Dobutamaine Versus Milrinone in Cardiorenal Syndrome

Heart failure is recognized as one of the most common indications for hospitalization amongst adults aged \>65 years in United States with estimated Medicare cost to be 17 billion or more. Chronic heart failure is one of the most life threatening cardiovascular disorder thought to affect nearly six million US population with 600,000 new cases every year. The heart is responsible for perfusion to all vital organs including kidneys and dysfunction in either affects both the vital organs. When dysfunction of heart leads to dysfunction of kidneys or vice versa it is referred to as cardio renal syndrome (CRS). The underlying pathophysiology for CRS has been poorly understood and considered multifactorial. Worsening renal function defined as increase in serum creatinine of \>0.3mg/dl from baseline occurs in 20-30% of patients with ADHF and is associated with greater length of hospital stay, hospital readmission and death. A number of interventions have been used including giving diuretics which helps in decongestion and helps the heart pump blood more effectively. Sometimes these therapies are not effective and may even lead to worsening of renal function. In such cases , inotrope agents which increase the contractility of the heart have been used to help pump more blood to vital organs. There have been very few trials assessing the efficacy of these agents for improving kidney function .The investigators aim to assess the renal recovery with two such agents - dobutamine and milrinone in patients with cardiorenal syndrome who are coming with acute decompensated heart failure

Heart failure is recognized as one of the most common indications for hospitalization amongst adults aged \>65 years in United States with estimated Medicare cost to be 17billion or more. Chronic heart failure is one of the most life threatening cardiovascular disorder thought to affect nearly six million US population with annual death rate being 600,000. Cardiorenal syndrome although not completely understood in its full context - is a term coined for disorder of the heart and kidneys whereby acute or chronic dysfunction of one precipitates acute or chronic dysfunction of the other. Concomitant kidney failure amongst patients with acute decompensated heart failure is commonly observed . Direct and indirect effects of heart failure other than hemodynamic insult have been identified as primers for acute kidney injury and dysfunction. Patients with preexisting underlying renal disease are more likely to develop worsening renal failure in the setting of ADHF with venous congestion being the most important hemodynamic factor driving it. Worsening renal function defined as increase in serum creatinine of \>0.3mg/dl from baseline occurs in 20-30% of patients with ADHF and is associated with greater length of hospital stay, hospital readmission and death. The treatment of ADHF which includes the step up intravenous diuretic therapy in addition to optimizing baseline medicines is limited frequently by diuretic resistance and worsening creatinine level precluding use of Angiotensin converting enzyme inhibitors (ACEi), Angiotensin Receptor Blocking Agents (ARBs), and Spironolactone. Ultrafiltration/Aquapheresis still remains an option for treating non-responders to medical therapy. Inotropes have been known to produce a beneficial hemodynamic effect on heart and lead to better titration to oral regimen. Short term continous intravenous infusion of inotropic agents in patients with documented severe systolic dysfunction who present with significantly depressed cardiac output to maintain end organ perfusion has been shown to be beneficial as per the ACC/AHA guidelines 2013 for management of heart failure. The use of intravenous inotropes remains still a controversial topic in terms of its short lived and long term efficacy on renal recovery in acute decompensated heart failure. In view of the large proportion of patients admitted with acute decompensated heart failure and no real world studies comparing different inotropes to improve kidney function, the investigators aim to compare the efficacy of dobutamine and milrinone in improving kidney function and also their effect on length of stay, symptomatic improvement and medication optimisation

1. The primary objective of the study is to objectively measure the response of dobutamine vs milrinone for renal recovery in patients with cardiorenal syndrome (\>0.3mg/dl increase in creatinine from baseline) admitted for acute decompensated heart failure. These objective measures include change in serum creatinine, change in weight.
2. The secondary objectives are to measure the length of hospitalization, readmission rates and unscheduled visits to the clinic or ER during 60 day follow up period. The investigators will also measure changes in symptoms which will be assessed using global and dyspnea visual analog scale every 24 hours until the patient is discharged .
3. The secondary objectives also include to measure diuretic dose, medicine optimization including initiation of beta blocker / ace inhibitors before discharge, at 30 days and 60 days interval
4. The investigators will subdivide the patients into ischemic versus non ischemic at the end of trial to see the response in both these categories of patients

Eligibility Criteria:
Inclusion Criteria:

1. Age \>18 years
2. Admitted to the hospital with a primary diagnosis of Decompensated Heart Failure
3. Onset of cardio-renal syndrome (increasing creatinine\>0.3mg/dl) after or before hospitalization. After hospitalization within 7 days of from the time of admission after receiving intravenous diuretics and heart failure medication optimization. Before hospitalization in the setting of escalating doses of outpatient loop diuretics and heart failure medication optimization
4. Persistent volume overload- For patients with a pulmonary artery catheter, peristent volume overload will include :

   Pulmonary capillary wedge pressure \>22mm Hg and one of the following clinical signs :2+ peripheral edema and/or pulmonary edema or pleural effusion on chest Xray. For patients without a pulmonary artery catheter- persistent volume overload will include atleast 2 of the following: 2+ peripheral edema , jugular venous pressure \>10 mm Hg and pulmonary edema or pleural effusion on chest Xray
5. BNP\>400
6. Cr-1.2-3.0

Exclusion Criteria:

1. Intravascular volume depletion
2. Acute coronary syndrome within 4 weeks
3. Indication for hemodialysis
4. Systolic Blood pressure \<90mm Hg or MAP\<60mm Hg at the time of enrollment
5. Alternate explanation for worsening renal function , such as obstructive nephropathy , contrast induced nephropathy , ATN
6. Clinical instability likely to require the addition of intravenous vasoactive drugs including vasodilators and/or inotropic drugs
7. The use of iodinated radio-contrast material in the past 72 hours or anticipated use of intravenous contrast during the current hospitalization
8. Underlying rhythm disorder