Ventricular Assist Devices as Bridges or Destination Therapy

General description of procedure, equipment, technique

Ventricular assist devices (VAD) can be used to support the left ventricle (LVAD), right ventricle (RVAD), or both ventricles (BiVAD). VAD were developed to support patients with circulatory failure with failing organ systems and/ or near death to sustain life until cardiac transplantation became feasible.

The refinement of the devices and the improvements in outcomes has led to the widespread use of LVAD to support patients with advanced heart failure indefinitely. A durable VAD is implanted by a cardiac surgeon via a sternotomy and has a percutaneous driveline or connection to provide power and control of the device. Current devices weigh 1 lb or less and can deliver up to 10 L of flow per minute. The HeartMate II (Thoratec Corp) is FDA approved for bridge to transplant and destination therapy. It is implanted by a sternotomy and is a continuous flow LVAD (Figure 1, Figure 2).

Figure 1.

Figure 2.

VADs do not have sealed batteries contained internally, hence the need for the driveline to provide electrical power; the potential for infection remains a limitation of VAD. All VADs require anticoagulation and antiplatelet therapy; bleeding and stroke are complications.

Indications and patient selection

Left ventricular assist devices (LVAD) are approved for two indications: bridge to transplant (BTT) and destination therapy (DT). The Food and Drug Administration (FDA) approves devices based upon these two indications.

Although not designated by Centers for Medicare and Medicaid Services (CMS), many patients fall into an undifferentiated category or “bridge to decision.” Essentially, a bridge to decision patient is quite ill with comorbidities that might preclude an immediate decision regarding transplant candidacy. With successful LVAD support, many patients improve and become eligible for cardiac transplantation consideration.

VAD BTT are considered for patients listed for cardiac transplantation that require hemodynamic support. Generally patients considered for VAD BTT are inotrope dependent and/or have cardiorenal limitations (hypotension and renal insufficiency), negating the use of neurohormonal antagonists.

Patients intolerant of ACE inhibitors and beta blockers are generally quite ill and referred for LVAD consideration. Patients with pulmonary hypertension may also be considered for an LVAD, which can fully unload the left ventricle and reduce the pulmonary artery pressure.

Patients with advanced heart failure considered for LVAD as DT are generally ineligible for cardiac transplantation due to age and or comorbidities. LVAD is a potentially life-sustaining therapy that will enhance the quality of life in patients otherwise unlikely to survive more than 6 to 12 months. In clinical trials, about 75% of patients were inotrope dependent. In properly selected patients, LVAD will prolong life and improve quality of life dramatically compared to medical therapy.

Patient selection is based upon standard criteria established by CMS and published guidelines. (http://www.ishlt.org/ContentDocuments/JHLT_Feb13_MCS_Guidelines.pdf)

For BTT:

• Approved for heart transplant by a local selection committee and active or planned UNOS (United Network of Organ Sharing) listing of patient.

• Suitability for cardiac transplantation is based upon functional limitation and is generally evaluated with a metabolic stress test and other variables to estimate risk.

• Brain natriuretic peptide level, frequent hospitalizations for heart failure, and Seattle Heart Failure Model score are commonly used to predict mortality and to guide suitability for listing for transplantation.

Stable outpatients are infrequently advised to consider LVAD BTT. An LVAD is often needed to sustain the patient’s life and end organ function until a heart donor is available. Examples include:

• Failing end organs with renal and hepatic dysfunction

• Inability to tolerate BB or ACE

• Often inotropic dependent

• Poor functional capacity and quality of life

• Frequent hospitalization for heart failure

Various risk scores have been developed to estimate the mortality rate before hospital discharge after LVAD implant. The HeartMate II risk score multivariate predictors of 90-day mortality include age, albumin, creatinine, international normalized ration (INR), and implanting center volume.

For DT:

• Per CMS definitions, the patient should be ineligible for heart transplant: often due to chronologic age and comorbid conditions. Typically, approximately 75% of patients are on continuous inotropes.

• NYHA class IV on maximal medical therapy for >60 to 90 days.

• Ejection fraction <25%

• Most with peak oxygen consumption <12 ml/kg/min.

The patient has the appropriate body size (≥1.5 m²) to support the LVAD implantation.

Use of INTERMACS levels guides patient selection http://www.uab.edu/intermacs/

Patients are assigned an INTERMACS level, 1-7, with a modifier for uncontrolled ventricular arrhythmias. INTERMACS level 1 patients, which are the sickest (“crash and burn”), also have the highest 30-day mortality after LVAD.

Most patients undergoing LVAD today are INTERMACS level 2 and 3, which indicates chronic inotropic support. Risk scores have been developed to examine, low/medium/high risk patients using common clinical variables that predict mortality in hospitals postoperation until discharge.

In general avoid critically ill patients with frank or impending renal, hepatic, or pulmonary failure due to elevated mortality rates. Patients with multiorgan failure are very high risk. Patients with severe heart failure, on a ventilator, with impending renal failure with elevated MELD scores and right heart failure are complex to care for and have increased mortality.

For patients in shock and or multiorgan failure, ECMO or a percutaneous VAD such as Tandem Heart or Impella may be used. A heart failure specialist will help determine whether the patient should go to the OR for heart transplant, versus LVAD, versus no surgical therapy due to risk.

Contraindications

Contraindications to LVAD therapy are complex and require consultation with a heart failure cardiologist and an experienced LVAD surgeon.

Key contraindications:

• Inability to provide informed consent

• Inability to receive prolonged anticoagulation and antiplatelet therapy

• ESRD requiring renal replacement therapy

• Other irreversible life-limiting disease (e.g., malignancy, advanced emphysema, cirrhosis with elevated MELD score)

• Cerebrovascular disease and increased risk of stroke based upon neurologic consultation

• Inability or refusal to receive blood products

• Inability to be educated regarding VAD operation and or be compliant with a complex medical regimen

• Prohibitive and irreversible right heart failure

• Prohibitive and irreversible pulmonary hypertension and elevated pulmonary vascular resistance

• Inability to be placed on cardiopulmonary bypass due to aortic calcification and or additional anatomic limitations

• Lack of support from family and others to comply with a complex treatment regimen

• Lack of resources (e.g., insurance) to provide for ongoing medical care including dressing changes and follow-up care after VAD implant

Details of how the procedure is performed

VAD implantation is performed by a cardiac surgeon using standardized surgical techniques. Most often a full incision median sternotomy is required.

The patient is placed on cardiopulmonary bypass and typically cannulated after the chest is opened. An apical core is removed from the left ventricle (LV) and the inflow cannula is inserted in the LV and sutured in place.

The outflow graft is an end to side anastomosis to the descending aorta. The VAD is placed in the chest or in the abdominal cavity, depending on the size of the VAD used. A driveline is tunneled and exits via the skin in the right or left lower quadrant. The batteries and controller are external to the body.

Interpretation of results

Recent published clinical trials and postmarket approval studies have clearly demonstrated the outcomes in patients implanted with VAD. Additionally, the INTERMACS registry contains outcomes from over 145 participating sites and over 9,200 subjects enrolled.

INTERMACS is a prospective registry that collects clinical data including follow-up early postoperation and every 6 months. Major outcomes, including death, explant, rehospitalization, and adverse events, are publicly reported at the website. Quality of life and level of function is also collected and reported.

BTT clinical trials typically require 6 months of follow-up and assess mortality, survival to transplant, explant, device failure, and major adverse events, including stroke, device failure, infection, and bleeding.

DT clinical trials typically require 24 months of follow-up and they assess mortality, explant, device failure, and major adverse events. A smaller percentage of patients in DT clinical trials receive a transplant, as inclusion criteria specifies that those enrolled are not eligible for heart transplantation.

The FDA requires postmarket approval studies such that a cohort of patients implanted after approval are followed and outcomes are compared to a reference group of patients implanted with a previously approved VAD. Typically the “control” group is obtained from the INTERMACS registry and postapproval trials are nonrandomized. These postapproval trials ensure that outcomes are equal or exceed the outcomes observed when the VAD was initially implanted in the context of a clinical trial.

Outcomes (applies only to therapeutic procedures)

Survival with VAD will be reviewed for BTT, DT clinical trials, and the INTERMAC registry.

Expected survival rate for patients with LVAD BTT at 6 months is approximately 90% and the 30-day survival rate is approximately 95%. Competing outcomes for patients implanted with the HeartMate II LVAD BTT in a postmarket approval study at 6 months were:

• 90% transplanted, recovery, or ongoing support

• 69% ongoing

• 20% transplanted

• 9% death

• 2% explanted/recovery

Expected survival with HeartMate II continuous flow LVAD DT at 12 months and 24 months are 68% and 58%, respectively.

Major adverse events include disabling stroke, and reoperation to repair or replace VAD.

In the HeartMate II DT trial, the following adverse events were observed with the continuous flow LVAD:

• Pump replacement 9%; 0.06 events/patient-year

• Ischemic and hemorrhagic stroke 18%; 0.13 events/patient-year

• LVAD thrombosis 4%; 0.02 events/patient-year

Current INTERMACS registry data for VAD continuous flow survival in a cohort of 5,436 patients:

• 80%: 12 months survival

• 70%: 24 months survival

• 59%: 36 months survival

• 47%: 48 months survival

The INTERMACS registry demonstrates that the majority of LVAD recipients have improved ability to perform usual activities of daily living as shown in the Figure 4. The HeartMate II experience has shown an increase in the 6-minute walk test of +156 meters, which is remarkable.

Patient self-reported measures including the Minnesota Living with Heart Failure and the Kansas City Cardiomyopathy Scores both favorably improved. Although survival, functional capacity, and quality of life improve challenges remain as many patients are readmitted to the hospital and suffer complications, including GI bleeding, infections, and heart failure (Figure 3, Figure 4).

Figure 3.

Figure 4.n

Alternative and/or additional procedures to consider

No alternatives to VAD therapy except cardiac transplantation or palliative care. Patients considered for VAD in general have very poor quality of life and expected mortality in excess of 30% at 12 months or higher.

The ACC/AHA heart failure guidelines suggest for stage D heart failure: cardiac transplantation, LVAD as BTT or DT, palliative inotropes, or hospice/palliative care. The projected mortality for heart failure patients on chronic inotropic therapy is approximately 50% at 6 months and over 90% at 1 year. In addition, only cardiac transplantation and VAD therapy can provide a remarkable improvement in functional capacity (improved 6-minute walk) and quality of life.

Complications and their management

Complications after VAD remain challenging. All patients require anticoagulation and antiplatelet agents. All devices have a percutaneous drive line to link the implanted pump with the power supply and the controller.

Major complications include:

• Ischemic and hemorrhagic stroke

• GI bleeding

• Infection

• Right heart failure

• Device malfunction

• Device thrombosis

The INTERMACS registry indicates the only 30% of patients are free of infection, bleeding, stroke, device malfunction, and death 12 months after device implant (Figure 5).

Figure 5.n

Infection: driveline infection is well controlled with mobilization of the drive line at the time of implant, patient education regarding dressing changes, and being careful to maintain the integrity of the driveline interface with the skin by immobilizing the driveline. Experienced centers report driveline infection rates of less than 5% to 10%. A serious driveline infection can spread and involve the pump pocket, often leading to bacteremia and the need for chronic antibiotic suppression. Rarely a device change or urgent transplant is required for uncontrolled pump pocket infection and bacteremia. Incision and drainage is uncommon but can be effective for recurrent infections.

GI Bleeding: 20% of continuous flow VAD patients experience bleeding that can be epistaxis, and upper or lower GI bleeding. There is a propensity for bleeding from AV malformations. This may be related to a relative lack of pulsatile flow. When transfusions are required, both aspirin and warfarin are stopped and an upper and lower endoscopy is performed for GI bleeding. A negative capsule endoscopy is sometimes required. Occasionally angiography and interventional radiology may be consulted to control bleeding. Patients with continuous flow LVAD may develop acquired reduction in Von Willebrand multimers and hence be at risk for bleeding.

Right heart failure: It is important to carefully select patients for LVAD expected to have improvement in right ventricular function. If a patient requires inotropic therapy to support RV function >14 days after LVAD implant, increased mortality is expected. A variety of risk scores to predict RV failure after LVAD have been developed. In general a patient with severe RV dysfunction assessed by echo, CVP >20 cm H₂0, and severe tricuspid regurgitation is of concern for RV failure. Alternatives are to consider BIVAD support or a total artificial heart. Patients that go back to the operating room for an RVAD have increased mortality. A small percentage of patients that have done well for many months will return with volume overload and poor RV function. An echo and right heart catheter should be performed to assess the severity of the hemodynamic abnormality and to determine if the RV failure can be ameliorated by additional unloading of the left ventricle. In general, most patients respond to intravenous diuretics. A small percentage may require chronic inotropic therapy in addition to the LVAD.

Device malfunction is rare. If alarms sound immediate, interrogation by a VAD coordinator is required. Very rarely a patient will require urgent surgery for pump replacement for a catastrophic device malfunction.

Device thrombosis: This is a spectrum usually characterized by hemolysis, abnormal pump function, inadequate unloading of the left ventricle, and clinical heart failure. The published clinical trials indicate this occurs in <5% to 10% of cases treated with adequate anticoagulation. If a patient presents with heart failure, check for hemolysis and request a VAD interrogation by the VAD coordinator.

If hemolysis and anemia are present, the VAD should be checked for alarms and the patient should be very carefully assessed for evidence of heart failure/inadequate unloading of the LV. Rarely device thrombosis will require urgent VAD replacement. Most cases are treated with heparin and intensified anticoagulation and improve.

Stroke is a devastating complication and can be ischemic or hemorrhagic. In general adequate anticoagulation is mandated to reduce the risk of VAD thrombosis and stroke. Hemorrhagic stroke is often fatal.

Any change in neurologic function is a medical emergency and requires immediate imaging of the brain and consultation with the stroke service. Anticoagulation is generally held until brain imaging is completed and evaluated. No specific VAD parameters need to be changed when stroke occurs.

Patients with known extensive cerebrovascular disease and or prior SAH may be at increased risk and should be carefully assessed by a neurologist before considering VAD therapy. Emerging data suggests that meticulous blood pressure control is also important to reduce the risk of stroke and that the mean arterial pressure (MAP) should be <85 mm Hg.

After prolonged VAD support (>18 months), the leaflets of the aortic valve may become fused and lead to the development of aortic insufficiency. Any VAD patient that has a change in their condition from a cardiac perspective should undergo a careful echo assessment.

What’s the evidence?

Miller, LW. “Use of a continuous-flow device in patients awaiting heart transplantation”. N Engl J Med,. vol. 357. 2007. pp. 885-96. (This report describes the pivotal clinical trial providing evidence for the U.S. FDA approval of the continuous flow LVAD as a bridge to transplant and demonstrates the advances compared to the pulsatile LVAD.)

Slaughter, MS, Rogers, JG, Milano, CA. “HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device”. N Engl J Med. vol. 361. 2009. pp. 2241-51. (This report describes the pivotal clinical trial providing evidence for the U.S. FDA approval of the continuous flow LVAD as chronic destination therapy and demonstrates the advances compared to the pulsatile LVAD.)

Rogers, JG. “Continuous flow left ventricular assist device improves functional capacity and quality of life of advanced heart failure patients”. J Am Coll Cardiol. vol. 55. 2010. pp. 1826-34. (This review describes the impressive improvements in NYHA class, quality of life, and 6-minute walk distance with the use of a continuous flow LVAD.)

Starling, RC. “Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)”. J Am Coll Cardiol. vol. 57. 2011. pp. 1890-8. (This report demonstrates that results with the continuous flow LVAD post-BTT approval after wide use are comparable or superior to outcomes in the pivotal clinical trial.)

Aaronson, KD. “Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation”. Circulation,. vol. 125. 2012. pp. 3191-200. (This report reviews the pivotal clinical trial comparing the HVAD (centrifugal pump) with the axial flow LVAD in a bridge to transplant clinical trial.)

Matthews, JC. “The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates”. J Am Coll Cardiol. vol. 51. 2008. pp. 2163-72. (Predicting adequate RV function post-LVAD is challenging; this study provides a risk assessment tool to assess the severity of RV function and outcomes post-LVAD.)

Kirklin, JK, Naftel, DC, Kormos, RL. “Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients”. J Heart Lung Transplant. vol. 32. 2013. pp. 141-56. (A wealth of LVAD information is contained in this INTERMACS report of the U.S. registry with over 6,000 implants.)

Cowger, J, Sundareswaran, K, Rogers, JG. “Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score”. J Am Coll Cardiol. vol. 61. 2013. pp. 313-21. (The derivation and validation of the HeartMate II Risk score is a valuable article to review to help in selection of patients for LVAD.)

Park, SJ, Milano, CA, Tatooles, AJ. “Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy”. Circ Heart Fail. vol. 5. 2012. pp. 241-8. (This report demonstrates that results with the continuous flow LVAD post-DT approval after wide use are comparable or superior to outcomes in the pivotal clinical trial in destination therapy patients.)

Russell, SD, Rogers, JG, Milano, CA. “Renal and hepatic function improve in advanced heart failure patients during continuous-flow support with the HeartMate II left ventricular assist device”. Circulation. vol. 120. 2009. pp. 2352-7. (This impressive article chronicle that end organ function will improve in critically ill patients successfully treated with continuous flow LVAD therapy.)

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