Pharmacologic Support of Cardiac Failure Portrait of Dr. Gachet- vanGogh (1890)

Objectives Pathophysiology of cardiac failure Pharmacology Therapeutic approaches Novel concepts Focus on Critical Care setting

Cardiac Failure Classification Cardiac Cycle –Systolic vs Diastolic Heart Side –Right vs Left

Systolic vs. Diastolic Systolic- Diminished ventricular contractility Diastolic- Diminished ventricular distensibility/passive relaxation (Lusitropy) –Ventricular hypertrophy –Myocardial ischemia (“Shock heart”) –Cardiac tamponade –Positive Pressure Ventilation End Diastolic Volume (not pressure) is the distinguishing factor

Right Ventricular Dysfunction Predominantly systolic in nature Characterized by increased CVP –CVP ≥ PCWP Enlargement of RV  bulging of septum into LV…interventricular interdependence Serum BNP (Brain-type or Atrial Natriuretic Peptide) –Systemic vasodilators, increase renal Na excretion –Sensitive marker (>100 pg/mL) –Accurate measure of degree of HF

LV Dysfunction in the ICU 1/3 of pts in ICU will develop LV Dysfunction Cardiac Myocyte Insults –Catecholamines –Inflammatory mediators –Endotoxins –Cardiac contusion –Hypoxia/hypoperfusion –The role of stress?

RV Dysfunction More common than suspected Usually systolic failure Ventricular pressures remain normal bc ventricle can stretch  until pericardium impedes it TEE to measure RVEF Specialized Swan-Ganz catheters

Cardiac Dysfunction Absence of CAD Unmasking of subclinical cardiac disease

LEFT-SIDED HEART FAILURE Paul L. Marino. The ICU Book. 3 rd Ed p

The Vicious Cycle Inc. Preload Inc. Transmural pressure  squeezed coronaries Diminished CO Increased Preload Increased Afterload Transmural pressure Ischemia…

Vasodilators Nitrates –Nitroprusside –Nitroglycerin Nesiritide (Natrecor)- recombinant BNP

Nitroprusside (Nipride) Systemic vasodilator –Arterioles > Venules Half-life: 1-2 min (thyocyanate  excretion in days) Caution: –Cyanide Toxicity –Coronary Steal Syndrome

Nitroglycerin Systemic vasodilator (and an explosive) –Veins > Arteries –Low dose: Venous dilation  can further reduce CO Tolerance- can appear w/in 24h with continuous infusion Avoid in uncorrected anemia, hypovolemia, head trauma, tamponade

Nesiritide (Natrecor) Recombinant human BNP –Stimulates cGMP  Vasodilation, Natriuresis/Diuresis Avoid in hypotension

Adrenergic Agonists Dobutamine Dopamine Milrinone

Dobutamine Beta-1-receptor agonist Inotropy +++ Chronotropy +++ Reduces afterload (vasodilation)  end organ perfusion Half-life- 1-2 minutes Increases myocardial O2 consumption  danger in ischemic heart

Dopamine D1 and Beta-1-receptor agonist –<3  Splanchinc vasodilation (D1) Natriuresis induction in kidneys –3-7 mcg/kg/min  Inotropy +++ (B-1) –>7mcg/kg/min  vasoconstriction  afterload increase –>10  Systemic pressure support (Alpha-1)

Milrinone (Primacor) Phosphodiesterase inhibitor (PDEi) –Chronotropy –Inotropy –Lusitropy Venodilator/Arteriodilator –Used in pulmonary HTN Half-life 1-2 hrs Negative effect on mortality in hospitlized pts (long-term treatment of chronic disease) MS Cuffe et al. Short term IV Milrinone for the acute exacerbation of chronic CHF: A prospective randomized trial. JAMA 2002 Mar 27

Blood Pressure High BP Cardiac Failure –Afterload Reduction  Vasodilators –Diuretics if unresponsive Normal BP Cardiac Failure –Inodilators  Dobutamine/Milrinone/Epi –Diuretics if unresponsive Low BP Cardiac Failure (Decompensated) –Pressure restoration  Dopamine –Vasoconstrictive, inotropic

Diuretics IV Furosemide can drop CO 15-20% Can worsen decompensated HF Indicated if PCWP remains > 20 mmHg despite other agents Mainstay of Tx in Trauma population #1 Augmentation of CO Diuresis occurs naturally as renal perfusion improves (eliminate the need to retain Na & H2O)

Levosimendan (Simdax) IV “inodilator” (Dobutamine, Milrinone) –Calcium sensitizer –Opens ATP-sensitive K+ channels in vessels Augments CO via –Positive inotropy –Systemic vasodilation Cardioprotective from ischemia

Other Agents Thyroid Hormone –“Sick Euthyroid” patient –Enhances cardiac recovery after ischemia Methylene Blue –Experimental benefits –Inhibits NO production, halts SIRS response? –May be useful in septic shock –Pulmonary vasoconstriction?

Takotsubo Cardiomyopathy “Broken Heart Syndrome” Tako-tsubo. (Jap.) “Fishing pot for trapping octopus” “Stress-Cardiomyopathy” severe emotional or physiologic stress, typically in elderly, in the absence of coronary disease Catecholaminergic insult to cardiac myocytes Supportive care = complete resolution

Tako-Tsubo Dilated apex with basilar cardiac contraction