = hydroxycitric acid Chitosan = cationic polysaccharide Obesity Drug List Pros and Cons Drug Pros Cons Phentermine Inexpensive 3-5% weight loss Side effects No long term use Topiramate/phentermine > 5% weight loss Long term data Expensive CI in pregnancy Orlistat (Rx) Non-systemic Long-term data 2-3% weight loss Side effect profile Orlistat (OTC) Inexpensive 2-3% weight loss Side effect profile Naltrexone/bupropion 3-5% weight loss Food addiction Long-term data Side effects Mid-level price range GLP-1 RAs More weight loss than other agents Side effects Long-term data Expensive Injectable Obesity Management: Devices Plenity- superabsorbent hydrogel capsules taken with water before lunch and dinner MOA: particles rapidly absorb water in the stomach, creating a gel matrix to increase the volume and elasticity of the stomach and small intestine contents, feel full and induce weight loss Contraindicated in pregnancy or allergies Caution in patients with GERD, ulcers, or heartburn May alter the absorption of some medications Gastric balloons- inflatable balloons placed in the stomach to take up space Indications: weight reduction in combination with diet and exercise, BMI 30-40 + comorbidity, not a first line treatment Contraindicated with GI diseases Side effects: GI Metabolic and Bariatric Surgery Indicated in patients BMI > 40 or BMI > 35 + HTN, T2DM, or sleep apnea Part of a comprehensive plan May cause remission of chronic diseases and allow for discontinuation of medications Older procedures had high failure rates and dangerous complications Procedure Pros Cons Expected weight loss Optimal for Other comments Roux-en-Y gastric bypass Greater improvement in metabolic disease Increased risk of malabsorptive complications over sleeve 60-75% Patients with high BMI, GERD, T2DM Largest data set, more technically challenging Vertical sleeve gastronomy Improves metabolic disease, maintains small intestine anatomy, micronutrient deficiency is infrequent No long term data 50-70% Metabolic disease Can be used as the first step of a staged approach Laparoscopic adjustable gastric banding Least invasive, removable 25-40% removal rate 30-50% Lower BMI, no metabolic disease Any metabolic benefits achieved are dependent of weight loss Biliopancreatic Diversion with duodenal switch Greatest amount of weight loss and resolution of metabolic disease Increased risk of nutrient deficiencies 70-80% Higher BMI, T2DM Most technically challenging Gastric Bypass 50-75% loss in excess weight Dumping syndrome: occurs when patient eats calorie rich food, nausea, vomiting, diarrhea, SOB 0.5% mortality Lap Band 48% excess weight loss Improvement in HTN, HLD, DM and sleep apnea Heartburn or bleeding due to bandage slipping Infection bleeding (1%) mortality (0.1%) Bariatric Surgery Common Micronutrient Deficiencies RNY: B1, B9, B12, D, Ca, Fe Sleeve: B1, B9, B12, D, Fe LAGB: B1, D BPD: A, B1, B9, B12, D, E, K, Ca, Fe, Zn Bariatric Surgery Medication Considerations Absorption affected based on type of procedure Malabsorption concern with narrow therapeutic window drugs Increase in gastric pH (can be bad for drugs that require low pH like rifampin, digoxin, and iron) Change medications to liquid, openable, crushable forms and consider size of tablet Avoid medications that increase risk of gastric bleed (NSAIDs + bismuth) Pulmonary Hypertension- Dr. Devlin (6/21) What can cause pressure in the pulmonary artery to increase? Changes in the blood vessels What can cause pressure in the pulmonary vein to increase? Changes in the heart Pulmonary arterial hypertension: high blood pressure in the lungs Mean PAP (pulmonary artery pressure) at rest > 25 mmHg Often leads to right sided heart failure Median survival rate after diagnosis without treatment = 2.8 years Constriction of the pulmonary arteries and an enlarged right ventricle occur as a result of pulmonary hypertension The narrowing of pulmonary arteries can be due to vascular remodeling and fibrosis or thrombosis Pre-symptomatic/Compensated: Cardiac output is maintained and PAP and PVR are low Symptomatic/Decompensating: Cardiac output starts to fall as the patient crosses the symptom threshold. PAP and PVR begin to rise. Declining/Decompensated: Cardiac output falls (right heart dysfunction) and PAP starts to fall as well. PVR remains high. WHO-E Group 1: idiopathic or associated Idiopathic (cannot determine the reason for PAH) Associated Pulmonary Arterial Hypertension (APAH): collagen vascular disease (lupus), portal hypertension secondary to liver failure, HIV infection, drugs/toxins (stimulants, diet pills, PPA) WHO-E Group 2: left heart failure Systolic dysfunction, diastolic dysfunction, valvular disease Most common cause of PAH! WHO-E Group 3: lung disease or chronic hypoxemia COPD, interstitial lung disease (ILD), obstructive sleep apnea (ONA), chronic exposure to high altitudes WHO-E Group 4: chronic thromboembolic pulmonary hypertension Chronic thromboembolic disease that obstructs the pulmonary arteries Pulmonary embolism WHO-E Group 5: unclear/multifactorial causes Symptoms of PAH: dizziness or fainting (syncope), shortness of breath (dyspnea), chest pain (angina), swollen ankles and legs (edema), fatigue WHO PAH Functional Class aka WHO-F Class Symptoms F-I No dyspnea/fatigue present at rest or with usual physical activity (walking up a short flight of stairs) F-II No dyspnea/fatigue present at rest but one or both present with usual physical activity (walking up a short flight of stairs) F-III No dyspnea or fatigue at rest but one or both present with simple activities of daily living (walking to the bathroom) F-IV Dyspnea and/or fatigue at rest; nearly impossible to do activities of daily living Right Heart Catheterization Diagnostic Gold Standard Cardiac index Pulmonary Capillary wedge pressure > 15 means left sided heart failure is unlikely Mean pulmonary artery pressure (MPAP) Vasodilator testing 6 minute walk test (6MWT) Measures patient’s functional capacity and correlates well with quality of life measurements Do not do this test in patients with an MI in the past month or active cardiac ischemia 100 ft hallway- patient can use oxygen if the utilize it at home, Cash cart and MD