The Cardiac Side of the Cardio-Renal Dilemma Dr. Ellie Stadnick MD MSc FRCPC Cardiologist University of Ottawa Heart Institute May 9, 2016

Patients with refractory heart failure should be offered chronic dialysis… maybe….

Disclosures Advanced Heart Failure Cardiologist I actually like nephrology I prescribe more furosemide than I care to admit

HF is Common and Costly The most common reason for hospitalization in the elderly Major driver of cost is hospitalizations Population Group Prevalence Incidence Mortality Hospital Discharges Cost Total population 5,000,000 550,000 >55,000 >1,000,000 >$35 billion

HF Prognosis 1.0 0.8 0.6 0.4 0.2 Survival No HF (n=1728) NYHA Class I (n=36) NYHA Class II (n=79) NYHA Class III (n=62) NYHA Class IV (n=59) 1 2 3 4 5 6 Time after inclusion (yrs) NYHA = New York Heart Association Smith WM. Am J Cardiol 1985;55:3A-8A.

The 2 x 2 Matrix of CHF WET DRY WARM WET + WARM DRY + WARM COOL WET + COOL DRY + COOL

Nohria et al. J Am Coll Cardiol. 2003;41(10):1797-1804.

Frank-Starling Relationship

The Relationship Complex interplay between the heart and the kidneys

The Kidney for Cardiologists Low cardiac output to kidney leading to reduction in GFR (Pre-renal). Too much venous congestion leading to impaired renal perfusion (Too Much “back-pressure”) Diuresis causing intravascular depletion (Too Much Too Fast) Prolonged pre-renal leading to kidney injury (renal/ATN). Intrinsic renal disease secondary to hypertension or diabetes found in many of cardiac patients.

Cardio-Renal Syndrome One view used to be that CRS is caused by a weak heart unable to provide enough forward flow to essentially cause ‘pre-renal’ failure It is more complex than that A recent classification scheme describes 5 subtypes (Ronco et al. JACC 2008;52:1527-39)

CRS 1 – Acute decompensated HF

CRS 2 – Chronic HF

CRS 3 – AKI causing HF

CRS 4 – CKD causing HF

CRS 5 – Systemic dz affecting both

Ways to Break the Cycle 1. Improve the Loading Conditions: Decongest More aggressive diuresis (IV, sequential nephron blockade) Nitrates Dialysis/Ultrafiltration if oliguric despite all efforts

Diuretic Resistance

Diuretic Resistance JACC 2010;56:1527-34

Ways to Break the Cycle 2. Improve Forward Flow Decrease Afterload ACEi/ARB (not ideal in AKI) Nitrates/Hydralazine Increased contractility Digoxin (not in AKI) Inotrope IV infusions Revascularization options (ideally not in AKI) Cardiac Transplantation? Important Renal Considerations!

Medications in Systolic Heart Failure ACE inhibitors/ARBS Beta-blockers Aldosterone Antagonists Diuretics (possibly) Digoxin (possibly) Nitrates (possibly) Hydralazine (possibly)

ACE inhibitors and ARBs MORTALITY BENEFIT in systolic heart failure along with anti-remodeling benefits. Short term may worsen GFR (due to efferent arteriole dilation) and increased risk of hyperkalemia. Long-term preserves GFR in patients with CKD.

Beta Blockers MORTALITY BENEFIT in systolic heart failure. Chronic management strategy; NO role in the acute setting May consider stopping them if inotropic support is required.

Aldosterone Antagonists MORTALITY BENEFIT in systolic heart failure Examples: Spironolactone and Eplerenone Be mindful of potassium levels

Diuretics NO MORTALITY BENEFIT, but improve symptoms of congestion. Will need higher doses (+/- second diuretic for synergistic effect) to achieve adequate diuresis in CKD patients. Such a strategy may result in an elevation in serum creatinine. If there is significant congestion; however, aggressive diuresis may actually improve LV function and decrease venous congestion thereby improving renal perfusion leading to improved GFR

Digoxin NO MORTALITY BENEFIT, BUT REDUCES SYMPTOMS AND HOSPITALIZATIONS Renal clearance and so risky to use in people with CKD, especially in those with fluctuating renal function. Risk for digoxin toxicity and lethal arrhythmias especially with electrolyte abnormalities that often accompany CRS

Hydralazine and Nitrates Preferential arterial dilator used to treat hypertension. Helpful for after-load reduction. When coupled with nitrates in A-HeFT trial had mortality benefit in addition to beta-blockers and ACE inhibitors. Nitrates Primary venodilators and some arterial dilation In A-HeFT trial given orally, but can be transdermal or IV infusion. Reduce preload and after-load, both in an attempt to unload a failing heart. .

Inotrope therapy Small trials have shown dobutamine to decrease renal sympathetic activity and increase renal plasma flow rate and GFR (Al-Hesayen et al. Journal of Cardiovascular Pharmacology May 2008, Vol 51) Dobutamine, Milrinone: Role is controversial. Short term use often used for rescue; however inotrope use is associated with increased mortality

Acute Management Hold ACEi/ARB Hold Spironolactone Usually will continue beta blocker at current dose or half-dose

Acute Management Step one: Step two: Step three: Assess volume status (wet or dry?) Do you need a PA Catheter ? Step two: Assess Perfusion (warm or cold?) Step three: Initiate therapy COLD: INOTROPES/VASODILATE WET: REMOVE FLUID

Acute Management Step four: Step five: If still volume overloaded (and creatinine is rising) …DIALYSIS INDICATION…. Step five: LVAD or other mechanical circulatory support What would this patient want? What is the long term plan?

Chronic Management Is there any role for revascularization by PCI or CABG? Consider higher risk of contrast nephropathy in patients with CKD Consider increased surgical risk in patients with CKD

A Word About CRT Cardiac Resynchronization Therapy. Ideally indicated in severe LV systolic dysfunction with a wide LBBB on ECG. Pacing the left and right ventricles simultaneously may improve overall cardiac function and forward flow.

End of the Line Circ J 2011; 75

End of the Line Slaughter MS et al. N Engl J Med 2009;361:2241-2251

End of the Line If patients like this continue to have parameters of impaired perfusion despite volume removal and pharmacologic optimization, then device therapies or cardiac transplantation may be considered. Unfortunately, unless renal function is recoverable, these patients are often not candidates for cardiac transplantation

In Summary Optimize hemodynamic loading conditions to improve renal perfusion and function first. Optimize diuretic and medical therapy Using ACEi/ARBs and spironolactone often proves to be challenging in such patients. Avoid digoxin in such patients. Consider hydralazine and nitrates as a viable alternative. Hemodialysis/Ultrafiltration may be an option in a select population of patients to optimize loading conditions

Questions…?

What matters? Quality of Life / Prognosis Cost Need to balance the suffocating feeling of dyspnea with the inconvenience of dialysis Palliation / Supportive Care Cost Hope to save money by reducing hospitalizations Other more costly treatments that we provide