In recent years, the University of Michigan Frankel Cardiovascular Center has played a key role in a flurry of research into treating heart failure. A number of ongoing studies at the university hope to add to available treatment options.
“The EXPAND trial is probably the most important trial we have ongoing now. It might transform the way we do heart transplantation in this country,” says Francis Pagani, M.D., Ph.D., a cardiac surgeon at the Frankel Cardiovascular Center.
“We are one of 12 centers participating in EXPAND,” he says. The trial is evaluating a new portable organ care system that perfuses the heart with oxygen and nutrients and keeps a donor heart functioning at normal body temperature while it is transported to a recipient. The trial is testing whether this method of maintaining the donor organ is superior to the current method of storing the heart on ice.
Center for LVAD Research
The MOMENTUM III trial, ongoing at 60 centers in the United States, is evaluating a new left ventricular assist device (LVAD) called HeartMate 3 (Thoratec). This implantable device circulates blood throughout the body when the heart is too weak to pump blood adequately on its own. Patients must have advanced heart failure that is refractory to current treatment to be eligible for the study. So far, 200 patients have been enrolled in the trial at the Frankel Cardiovascular Center.
The SynCardia Total Artificial Heart 50-cc trial is testing a smaller total artificial heart for use in women and smaller men. “One of the limitations with the artificial heart technology is that it is so large that it only fits in large-bodied people,” says Dr. Pagani, speaking about the 70-cc total artificial heart. “The 50-cc size of this model makes it more suitable for smaller-bodied individuals.”
The Cardiothoracic Surgical Trials Network Cell Therapy LVAD Trial II is examining whether injecting allogeneic stem cells into the heart during implantation of an LVAD can improve long-term myocardial function. “This is a significant trial that could give us important insights into the potential for stem cells to improve heart function in patients with advanced heart failure,” says Dr. Pagani.
Heart Failure Studies and Support
Scott Hummel, M.D., M.S., a cardiologist at the Frankel Cardiovascular Center, says his main area of interest is “diastolic,” or “preserved ejection fraction,” heart failure (HFpEF). “There are no broad evidence-based therapies for HFpEF yet, but we use exercise testing, imaging and sometimes catheterization to phenotype patients and direct treatment to the underlying mechanisms. We also lead several clinical studies that are looking at the importance of dietary modifications,” Dr. Hummel adds.
For example, the DASH-DHF 2 (Dietary Approaches to Stop Hypertension in 'Diastolic' Heart Failure 2) study is investigating how recommended dietary changes affect heart and blood vessel function in patients with hypertensive HFpEF.
The Frankel Cardiovascular Center has one of the largest inherited cardiomyopathy and arrhythmia programs in the United States, and provides comprehensive evaluation of patients and families, including risk assessment for sudden cardiac death, medical and surgical treatments, and genetic counseling. They also participate in several international multicenter registries and clinical trials focusing on lifestyle/exercise and new pharmacologic agents to prevent the development and/or progression of hypertrophic cardiomyopathy.
The University of Michigan is a founder and key participant in the Cardiac Sarcoidosis Consortium, an international registry of cardiac sarcoidosis that aims to improve medical decision making and outcomes of this systemic disease process. Patients with suspected or proven cardiac sarcoidosis are followed using a multidisciplinary approach to improve diagnosis, management and risk stratification for sudden cardiac death.
In addition to the expertise of heart failure specialist physicians, nurse practitioners and physician assistants, patients benefit from a team of nurse case managers whose sole responsibility is to manage patients with heart failure. “We are studying the best methods for patient telemonitoring across the spectrum of heart failure, including patients with LVADs,” notes Dr. Hummel.
Dr. Hummel says the Frankel Cardiovascular Center welcomes referrals from and collaboration with other practices. Referring physicians should consult the suggested guidelines for referral of advanced heart failure patients (see below).
“One of the biggest challenges that can happen is when someone is referred too late, when other organs in the body are failing besides the heart,” says Dr. Hummel. “Getting involved in a patient’s care when they are not yet critically ill is the best time to have conversations about what treatments are available.”
Guidelines for Referral for Advanced Heart Failure Therapy:
Ventricular Assist Device Therapy and/or Heart Transplantation
Patients should have:
- At least class III heart failure symptoms
- LVEF ≤35% (This guideline is not necessary for patients with “diastolic” or “preserved ejection fraction” heart failure that is due to restrictive cardiomyopathies, e.g., hypertrophic cardiomyopathy, sarcoidosis)
And any of the following criteria:
- Early end-stage organ dysfunction
- BUN ≥45 mg/dL
- Cr ≥1.6 mg/dL or CrCl ≤45 cc/min
- Serum sodium <135 mEq/L
- Hemodynamic instability
- Ventricular arrhythmias
- Low cardiac output
- Hospitalization for heart failure in the past 6 mo
- Intolerance/withdrawal of evidence-based heart failure oral agents
- Nonresponsive to CRT/BiV pacing
- Being considered for or currently on inotropes
- Cardiac cachexia
- High diuretic dose
- Furosemide ≥160 mg/d
- Torsemide ≥80 mg/d
- Bumetanide ≥4 mg/d
- Seattle Heart Failure score ≥1.5 or 1-y mortality estimate >15%
- Peak exercise oxygen consumption ≤55% of predicted or absolute number (≤14 mL/kg/min for women or ≤16 mL/kg/min for men)
- 6MWT (distance, ≤350 m)
Recommended Testing Before Evaluation (within 3 months):
- Abdominal ultrasound (to evaluate for AAA and hepatic disease)
- Ankle-brachial index test
- Carotid duplex scan
- Chemistries and complete blood count
- Chest radiograph
- Noncontrast CT scan of the thorax (if history of prior cardiac surgery)
- Peak VO2 and 6MWT distance (if available)
- Pulmonary function test
- Right heart catheterization (if available)
|6MWT||6-minute walk test|
|AAA||abdominal aortic aneurysm|
|BUN||blook urea nitrogen|
|CRT||cardia resynchronization therapy|
|LVEF||left ventricular ejection fraction|
|VO2||maximal oxgen consumption|
New Drugs Offer New Options
In the past year, two new drugs have been approved for heart failure:
Ivabradine (Corlanor, Amgen) was approved for patients who:
- have stable, symptomatic chronic heart failure with a left ventricular ejection fraction of 35% or less;
- are also in sinus rhythm with a resting heart rate of at least 70 beats per minute; and
- are either on maximally tolerated doses of β-blockers or have a contraindication to β-blocker use.
Sacubitril-valsartan (Entresto, Novartis) was approved for the treatment of chronic heart failure with reduced ejection fraction. The drug is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker already used to treat heart failure.
“In a large clinical trial, Entresto was compared to an angiotensin-converting enzyme inhibitor and found to reduce cardiovascular death and heart failure hospitalization by 20%. The results are undeniably impressive, and the drug may have a big impact on our patients,” says Scott Hummel, M.D., M.S. He notes that one challenge for clinicians is determining whether to use sacubitril-valsartan in patients who don’t meet the enrollment criteria that were used in the clinical trial; for example, those with low blood pressure or more than moderate chronic kidney disease.
Review a list of cardiovascular clinical studies at the University of Michigan Frankel Cardiovascular Center here.
To consult with a physician or refer a patient, call our 24/7 physician-to-physician connection, M-LINE, at 800-962-3555.