SHA24/080001

Waleed AlHabeeb, MD Consultant Heart failure A nd Transplant Cardiologist King Faisal Specialist Hospital

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Compared with the LV, the RV has a different embryologic origin

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Undergoes a dramatic change during the transition from fetal to adult circulation

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Normally operates in a low resistance or impedance arterial system

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The RV exhibits lower oxygen requirements at rest and exercise, lower resting coronary blood flow, greater systolic coronary flow, ineffective pressure flow regulation, greater effect of flow and pressure on oxygen consumption, less coupling between flow and contractile function

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Nitric oxide regulates resting right, but not left, coronary blood flow

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α–adrenergic stimuli and exercise selectively induce right coronary constriction

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The compensatory phase during increased afterload is significantly shorter in the RV compared with the LV Increased mortality observed in patients with PAH compared with patients with systemic hypertension Same with acute increases in the afterload: cardiovascular collapse is not uncommon with massive pulmonary embolism Extremely rare in patients with hypertensive emergency

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Despite maladaptive right ventricular remodeling, the RV retains an amazing ability for reverse remodeling once the stressor has been removed

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Two examples of chronic pressure-overload states that are well tolerated by the RV: Eisenmenger syndrome congenital pulmonary stenosis

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CHEST 2005; 128:1836

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RV failure is a complex clinical syndrome that can result from any structural or functional cardiovascular disorder that impairs the ability of the RV to fill or to eject blood

The cardinal clinical manifestations of RV failure are (1) fluid retention, which may lead to peripheral edema, ascites, and anasarca; (2) decreased systolic reserve or low cardiac output, which may lead to exercise intolerance and fatigue; or (3) atrial or ventricular arrhythmias 

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HEART FAILURE!!

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In the failing RV, excessive sympathetic adrenergic stimulation may adversely affect ventricular remodeling and Survival

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Decrease in β-adrenergic receptor density in the stressed RV such as that occuring in the left ventricle (LV)

Prognostic implications

Ghio et al. J Am Coll Cardiol 2001;37:183– 8

P. Meyer et al. / International Journal of Cardiology 155 (2012) 120–125

Meyer et al

Circulation. 2010;121:252-258

Haddad et al.

J Heart Lung Transplant 2009;28:312–9

Am J Cardiol 2010;105:1030 –1035

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Adequate RV function is critical for a patient to do well with left ventricular (LV) support alone

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The incidence of RV failure varies in the literature not only by era and by device, but also by the definition of RV failure

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In the era of pulsatile pumps, the rate of RVAD use was 4-25%, and the rate of overall RV failure was 10-39%

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In the current era of continuous flow pumps, there is a lower incidence of RV Failure

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In trials of both axial flow and centrifugal flow devices, there is a 4-6% incidence of RVAD use and a 13-20% incidence of the need for prolonged inotropes

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The impact of MCS on RV function can be both beneficial and detrimental

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The beneficial effects are realized through unloading the left ventricle and decreasing filling pressures, reducing RV afterload

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The potential detrimental effects include an increase in RV preload from the normalized cardiac output, and the septal shift observed with unloading the left ventricle

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RV dysfunction after MCS leads to high levels of morbidity and mortality, longer lengths of stay, and worse post-transplant outcomes

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Biventricular support, although a reasonable option when necessary, requires a more extensive surgery, has a worse device patient interface than LV support alone

“Never Mistake Motion for Action”

(Ernest Hemingway 1832-1898)

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An RV that appears severely dysfunctional by echocardiography may still be able to maintain low right atrial filling pressures and generate high pulmonary pressures

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Conversely, a mildly dysfunctional RV by echocardiography may be severely compromised when hemodynamics are invasively assessed

Invasive Assessment of RV

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Invasive hemodynamics allow the calculation of RV stroke work index (RVSWI):

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RVSWI = [mean pulmonary artery pressure (PA) – mean right atrial pressure (RA)] x [cardiac index (CI)/heart rate (HR)]

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RVSWI of <300 predictive of RV failure

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In the setting of marginal RV function, hemodynamically guided therapy with a Swan-Ganz catheter in an ICU setting for several days may be needed to determine if the patient can be managed with MCSD alone or will need biventricular support

Fitzpatrick JR et al. J Heart Lung Transplant 2008;27:1286-92.

Matthews JC et al. J Am Coll Cardiol 2008;51:2163-72

Management of RV Failure

Class I:  RV dysfunction post MCS should be managed with diuresis, inotropes and pulmonary vasodilators including nitric oxide or inhaled prostacyclin. RV dysfunction refractory to medical management may require placement of a short or long term mechanical RV support device. Level of Evidence: C. Class IIb:  Phosphodiesterase 5 inhibitors may be considered for management of RV dysfunction post MCS. Level of Evidence: C. J Heart Lung Transplant 2013;32:157–187

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All inotropes concomitantly target the left ventricle Dobutamine is the inotrope traditionally used in cardiac pump failure Dobutamine vs norepinephrine The combination of dobutamine and inhaled nitric oxide (iNO) improved CO, decreased PVR, and increased the PaO2/FiO2 ratio

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Milrinone, a selective phosphodiesterase (PDE)-3 inhibitor, also exerts inotropic and vasodilatory properties Decreasing PVR and increasing RVEF in acute and chronic PH Use is limited by systemic vasodilation and hypotension Like dobutamine, milrinone can be combined with iNO to augment pulmonary vasodilation while minimizing hypotension and tachyarrhythmias

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It is possible that therapies for LV dysfunction might be beneficial in treating the dysfunctional RV

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The renin-angiotensin-aldosterone system plays an important role in the pathophysiology

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It is not known whether the use of the particular agents will have a clinical benefit

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Lowering systemic blood pressure could worsen cardiac output in PH through ventricular-interdependence

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Negative inotropes, such as β-blockers, have

traditionally been avoided in PH owing to reports of sudden decompensation and death

E. Tatli et al. International Journal of Cardiology 125 (2008) 273â&#x20AC;&#x201C;276

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Modulation of the endothelin system with endothelin receptor antagonists in PAH may lead to an improvement in exercise capacity, a decrease in pulmonary vascular resistance, and better ventricular remodeling

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In contrast, endothelin receptor blockade in left HF did not lead to significant clinical benefits even though endothelin levels are often elevated in left HF

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Prostacyclins activate cyclic adenosine monophosphate, resulting in pulmonary and systemic vasodilation Improves end points in pulmonary arterial hypertension Prospective data on critically ill patients with acute RVF are sparse

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PDE5 is not expressed in the normal, nonhypertrophied RV

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RV hypertrophy sharply induces RV PDE5 expression

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PDE5 inhibition significantly increases RV contractility

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The mechanism is likely cGMP inhibition of the cGMP-sensitive PDE3 isoenzyme that normally metabolizes cyclic adenosine monophosphate (cAMP) and a resultant increase in cAMP with its attendant positive inotropic stimulatory effects

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It is debatable whether sildenafil exerts its therapeutic effects via its action on the pulmonary vasculature (e.g. afterload unloading) or by a direct antihypertrophic effect on RV remodeling

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Sildenafil has also unique lusitropic and inotropic effects in the hypertrophied RV

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Considering contractile function in isolation may fail to contribute to our understanding of RV performance in clinical practice and in trials

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We need to consider the whole heart response rather than focusing exclusively on specific aspects of RV function

Thank You