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Block 9: Cardio, Renal and Resp II > Week 3 (Hypertension, Hypertrophy and Heart Failure) > Flashcards

Week 3 (Hypertension, Hypertrophy and Heart Failure) Flashcards

1
Q

Mechanisms of regulation of blood pressure

A

Renal

Hormonal

Neural

Vascular

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2
Q

Initial evaluation of patient with hypertension

A

1) Accurately stage BP
2) Assess overall cardiovascular risk
3) Seek clues for rare secondary causes

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3
Q

Staging BP

A

Normal: <120/80

Prehypertension: <140/90 (2x as likely to progress to HTN, but not known if treating this helps morbidity/mortality)

Stage 1 hypertension: <160/100

Stage 2 hypertension: >160/100

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4
Q

When do you take additional BP measurements?

A

Take 2nd measurement if clinic BP >140/90

Take 3rd measurement if BPs differ

Record lower of last 2 as clinic BP

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5
Q

White coat reaction

A

White coat (office-only) HTN: BP is only high in doctor’s office but otherwise completely normal in daily life

White coat aggravation: BP higher in doctor’s office but still not normal in daily life (alerting reaction superimposed on fixed HTN)

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6
Q

Masked HTN

A

BP is only normal in doctor’s office, masking the diagnosis of hypertension

This happens if stress of daily life (but more relaxed in doctor’s office)

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7
Q

Normative cutoff values for 24 hour ambulatory BP monitor

A

Awake average: <135/85

24 hour average: <130/80

Sleep BP: <120/70

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8
Q

Home BP measurement

A

Measure BP in AM and PM daily x 7 days (though 4 is probably fine)

Discard first day’s BPs and average all the rest

Normative cutoff value <135/85

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9
Q

Isolated systolic hypertension

A

Systolic >140

Diastolic <90 (normal)

This is the kind of HTN people over 50 have

Primary fault is decreased distensibility of large arteries (aorta stiff) because collagen replaces elastin in elastic lamina of aorta, which is age-dependent process accelerated by atherosclerosis and HTN

Cardiovascular risk here is related to pulsatility, repetitive pounding of blood vessels with each cardiac cycle and more rapid return of arterial pulse wave from periphery, both causing more systolic HTN

Higher risk for fatal MI than combined sys/diast HTN

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10
Q

Overall cardiovascular risk of HTN

A

Severity of HTN

Target organ damage from HTN

Other CV risk factors (age, family hx premature heart disease, dyslipidemia, DM, CKD, cigarette smoking, obesity, physical inactivity, dietary sodium)

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11
Q

HTN target organ disease

A

Neuro: stroke, TIA, dementia, retinopathy

Cardiac: atrial fibrilation, heart failure

Renal: CKD

Vascular: angina, MI, coronary revascularization, aortic aneurysm, peripheral vascular disease (PVD)

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12
Q

Hypertension physical exam

A

Neurologic exam

Fundoscopy

Neck: palpation and auscultation of carotids, thyroid

Lungs: rhonchi, rales

Heart: size, rhythm, sounds

Accurate BP measurement

Abdomen: renal masses, bruits over aorta or renal arteries, femoral pulses

Extremities: peripheral pulses, edema

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13
Q

Hypertension standard labs

A

Blood chemistries: electrolytes, serum creatinine, glucose, lipid profile

Spot urinalysis: albumin

ECG: left ventricular hypertrophy (uncontrolled HTN), atrial fib, coronary disease

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14
Q

Hypertensive emergency vs. urgency

A

Both are BP >160/100

Hypertensive urgency: stable or no target organ damage –> give oral Rx in ER and clinic appt 72h later

Hypertensive emergency: rapidly progressive target organ damage (aortic dissection, post-CABG hypertension, acute MI, unstable angina, eclampsia, head trauma, body burns, postop bleeding from vascular suture lines) –> parenteral Rx, admit to ICU for hemodynamic monitoring and IV therapy

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15
Q

Multi-factorial causes of primary HTN

A

Genetics: cell membrane alteration

Obesity: insulin

Endothelial factors: structural changes effect RAAS

Stress: activation of SNS

Diet: sodium retention causes increased fluid volume

Kidney disease: sodium retention causes increased fluid volume

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16
Q

Treatment of primary vs. secondary HTN

A

Primary HTN can be managed with medication but not cured

Secondary HTN, if diagnosed, can lead to definitive cure

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17
Q

Secondary HTN

A

RAAS:

CKD: elevated serum creatinine or abnormal UA

Renovascular HTN: elevated serum creatinine (esp after ACEI or ARB), refractory HTN, flash pulmonary edema, abdominal bruit

Coarctation of aorta: arm pulses > leg pulses, arm BP > leg BP, chest bruits, rib notching on CXR

Primary hyperaldosteronism: hypokalemia, refractory HTN

Other mineralcorticoid excess (Cushing’s where cortisol stim aldosterone receptor): truncal obesity, purple striae, muscle weakness

NSAIDs: block renal prostaglandins, causing salt-dependent HTN in some patients

SNS:

Pheochromocytoma: spells of tachycardia, headache, diaphoresis, pallor and anxiety = paroxysmal HTN, pain in the head, palpitations, pallor, perspiration (check metanephrine and normetanephrine, adrenal CT)

OSA: loud snoring, daytime somnolence, obesity (do sleep study)

Other: sympathomimetics, cyclosporine A, baroreflex failure, thyroid disease

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18
Q

Combined systolic and diastolic hypertension

A

Both systolic and diastolic BP elevated (>140/90)

More common in those under age 50

Main fault is vasoconstriction at level of resistance arterioles

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19
Q

Hypertension in African Americans

A

HTN more common in AAs (1/3 compared to 1/4 or 1/5 in whites/Mexicans), even those with access to healthcare

This is definitely a problem of environment since Africans in Africa do not have increased rates of HTN (remember salt-retention theory of slaves coming to US from Africa)

Starts at a younger age

More severe

More target organ damage

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20
Q

High-risk hypertensive patients

A

Diabetes

CKD

Established CAD (secondary prevention)

Atherosclerotic disease of other arteries: carotids (bruits), abdominals (aneurysm), peripheral artery disease (PAD)

High risk for CAD (primary prevention)

Heart failure

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21
Q

What do diuretics do?

A

Diuretics increase renal Na+ excretion (“natriuresis”) which leads to negative Na+ balance

Patients have natriuresis (excretion of salt) for about a week, then get to new steady state where Na input = Na output, but this is at a lower body volume (weight) than before diuretic

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22
Q

Factors that limit natriuresis and counteract diuretic induced volume depletion

A

Increase AT II and NE stimulates proimal Na+ reabsorption and passive H2O reabsorption

Increase aldosterone which increases collecting duct Na+ reabsorption

Increase ADH stimulates H2O reabsorption at collecting tubule

Counter-regulatory responses limit Na+ wasting induced by fixed diuretic does

All net Na+ losses occur within the first week on fixed dose of diuretic and dietary salt intake

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23
Q

Carbonic anhydrase inhibitors

A

Acetazolamide

Absorbed orally, excreted by kidney

Acts on PCT to inhibit NaHCO3 reabsorption (so you excrete more HCO3)

Mimics RTA type 2 because inhibits reabsorption of HCO3

By increasing distal Na+ and HCO3- delivery, K+ secretion increased –> hypokalemia

CA inhibitors are “weak” diuretics because Na+ absorption occurs along more distal portions of nephron to “pick up the slack”

Specific uses of CA inhibitors: refractory metabolic alkalosis esp if volume overload and CO2 retention needs to be avoided (because furosemide alone worsens metabolic alkalosis but CA inhibitor induces metabolic acidosis), prophylaxis/tx of high altitude sickness, alkalinization of urine, glaucoma

Don’t give if GFR <10 or liver failure (disruption of urea cycle) or metabolic acidosis (because not much HCO3 filtered, so won’t work well)

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24
Q

Loop diuretics

A

Bumetanide, furosemide (short-acting), torsemide (long-acting), ethacrynic acid

Block Na/K/2Cl co-transporter in TALH

Used in edematous states (CHF, cirrhosis, nephrotic syndrome), HTN (esp in setting of CKD or high Na+ retention states), relative hypervolemic hyponatremia (because can’t reabsorb water), SIADH hyponatremia, hypercalcemia (prevents reabsorption of Ca2+!)

Increased distal delivery of Na+ –> hypokalemia and metabolic alkalosis

Reduced NaCl reabsorption in TALH leads to reduction in medullary tonicity –> suboptimal free water reabsorption at collecting duct

Adverse effects: volume depletion, volume depletion-mediated AKI (esp with ACEI, ARB, NSAIDs), hypokalemia, hypomagnesemia, metabolic alkalosis, ototoxicity, glucose intolerance with hypokalemia (because need K+ in order to allow insulin to bring glucose into cells)

Excreted in kidney via organic anion transporter into lumen

Effective with reduced GFR

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25
Q

Why are loop diuretics so effective?

A

Block reabsorption of large portion of Na+ delivered to TALH

Reduced medullary tonicity leads to lower H2O reabsorption at collecting duct

No high capacity distal segments to compensate for increased Na+ delivery

Work even at reduced GFR

Disrupt tubuloglomerular feedback so GFR maintained despite increased distal delivery of Cl- to macula densa (which would usually reduce renin to reduce renal perfusion)

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26
Q

Thiazide diuretics

A

Hydrochlorothiazide (common, short-acting, not good at low GFR), chlorthalidone (long acting, not good at low GFR), metolazone (lasts 24h, works at lower GFR, used with loop diuretic)

Block Na/Cl cotransporter in DCT

Used in HTN, mild edematous states, hypercalciuric stone disease (increases reabsorption of Ca2+!), nephrogenic DI (can reabsorb water because medullary tonicity not changed)

Adverse effects: increased K+ excretion –> hypokalemia, risk for hyponatremia (esp old malnourished women; because reabsorb too much water), reduced uric acid excretion –> gout, reduced Ca2+ excretion (hypercalcemia), reduced islet cell insulin secretion due to hypokalemia, hypomagnesia, hyperlipidemia

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27
Q

K+ sparing diuretics

A

Spironolactone: non-selective aldosterone blocker (blocks apical ENaC and basolateral Na/K ATPase); 20 hour half life, gynecomastia, metrorrhagia, preferred in high aldo states

Eplerenone: selective aldosterone antagonist (blocks apical ENaC and basolateral Na/K ATPase); 4-6 hour half life, no gynecomastia

Amiloride: ENaC blocker, 6-9 hour half life, renally excreted

Triamterene: ENaC blocker, 3-5 hour half life, accumulates in kidney and liver failure, may form triamterene stones

Clinical uses: in combination with K+ wasting diuretics (NCTZ + triamterene in essential HTN, furosemide + spironolactone for cirrhosis), amiloride for Liddle’s syndrome (gain of fxn mutation of ENaC), spironolactone for hyperaldosteronism, cirrhosis and CHF

Adverse effects: volume depletion (hypotension, AKI/ATN, high BUN/Cr), electrolyte abnormalities (altered mental status, arrhythmias), allergic reactions, AIN, hyperkalemia and metabolic acidosis?

Don’t use in patients with kidney disease or hyperkalemia because could cause hyperkalemia bad enough to cause arrhythmias

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28
Q

Mannitol

A

Osmotic diuretic

Increases intravascular volume, hence GFR and renal excretion of salt and water, used to reduce brain edema/ICP

Possible problems: acute intravascular volume expansion, pulmonary edema (esp if poor kidney function/urine output since pulls fluid into intravascular space), dehydration and hypernatremia (water loss > Na+ loss)

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29
Q

What factors determine potency of diuretics

A

Bioavailability and dose

Quantity of Na+ delivered at site of action

Ability of more distal nephron segments to reabsorb excess Na+

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30
Q

2 systems of RAAS

A

Circulating endocrine system: acute effect, maintenance of BP, peripheral organ perfusion, prevention of hemodynamic collapse

Tissue system (autocrine and paracrine): long term control of BP, organ growth and function

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31
Q

Summary of RAAS

A

1) Angiotensinogen made by liver
2) Renin from JGA cells of afferent arteriole (?) converts angiotensinogen to angiotensin I
3) ACE from lungs (and neuroepithelium, plasma and vascular endothelium), etc converts ATI to ATII
4) ATII acts on AT1 receptor (hypertrophy/proliferation, vasoconstriction, thrombosis/fibrosis, aldosterone, vasopressin) and AT2 receptor (antiproliferation, antifibrosis, vasdilation, apoptosis)

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32
Q

Actions of aldosterone

A

Na+ absorption causes fluid retention, potentiates HTN

K+ and Mg2+ loss causes arrhythmias

Profibrinogenic effect causes myocardial fibrosis, thrombogenesis, vascular inflammation, endothelial dysfunction

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33
Q

Summary of kallikrein-kinin system

A

1) Kininogen converted to lysyl-bradykinin by kallikrein
2) Lysyl-bradykinin converted to bradykinin by aminopeptidase
3) Bradykinin degraded to inactive peptides by ACE (kininase II)

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34
Q

What does bradykinin do?

A

Overall: reduce BP, cause pain and redness

Mediates vasodilation (stimulates NO formation)

Prostaglandin formation

Enhanced vascular permeability

Inhibition of renal sodium and water reabsorption (natriuresis)

Nociception

Contraction of visceral smooth muscle

Release of inflammatory mediators

Stimulation of sensory nerves

Release of NO, PGI2, t-PA

Note: aloe vera has anti-bradykinin effects, which is why you put it on red cuts

Note: ACE inactivates bradykinin (usually does vasodilation) and activates ATII (does vasoconstriction) which have similar effects on BP!

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35
Q

Indications for ACE inhibitors

A

Hypertension

CHF (EF <40%)

Acute MI

Mitral regurg

Aortic regurg

Slowing progression of CKD (both diabetic and non-diabetic)

Proteinuria

Secondary stroke prevention

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36
Q

What happens if AT1 receptor is stimulated too much?

A

Brain and vessels: atherosclerosis, vasoconstriction, vascular hypertrophy, endothelial dysfunction

Heart: LV hypertrophy, fibrosis, remodeling, apoptosis

Kidneys: glomerular hyperfiltration, increased proteinuria, increased aldosterone release, glomerulosclerosis

These things lead to stroke, HTN, HF, MI, renal failure which are all related!

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37
Q

Vicious cycle of neurohormonal activation in myocardial injury

A

1) Myocardial dysfunction/failure
2) Decreased CO and arterial pressure
3) Compensatory responses (RAAS, vasopressin)
4) SVR increases (afterload), blood volume and venoconstriction increases (preload)
5) These things cause further myocardial dysfunction/failure

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38
Q

Cycle of neurohormonal activation in kidney injury

A

1) Kidney injury
2) Decreased GFR
3) Compensatory responses (increased RAAS)
4) Improvement in GFR, remodeling of injured tissue, tissue proliferation, fibrosis

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39
Q

Adverse effects of ACEIs

A

Hypotension

Hyperkalemia

Increased serum creatinine (renal failure in some cases)

Coughs (Asians)

Angioedema (Blacks)

Fetal morbidity/mortality (neonatal skull hypoplasia, renal failure, ASD/VSD)

Rash

Neutropenia

Liver failure

Proteinuria (captopril, due to sulfa group)

Taste disturbances

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40
Q

ACEI induced cough

A

In 5-35%

More common in women, nonsmokers, Chinese

Etiology unclear but bradykinin stimulates NO and/or PG production; ACE gene polymorphisms, neurokinin 2 receptor gene polymorphisms

Treatment: d/c ACEI and coughs will resolve within 1-4 wks, but may be up to 3 months; can consider restarting ACEI

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41
Q

Contraindications for ACEI

A

Intolerance

Hypotension

Volume depletion

Pregnancy

Hyperkalemia

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42
Q

Which ACEIs are active and which are prodrugs?

A

All are prodrugs except captopril and lisinopril which are active

Can use active drugs in people with hepatic congestion (since prodrugs must be activated by liver)

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43
Q

How to use ACEIs

A

Start at low dose esp in hemodynamically tenuous patients

Use with precaution in CKD, RA stenosis, severe aortic stenosis (decrease afterload but if AS, can have hypotension), concomitant aggressive diuresis, existing increased serum K+, concomitant use with K+ sparing diuretics, ARB, NSAIDs

Monitor serum Cr, [K+] within 7-10 days

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44
Q

Why don’t you want to use NSAIDs and ACEI/ARB together?

A

NSAIDs constrict afferent

ACEI/ARB dilate efferent

Together this causes severe reduction in renal perfusion/filtration pressure which worsens glomerular filtration –> “pre-renal state” –> ATN (muddy brown casts)

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45
Q

What other substances can convert ATI to ATII?

A

Chymostatin-sensitive angiotensin II-generating enzyme (CAGE)

Cathepsin G

Chymase

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46
Q

What substances can turn angiotensinogen directly to ATII?

A

t-PA

Cathepsin G

Tonin

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47
Q

Angiotensin II receptor blockers (ARBs)

A

Candesartan (Atacand)

Eprosartan (Tevetan)

Irbesartan (Avapro)

Losartan (Cozaar)

Olmesartan (Benicar, Olmetec)

Valsartan (Diovan)

Telmisartan (Micardis)

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48
Q

Indications for ARBs

A

Similar to ACEI, can be used if intolerant of ACEI (coughs)

In patients with angioedema on ACEI, use ARB with extreme caution, if at all

Mild-moderate hyperkalemia with ACEI

Note: when you use ACEI, block both AT1 and AT2 effects, but with ARB, only block “bad” effects (hypertrophy/proliferation, thrombosis/fibrosis, vasoconstriction, aldosterone release, vasopressin) and keep the good effects (antiproliferation, antifibrosis, apoptosis, vasodilation)

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49
Q

Indications for aldosterone antagonists

A

Primary hyperaldosteronism

Diuretic (cirrhosis, CHF, nephrotic syndrome)

Advanced heart failure with ACEI and diuretics

Recent or current CHF symptoms despite ACEI, diuretics, digoxin, beta-blockers

Essential HTN

Slow progression of renal disease, DM with microalbuminuria

Congenital conditions with hypokalemia

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50
Q

Adverse effects of aldosterone antagonists

A

Hyperkalemia (esp in combination with ACEI/ARB, DM with microalbuminuria, renal insufficiency)

Gynecomastia, mastodynia, ED, abnormal vaginal bleed (spironolactone)

Agranulocytosis (spironolactone)

Cholestatic/hepatocellular toxicity

Gastritis, ulcerations, N/V, cramping, diarrhea

Rash

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51
Q

Direct renin inhibitors (DRI)

A

Potent competitive inhibitor of renin

Reduced LVH and renal protection in DM with proteinuria (in animal studies)

Antihypertensive, additive with ACEI/ARB, possibly long-term effect on end-organ protection, proteinuria (human trials)

Side effects: diarrhea with high doses, hyperkalemia

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52
Q

Actions of renin and pro-renin

A

ATII-dependent pathway: enzymatic activation of prorenin and increase of catalytic activity of renin –> increased angiotensin generation on cell surface –> organ damage

ATII-independent pathway: activation of intracellular signaling cascade, production of TGF-b1, PAI-1, collagen –> potential profibrotic and proliferative effects –> organ damage

Note: pro-renin can act independent of ATII

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53
Q

Stages of heart failure

A

Stage A: high risk for developing HF but no structural heart disease, no symptoms; pt has HTN, CAD, DM, fam hx cardiomyopathy

Stage B: asymptomatic HF; pt has previous MI, LV systolic dysfunction (structural heart disease), asymptomatic valvular disease

Stage C: symptomatic HF; pt has known structural heart disease, SOB and fatigue, reduced exercise tolerance

Stage D: refractory end-stage HF; pt has marked symptoms at rest despite maximal medical therapy, is recurrently hospitalized or cannot be safely discharged from hospital without specialized interventions, palliative care

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54
Q

Common and uncommon etiologies of HF

A

Common: CAD, atherosclerotic heart disease, hypertensive heart disease, idiopathic dilated cardiomyopathy, valvular heart disease (calcific aortic stenosis, mitral regurg, rheumatic heart disease), drugs (alcohol, cocaine, meth), HF with preserved ejection fraction (diastolic dysfunction)

Uncommon: congenital heart disease (ASD), infiltrative cardiomyopathy (amyloid, sarcoid, restrictive), hemochromatosis, thyroid disease, pheochromocytoma, CKD, HIV and viral cardiomyopathy

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55
Q

Symptoms of heart failure

A

Left atrial pressure (caused by elevated LV pressure): dyspnea, orthopnea, PND

Cardiac output: fatigue, decreased exercise tolerance

Right atrial pressure (systemic congestion on basis of elevated LV pressure): weight gain, edema, hepatic congestion

56
Q

Heart failure with reduced LVEF (systolic) vs. preserved LVEF (diastolic dysfunction)

A

Reduced LVEF: caused by CAD/HTN, may have dyspnea/fatigue, decreased CO, increased LV diastolic pressure, depressed LVEF

Preserved LVEF: caused by CAD/HTN, may have dyspnea/fatigue, decreased or normal CO, increased LV diastolic pressure, normal or increased LVEF

Need to measure EF to distinguish the two because they present very similarly

Treatment for reduced LVEF, but not for preserved LVEF!

57
Q

Prognosis of heart failure

A

Overall 50% 5-year mortality

Hospitalized patients 1-year mortality: mild to moderate symptoms have 10-20% mortality; severe symptoms have 40-60% mortality

Really bad, called “cancer of the heart” to communicate severity to pts

58
Q

Adverse effects common to all diuretics

A

Volume depletion: body response is increased proximal tubular reabsorption (Na, water, Ca2+, uric acid, urea) stimulation of RAAS, SNS, ADH; adverse outcomes are hypotension, AKI/ATN, high BUN:Creatinine

Electrolyte abnormalities: Na+, K+, Ca2+, Mg2+, altered mental status, hyponatremia, arrhythmias (K+, Ca2+, Mg2+)

Allergic reactions

AIN

59
Q

Furosemide vs. Thiazides and hyponatremia

A

When you use any diuretic, cause volume depleted state and crank up ADH

Furosemide: lose concentration gradient in medulla so cannot reabsorb a lot of water in the collecting duct (even though ADH still around) –> lose water and treat hyponatremia

Thiazides: normal concentration gradient in medulla so can reabsorb water in collecting duct (because of ADH secreted due to volume depletion) –> causes hyponatremia because lose Na+ > water

60
Q

Which ACEIs to use in renal insufficiency?

A

Benazepril and Fosinopril are hepatically excreted, so can be used in people with renal insufficiency

61
Q

Pathophysiologic effects of ATII and Epi/NE

A

Cardiac myocyte: hypertrophy, apoptosis, cell sliding, increased wall stress, increased O2 consumption, impaired relaxation

Fibroblast: hyperplasia, collagen synthesis, fibrosis

Peripheral artery: vasoconstriction, endothelial dysfunction, hypertrophy, decreased compliance

Coronary artery: vasoconstriction, endothelial dysfunction, atherosclerosis, restenosis, thrombosis

62
Q

Management of Stage C HF (ACC/AHA guidelines)

A

Life prolonging therapy

ACEI or ARB (both isn’t any better), beta blockers in all patients without contraindications or intolerance

Aldosterone antagonists in patients with mild, moderate, severe sx without contraindications or tolerance, when close monitoring can be assured

63
Q

ACEI/ARB use in HF

A

Indicated for all pts with asymtomatic LV dysfunction and Class I to IV heart failure

Contraindications: hyperkalemia, angioedema, pregnancy

Titrate to target dose

Monitor serum [K+] and renal function

Check chem panel 1-2 weeks after first dose

If ACEI not tolerated, recommend ARB (don’t use both together)

64
Q

Effects of aldosterone

A

Cardiac myocyte: hypertrophy, NE release

Fibroblast: hyperplasia, collagen synthesis, fibrosis

Peripheral artery: vasoconstriction, endothelial dysfunction, hypertrophy, decreased compliance

Kidney: K+ loss, Na+ retention

65
Q

Aldosterone antagonist use in HF

A

Indicated for pts with mild, moderate or severe HF due to LVD (LVEF <0.4)

Contraindications: hyperkalemia, Cr >2.5 in men and >2.0 in women

Decrease K+ supplementation and loop diuretic dose at time of initiation

Critical to monitor serum [K+] and renal function and check chem panel at 48 hours, 1 week, 4 weeks (because of this, many physicians don’t feel incentive to use aldosterone antagonist and follow patients carefully)

Avoid doses higher than 25 mg spironolactone qd and 50 mg eplerenone due to risk of hyperkalemia

66
Q

Beta blocker use in HF

A

Indicated for all pts with asymptomatic LVD dysfunction and for Class I to IV HF with LVEF <0.4

Contraindications: cardiogenic shock, severe airway disease, 2nd or 3rd degree heart block

Use the 3 evidence-based beta blockers: carvedilol, metroprolol succinate, bidoprolol

Monitor HR and BP

67
Q

Device therapy for HF

A

Cardiac resynchronization therapy (CRT)

Implantable cardioverter-defibrillators (ICD): good because remember 40% die due to arrhythmias causing sudden death!

Ventricular assist devices (bridge to transplant, destination therapy)

Totally implanted artificial hearts

Cardiac reshaping devices

Ultrafiltration devices

68
Q

CTR for HF

A

In patients with HF, 20-53% have IVCDs (RBBB, LBBB, IVCD)

Abnormal conduction (QRS widened) contributes to abnormal venricular activation/contraction and subsequent dysynchrony between RV and LV (reduced systolic performance, mechanical inefficiency, worsened prognosis)

Improves quality of life, functional status and exercise capacity

Reverse remodeling: decreased LV volume and dimensions, increased LVEF, decreased mitral valve regurg

Reduction in HF and all-cause morbidity and mortality

69
Q

Important comorbidities in HF

A

Cardiovascular: HTN, CAD, PVD, CVD, hyperlipidemia, a-fib

Non-cardiovascular: obesity, diabetes, anemia, CKD, thyroid disease, COPD/asthma, smoking, sleep disordered breathing, liver disease, arthritis, cancer, depression

70
Q

Patient education in HF

A

Monitor daily weight

Salt restricted diet (2gm Na+)

Medications, need for adherence

Activity Rx

Smoking cessation advice/counseling

What to do if HF symptoms worsen

Close follow-up and monitoring

71
Q

Heart failure with preserved LVEF

A

Treatment of patients with predominantly diastolic dysfunction HF not well studied, but still don’t have any tx!

Direct vasodilators not indicated

Diuretics used cautiously at low dose because still heart dependent on adequate preload

ACEI, Ca2+ channel blockers and beta blockers have favorable effects based on hemodynamics but impact on longer term outcome is not known

72
Q

Evidence-based treatment across continuum of LVD and HF

A

Reduce mortality: ACEI/ARB, beta blocker, aldosterone antagonist, ICD, CRT +/- ICD, Hyd/ISDN (in AAs)

Control volume: Na+ restriction, diuretics

Treat residual symptoms: digoxin

Treat comorbidities: aspirin, warfarin, statin

Enhance adherence: education, disease management, performance improvement systems

73
Q

Advances in treatment of HF

A

Increased attention to prevention

ACEI / beta blocker / aldosterone antagonist combination established as cornerstone of therapy

Evidence that beta blockers’ effects are not homogeneous (only 3 to use)

Downgrade in recommendation for use of digoxin

Integration of CRT and ICD device therapy into standard therapeutic regimen

Recognition that “special populations” of HF patients may benefit from or require different approaches (AAs using Hyd/ISDN)

New strategies to improve utilization of evidence based therapies

74
Q

Vasculitis

A

Inflammation in a blood vessel

75
Q

Primary systemic vasculitides

A

Chronic inflammatory disorders

Immune-mediated injury to blood vessels

76
Q

Giant cell arteritis (temporal arteritis)

A

Large and medium vessel vasculitis

Inflammation of aorta and extracranial branches leads to luminal narrowing or occlusion

Pathogenesis includes cellular immune responses but no autoantibody component

Symptoms from end-organ ischemia: headache, scalp tenderness, jaw claudication, blindness, vertigo (vertebral artery involvement), arm claudication with activity

Can also have thoracic aortitis with aneurysm, dissection, or rupture

Old age (75-85), women, polymyalgia rheumatica in 30-40%, impressively elevated ESR (>100)

Diagnose by large (2-3cm) superficial temporal artery biopsy (or bilateral biopsies)

Treatment: medical emergency treated with glucocorticoids (and low dose aspirin?)

77
Q

Takayasu’s arteritis

A

Large and medium vessel vasculitis

Most common in women 10-30

Common in Japan, SE Asia, India, Mexico

Panarteritic inflammatory infiltrates lead to luminal narrowing and occlusion: “pulseless disease,” BP discrepancies between arms, stroke, postural dizziness, seizures, HTN, cough, dyspnea, chest pain

Areas of aneurysmal dilation (development of aortic regurg)

Long-term prognosis influenced by CHF (aortic regurg, coronary artery involvement, HTN)

Treatment: GCs for initial control, methotrexate or azathioprine for relapsing disease, anti-TNF agents, arterial bypass surgery (prefer to perform when disease is quiescent)

78
Q

Polyarteritis nodosa (PAN)

A

Medium vessel vasculitis

Aneurysmal and stenotic lesions of muscular arteries at branch points: renal (HTN and anemia), heart, nervous system, GI

Associated with HepB, HepC, HIV

Treatment: remissions or cures in 90% of pts treated with corticosteroids and cyclophsophamide

79
Q

Kawasaki disease

A

Medium vessel vasculitis

Often seen in children younger than 5

Notable (and testable) for coronary artery involvement (most common cause of pediatric acquired heart disease in US)

Diagnosis: fever x 5 days plus conjunctival injection, oropharyngeal changes, peripheral extremity desquamation, polymorphous rash, cervical lymphadenopathy

Treatment: IVIG, aspirin (yes, even in children!)

80
Q

Thromboangitis Obliterans

A

AKA Buerger Disease

Medium and small arteries

Segmental, thrombosing acute and chronic inflammation in tibial and radial arteries

Raynaud’s phenomenon often present

Pathogenesis: direct endothelial cell toxicity by a component of tobacco

Treatment: smoking cessation

81
Q

What do HF patients die of?

A

40% progressive worsening HF

40% sudden death due to arrhythmia

82
Q

Is digoxin important to use in HF?

A

NO!

Digoxin actually did not improve survival or total hospitalization!

83
Q

Prophylactic/preventative ICD

A

Improves survival in those with reduced EF

But is very expensive

84
Q

Wegener’s Granulomatosis (WG)

A

AKA granulomatosis with polyangitis (GPA)

Small vessel vaculitis

Males more than females

Average age of onset 40

Possibly induced by T cell-mediated hypersensitivity reaction to inhaled agent

Clinical: sinus disease, upper airway disease, lung involvement, kidney involvement, less common but clinically relevant are orbital pseudotumor (–> proptosis) and otitis media

ANCA+ in 90% with renal involvement but less with limited disease (upper airway only), usually C-ANCA anti proteinase-3 type

However, since ANCA+ in fungal, bacterial or mycobacterial pulmonary infections, this doesn’t make the dx–need tissue dx

Treatment: GCs, cyclophosphamide, new data on rituximab, consider plasmapheresis for diffuse alveolar hemorrhage or RPGN

85
Q

Churg-Strauss Syndrome (CSS)

A

Small vessel vasculitis

Allergic granulomatosis and angitis

Theoretical cause: hyper-responsiveness to allergic stimulus

Clinical: new-onset asthma or previously stable asthma that unexpectedly becomes uncontrollable, sinusitis (not destructive like in WG), allergic rhinitis, palpable purpura, cardiomyopathy from infiltration of eos, FSGS

Labs: peripheral eosinophilia, fleeting infiltrates on CXR, P-ANCA anti-myeloperoxidase antibodies often positive

Diagnosis made by tissue biopsy, and vascular lesions show granulomas and eosinophils

Treat with corticosteroids

86
Q

Microscopic polyangitis

A

AKA hypersensitivity vasculitis

Small vessel vasculitis

Necrotizing glomerulonephritis (no granulomas) and pulmonary capillaritis are particularly common

Cutaneous and neurologic involvement common

Alveolar hemorrhage characterizes lung involvement

P-ANCA anti-myeloperoxidase antibodies +

Treat with steroids and cyclophosphamide

87
Q

Henoch-Schonlein Purpura

A

Small vessel vasculitis

Chileren with medial age of onset 4 but can see at any age

Palpable purpura in 100% of patients

Arthritis in large joints, abdominal pain (intestinal ischemia), hematuria

Treatment supportive

88
Q

Things that mimic primary systemic vasculitis

A

Syphilitic aortitis

Giant syphilitic aortic aneurysm

Cholesterol emboli after coronary angioplasty

Infective endocarditis (peripheral manifestations)

Lupus-associated intestinal vasculitis

Severe digital ischemia

Calciphylaxis with arterial calcification

Peripheral artery disease

89
Q

Consequences of longstanding poorly controlled systemic HTN

A

LV hypertrophy

Acceleration of CAD

Renal failure

Strokes

Visual impairment

90
Q

Malignant HTN

A

Only small minority of patient develop this

Extremely elevated pressures with retinal hemorrhages, CVAs, renal failure, mental status changes

Endothelial dysfunction with intimal hyperplasia

Requires acute inpatient therapy

Treatment differs significantly from treatment of primary or essential HTN

91
Q

Thiazide diuretics as first line for HTN

A

Thiazide diuretics effective alone and also can be used as supplemental therapy for pts unresponsive to multiple medication combinations

Patients may become refractory to drugs that block SNS or vasodilators because drug effect seems to become volume dependent (thiazides reduce volume)

Thiazides increase LDL, total cholesterol and TG –> increased risk of CAD

In diabetics, effect on glucose and LDL makes selection of alternative (non-thiazide diuretic) first line more attractive

92
Q

Vasodilators

A

ACE inhibitors

ARBs

CCBs

Beta blockers

Nitroprusside

Hydralazine

Minoxidil

93
Q

Calcium channel blockers

A

Relaxing effect on arteriolar smooth muscle and decreased SVR

Inhibits entry of Ca2+ into vascular smooth muscle cells so cannot do vasoconstriction (instead vasodilate)

3 classes of CCBs: phenylakylamines (verapamil), dihydropyridines (nifedipine, amlodipine), benzothiazepines (diltiazem)

Adverse effects: flushing, headaches, lower extremity edema (dihydropyridines), constipation, AV node effects can lead to bradycardia and heart block; adv eff exacerbated by concurrent administration of beta blocker

Effective and safe in selected populations

Unlike thiazides, do not have adverse effects on lipid levels, electrolytes, or glucose tolerance and have no adverse effect on renal function

Included as potential first line agent in JNC7, and may be useful as well-tolerated add-on agent

94
Q

Body’s reaction to CCBs

A

CCBs cause vasodilation, which stimulates sympathetic nervous system

This compensatory response causes hypotension

Excess hypotensive effect can be seen if compensatory mechanisms (alpha and beta) stimulation are pharmacologically blocked

95
Q

Short acting CCBs

A

Were shown in 1990s to be associated with increased CV events

Immediate release dihydropyridine used in these pts associated with 2.5 times increased risk of death compared with placebo

Possible mechanisms relate to activation of SNS

Recent studies endorse safety of longer acting agents but more studies needed

96
Q

Mechanisms of beta blockers

A

Blockade of cardiac beta receptors results in decreased myocardial contractility and cardiac output

Changes in control of SNS within CNS

Increased prostacyclin biosynthesis

Changes in baroreceptor sensitivity

Reduced renin (since beta 1 adrenergic stimulation stimulates renin secretion from JGA) results in decreased ATII

Adverse effects: in asthmatics, exacerbation of bronchospasm can be seen, in pts with profoundly reduced LVEF and CHF, can trigger HF episode (but benefit of low dose beta blockers!), development of SA and AV nodal block so avoid in pts with pre-existing heart block, cautious with insulin treated diabetics who become hypoglycemic because mask symptoms of hypoglycemia

97
Q

Classifications of beta blockers

A

Grouped based on lipid solubility, presence or absence of intrinsic sympathetic activity, and selectivity for beta 1 and beta 2 receptors

Beta 1 selective: metoprolol, atenolol

Lipophilic (crosses BBB and can produce depression, nightmares): propranolol

98
Q

Special considerations for specific beta blockers

A

Use beta 1 selective agent (metoprolol, atenolol) in patients with COPD to prevent beta 2 stimulation and bronchoconstriction

Use non-lipophilic (metoprolol, atenolol) in patients with depressive symptoms (also less sexual side effects)

99
Q

Hydralazine

A

Directly relaxes arteriolar (not venous) smooth muscle

Resulting selective arteriolar vasodilation stimulates SNS which increases renin, increases HR and contractility, fluid retention

Risks include “steal ischemia”, drug induced lupus, flushing, headaches

Given as bolus (not IV infusion), so difficult to titrate

100
Q

Alpha 1 blockers

A

Prazosin, doxazosin, terazosin

Decreased arteriolar resistance

Reflex increase in sympathetic tone and plasma renin at first but then vasodilation remains but renin, HR and CO return to normal

101
Q

Alpha 2 agonist

A

Clonidine, methyldopa

Alpha 2 agonist stimulates alpha 2 receptors in brainstem resulting in decreased sympathetic efferent outflow (decreased NE release by alpha 2 receptors)

CO and PVR reduced resulting in decreased BP

Used in HTN but not typically first line due to side effects

Rebound HTN is a problem with abrupt discontinuation of clonidine

102
Q

Methyldopa

A

Not widely used, but safe in pregnancy

103
Q

Antihypertensives during pregnancy

A

If taken before pregnancy, most antihypertensives can be continued, except ACEI and ARBs

Methyldopa is most widely used when HTN detected during pregnancy

Labetolol and Nifedipine also used during some pregnancies complicated by HTN

104
Q

Antihypertensives in AAs

A

Diuretics shown to decrease morbidity and mortality and should be first choice

CCB may be good choice

Patients may not respond well to monotherapy with beta blockers or ACE inhibitors

105
Q

Antihypertensives in elderly

A

Smaller doses, slower incremental increases and simple regimens should be used

Close monitoring for side effects (deficits in cognition after methyldopa; postural hypotension after prazosin)

106
Q

Antihypertensives in hyperlipidemics

A

Low dose diuretics have little effect on cholesterol and TGs

Alpha blockers decrease LDL/HDL ratio

CCBs, ACEIs, ARBs have little effect on lipid profile

107
Q

Antihypertensives in DM

A

ACEI, alpha antagonists and CCBs can be effective and have few adverse effects on carbohydrate metabolism

108
Q

Antihypertensives in severe obstructive airway disease

A

Avoid beta blockers!

109
Q

Malignant HTN

A

Neurological: hypertensive encephalopathy, CVA;CI, SAH, ICH

Cardiovascular: MI, acute left ventricular dysfunction, acute pulmonary edema, aortic dissection

Acute renal failure/insufficiency

Retinopathy

Eclampsia

Microangiopathic hemolytic anemia

110
Q

Drugs for hypertensive emergencies

A

Labetalol: alpha and beta blocking

Nicardipine (Ca2+ channel blocker): influx of Ca2+ during depolarization in arterial smooth muscle, reduces mean arterial BP by decreasing SVR

Esmolol: beta blocker, can titrate

Nitroprusside: dilates both venules and arterioles (venules a little more but not as much as nitroglycerin; use when BP way off the charts because very strong); decreases SVR via direct action on vascular smooth muscle

111
Q

Why do cardiac myocytes hypertrophy?

A

Cell cycle reentry is blocked (when cardiac myocytes damaged they have no way of regenerating!)

Stress

Injury growth signal

112
Q

Physiological vs. pathological stimuli for cardiac hypertrophy

A

Physiological: athletes, pregnancy; increase in myocyte length more than increase in width

Pathological: extrinsic stimuli (increased afterload: HTN, aortic stenosis; myocardial injury: MI, myocarditis), intrinsic stimuli (mutations of sarcomeric proteins: hypertrophic cardiomyopathy; mutations of dystrophin complex: Duchenne’s muscular dystrophy), endocrine disorder; increase in myocyte length less than increase in width

113
Q

Physiological hypertrophy (athlete’s heart)

A

Physiological hypertrophy is normal adaptive response to increased hemodynamic demands

Increased LV wall thickness and myocyte size

Increase in stroke volume and maximum cardiac output: EDV increases but ESV remains same

Decrease in resting HR, however resting CO remains the same due to increased SV

114
Q

Familial hypertrophic cardiomyopathy

A

Autosomal dominant

Hypertrophied and nondilated left ventricle in absence of other predisposing etiology (eg HTN, aortic stenosis)

LV is normally hypercontractile (contraction is good but relaxation is not and that’s why you have elevated pressure for any given volume)

Uncommon incidence (0.1%)

Most common cause of sudden cardiac death in adults <30 yrs old (due to arrhythmia)

Asymmetrically enlarged septum

115
Q

Symptoms of hypertrophic cardiomyopathy

A

Symptoms related to hypertrophy itself (diastolic dysfunction), or outflow obstruction (increased afterload):

Dyspnea: decreased LV compliance, increased LVEDP causes increased PCWP which makes you SOB

Angina: myocardial flow-demand mismatch

Fatigue: decreased CO, decreased SV, decreased relative preload

Arrhythmias: increased risk of sudden death particularly with strenuous physical exertion

A-fib: increased LVEDP causes increased LA size which can cause a fib

116
Q

What people with HCM have, but athletes don’t

A

Unusual patterns of LVH

LV cavity <45mm (athletes are >55mm)

LA enlargement

Bizarre ECG patterns

Abnormal LV filling

Female

Family hx HCM

Note: athletes have decreased thickness with deconditioning and max VO2 ?50ml/kg/min and ?120% predicted

117
Q

Linkage of HCM to myosin heavy chain gene

A

Beta myosin heavy chain

Also linkages shown with troponin-I, troponin-T, alpha troponin, cardiac myosin binding protein C, essential myosin light chains, regulatory myosin light chain

118
Q

Treatment for hypertrophic cardiomyopathy

A

Treatment is controversial: avoid high intensity athletics

Medications to reduce contractility: beta blockers, Ca2+ channel blockers (but don’t know if this is sufficient long-term)

Implantable defibrillators

Surgical reduction of septal hypertrophy: myomectomy (cut out muscle from hypertrophied septum to relieve obstruction), septal alcohol ablation (inject down septal artery which kills off muscle in septum/scars and gets thinner and aleviates hemodynamic problems) but these do not alleviate problem of sudden death

119
Q

What things cause myocardial injury/stress

A

Hypertension (increases afterload; most common cause of hypertrophy but not hypertrophic cardiomyopathy and not physiologic)

Viral

Ischemia

Toxins

Valvular

Post partum

120
Q

Hypertension and end-organ damage

A

Brain and blood vessels: atherosclerosis, vasoconstriction, vascular hypertrophy, endothelial dysfunction (all can cause stroke)

Heart: LV hypertrophy, fibrosis, remodeling, apoptosis (all can cause MI and heart failure)

Kidney: GFR, proteinuria, aldosterone release, glomerular sclerosis (all can cause renal failure)

121
Q

Clinical complications associated with LVH

A

Increased mortality

CAD

CHF: diastolic dysfunction, systolic dysfunction

Arrhythmias: atrial fibrilation (stroke), PVCs, ventricular tachycardia

122
Q

Laplace’s Law

A

Wall tension = (P x r)/2w

P = pressure

r = chamber radius

w = wall thickness

In HTN, pressure increases so wall tension increases

In compensatory hypertrophy, pressure increases so wall thickness increases to bring pressure back down

123
Q

What is the link between wall stress and gene changes seen in LVH?

A

Injury causes wall stress which causes ATII release (from cardiac myocyte itself), which causes gene expression, protein synthesis and apoptosis in the cardiac myocyte

124
Q

Cellular and molecular changes in hypertrophied myocytes

A

Pathologically hypertrophied myocytes are not just big cells!

Still organized like normal heart cells though (unlike familial hypertrophic cardiomyopathy disarray!!)

Sarcomeric proteins:

Decreased alpha-MHC and increased beta-MHC: beta-MHC has decreased ATPase activity; although cycling requires less energy now, also get decreased contractile strength and velocity of contraction

Increased troponin T2: strengthens tropomyosin-actin interaction and inhibits cross-bridge formation and cycling

Calcium handling genes:

Decrease number of L-type Ca2+ channels

Uncoupling of L-type Ca2+ channels and Ryanodine receptors

Decrease sarcoplasmic reticulum CaATPase and decrease phospholamban phosphorylation, which decrease SR Ca2+ uptake during relaxation

Beta-adrenergic signaling: decreased beta-1 receptor density and function

Increased susceptibility to apoptosis (progressive myocyte loss and replacement fibrosis)

125
Q

Natural history of cardiac hypertrophy

A

HTN –> increased SVR –> abnormal Na/water, increased vasoconstricting factors (ATII, SNS, endothelin), decreasing vasorelaxing factors (NO, PGI, ANF), increased vascular growth factors (IGF, TGF-beta, FGF)

Increasing wall tension leads to hypertrophy

As myocardium hypertrophy develops, get diastolic dysfunction with preserved contractility (maybe even better contractility) but decreased compliance (LVH) so smaller SV = causes SOB

Systolic dysfunction with impaired contractility and decreased CO (dilated cardiomyopathy) after apoptosis

Note: diastolic dysfunction has decreased CO and SV because smaller chamber but systolic dysfunction has smaller SV and CO because decreased contractility

126
Q

Treatment for heart failure

A

Determined by severity of symptom and underlying cause

First step: fix reversible causes: revascularize if necessary, remove “toxins” (ETOH, cocaine), correct endocrinopathy (hyperthyroidism)

Second step: lifestyle modifications

Third site: drug therapy

Fourth step: transplant, cell therapy or mechanical device

127
Q

Diuretic effects

A

Decrease volume and preload: improve symptoms of congestion

No direct effect on CO but excessive preload reduction may reduce CO –> leads to cardiorenal symdrome (decreased GFR, increased creatinine and diuretic resistance)

Neurohormonal activation (except spironolactone): increase SNS, increase ATII, increase vasopressin

128
Q

Positive inotropes

A

Cardiac glycosides (digoxin): +/- contractility, does not increase mortality

Beta agonists (dobutamine): increase contractility, increase HR, increase arterial pressure (?), increase arrhythmias, increase mortality

Phosphodiesterase inhibitors (PDIs): increase contractility, increase HR, increase arterial pressure (?), increase arrhythmias, increase mortality

Note: don’t give these to someone with hypertrophic cardiomyopathy because they have good contractility still; give to someone with dilated cardiomyopathy to increase contractility (but only for short time because increases mortality)

129
Q

Physiological effects of vasodilator therapy

A

Venodilation (nitroglycerine): decrease preload (decrease pulmonary congestion, decrease ventricular size, decrease ventricular wall stress, decrease myocardial work and O2 consumption)

Coronary vasodilation: increase myocardial perfusion

Arterial dilation: decrease afterload (increase CO, decrease BP)

130
Q

Neurohumoral adaptive responses to decreased CO and decreased BP

A

Short term: activation of SNS

Long term: activation of RAAS, increased vasopressin, increased ANP/BNP

Perhaps neurohormones have a direct “toxic” effect on myocardium (specifically ATII and RAAS!)

131
Q

Heart failure therapies proven to reduce mortality and/or symptoms

A

Mortality and symptoms: ACEI (+/- ARBs), beta blockers, aldosterone antagonists, nitrates/hydralazine (note ACEI better than hydralazine/ISDN), devices (AICD, biventricular pacers, left ventricular assist devices)

Symptoms: digoxin, diuretics

132
Q

Novel HF therapies

A

Stem cells (cardiac derived, bone marrow, iPS)

Gene therapy: SERCA (pump that gets Ca2+ back into SR) overexpression, AC6 (increase cAMP, could be helpful could cause arrhythmia) overexpression

133
Q

What is it that causes sudden death in people with HCM?

A

Arrhythmia

Myofibrils are in disarray which sets up areas where electrical conduction through myocardium not smooth, get reentrant foci which can lead to v-tach or v-fib

Also, SNS is a drive for arrhythmia, so these two together (guy with HCM playing basketball) cause sudden death

134
Q

What are the best drugs to treat essential HTN?

A

“ACD”

ACEI

CCB

Diuretic

Add 4th agent (aldosterone antagonist) if necessary

135
Q

Nesiritide

A

Recombinant BNP, available only IV

Effective as adjunct to loop diuretics for more rapid reduction of wedge pressure and diuresis in patients with markedly elevated wedge pressure

Arterial and venous dilator, antagonizes neurohormones

Caution if BP<90 (contraindicated) since main side effect is hypotension

200x the price of nitroprusside and nitroglycerine! And may not be that much more efficacious

136
Q

Changes seen in heart failure

A

Decreased effective circulating volume causes decreased GFR, which:

Stimulates Na+ reabsorption in PCT

JGA increases renin release which increases ATII and aldosterone (reabsorption of Na+ in collecting duct)

As a result, BNP is secreted to counteract effects by inhibiting Na+ reabsorption at distal tubules

Block 9: Cardio, Renal and Resp II (8 decks)

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