Left Ventricular Assist Devices for Lifelong Support

Dr Siva Subramaniyan

PGIMER &Dr.RML Hospital

New Delhi

INTRODUCTION

Heart disease is the leading cause of death in the Western world

~5 million people in the US have congestive heart failure (CHF)

250,000 are in the most advanced stage of CHF

~500,000 new cases each year

~50,000 deaths each year

only effective treatment for end stage CHF is heart transplant

stage D heart failure

• Despite the progress made in treating chronic systolic heart failure (HF), there remains a need for the contemporary approach to the management of advanced (stage D) HF to further evolve.

• For the past 3 decades, heart transplantation has been the established therapy of choice for the roughly 2,200 people per year who possess the appropriate age and freedom from significant comorbidity to be matched with a suitable donor .

• These individuals represent only a small fraction of the estimated 150,000 to 200,000 patients with stage D HF who endure a high symptom burden of shortness of breath, congestion, and fatigue despite maximally tolerated medication

ACCF/AHA guideline for the management of heart failure: a report of the ACC Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239

• It is for the larger group of individuals who face a high risk of short-term mortality and little chance of receiving a transplant that the emergence of continuous-flow (CF) left ventricular assist devices (LVADs) holds the greatest promise.

• These small implantable devices are capable of augmenting the circulation to meet the body’s physiological needs, both at rest and with exercise, extending survival and improving quality of life

ACCF/AHA guideline for the management of heart failure: a report of the ACC Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239

• One-year survival with current continuous-flow devices is reported to be 80%, and 2-year survival, 70%.

• In patients awaiting heart transplantation, MCS provides a bridge to transplantation, and for others who are ineligible for heart transplantation, MCS provides permanent support or destination therapy.

Interagency Registry for Mechanically Assisted Circulatory Support (INTER- MACS)

INTERMACS

VAD

• Classification of Ventricular Assist Devices

On the basis of period of use:

a) Temporary, b) Permanent

On the basis of impaired ventricle:

a) LVAD, b) RVAD, c) Bi-VAD

On the basis of Pumping mechanism:

a) Pulsatile b) Non pulsatile

Krishnamani, R. et al. (2010) Emerging ventricular assist devices for long-term cardiac support Nat. Rev. Cardiol. doi:10.1038/nrcardio.2009.222

DESTINATION THERAPY

• Currently in the United States, the most frequently used durable devices are

continuous- flow devices with axial (HeartMate II, St. Jude Corp, Minneapolis, MN) or

centrifugal - (HeartWare Ventricular Assist System, HeartWare Corp, Framingham, MA) flow

HeartMate II and HeartWare VAD

DEVICE COMPONENT

1.The pump

2.The driveline

3.The controller

4.The batteries

PUMP

The pump is internal. It is connected toleft ventricle that pulls blood into thepump which then sends the blood tothe ascending aorta

DRIVELINE

The driveline is internal and external. It is a tube that connects the pump to the controller. It contains necessary power and electronic cables. It exits through the skin, on either the right or left side of the abdomen

CONTROLLER

• Is external and it operates the pump and has lights, messages, and/or alarms if the power is low or if it is not functioning properly. It can be worn around the waist or over the shoulder.

BATTERIES

Options for Power

• Batteries

• AC power sources

HEARTMATE II VS HEARTWARE VAD

INDICATION

INTERMACS SCOREInteragency Registry for Mechanically Assisted Circulatory Support

Long-Term LVADIdeal candidates are INTERMACS classes 3-4

Short-Term LVADCandidates are INTERMACS classes 1-2

Not a LVAD CandidateINTERMACS 1 or those with multisystem organ failure

OPTIMIZING HEMODYNAMICS AND FLOW

• On the device controller, a display reports parameters that can be considered device “vital signs.” These include the speed (revolutions per minute), power (Watts), and flow (liters per minute;

• The HeartMate II device displays an additional pulsatility index parameter, which reflects the change in device flow over the cardiac cycle.

• Using a combination of CVP and PCWP, there are 5 patient profile possible:

1) normal resting hemodynamics (CVP 3 to 12 mm Hg, PCWP 8 to 18 mm Hg);

2) Rightsided HF (elevated CVP, normal PCWP);

3) Biventricular failure/fluid overload (elevated CVP and PCWP);

4) left-sided HF (normal CVP, elevated PCWP); and

5) hypovolemia (low CVP and PCWP)

• Only 40% to 60% of patients had “normal” hemodynamics (CVP <12 mm Hg and PCWP <18 mm Hg) at their set speed.

• a patient with a left-sided HF profile would likely benefit from a pump speed increase.

• Those with congestion or biventricular failure are likely best served by increased volume removal with augmented diuretic therapy.

• Lastly, hypovolemia benefitted from volume replacement

• Current clinical guidelines support the use of an echocardiographic ramp test to set pump speed .

• During such a test, pump speed is increased by a series of fixed increments over a set period of time to determine the degree of volume unloading defined by septal positioning, the presence and severity of mitral regurgitation, the frequency of aortic valve opening, and changes in the LV end-diastolic diameter (LVEDD) in the parasternal long-axis view.

COMANAGEMENT OF THE STABLE PATIENT

COMANAGEMENT OF THE STABLE PATIENT

• Longitudinal care of patients with MCS requires a multidisciplinary team to manage comorbid conditions.

• The implanting center typically maintains close follow-up; however, referring physicians and other specialty providers (often in outlying locations) participate in the coordinated plan of care

RETURNING TO NORMALCY

• Many signs and symptoms of heart failure (eg, shortness of breath, paroxysmal nocturnal dyspnea, and fluid weight gain) abate fairly soon after surgery.

• Other symptoms may resolve over a longer period of time (eg, fatigue, poor energy level, and decreased strength).

• Thus, early mobilization and rehabilitation are important to a successful recovery. Aggressive physical and occupational therapy should begin as soon as possible after MCS surgery, and cardiac rehabilitation should continue beyond hospital discharge

• MCS self-care

• Family caregiver support is an important component of selfcare

• patients with MCS adjust to performing activities of daily living (eg, bathing, dressing, sleeping, home management, and work) and engaging in leisure activities

• Driving is allowed

ANTICOAGULATION

• Anticoagulation with warfarin is required for all continuous- flow devices.

• however, the level of anticoagulation may vary by center, practice, and device type.

• Antiplatelet therapy with aspirin and often a second antiplatelet agent is necessary because of the threat of stasis, thrombosis, shear-induced platelet dysfunction, and hemolysis.

• Upregulation of platelet function is described with MCS and may contribute to long-term risk of thromboembolic events.

HYPERTENSION AND HYPOTENSION

• Titration of medical therapy to maintain a mean arterial blood pressure in the normal range is imperative to optimize forward flow and to prevent adverse events.

• Hypertension after ventricular assist device (VAD) implantation is common, and an increase in diastolic pressure with a continuous-flow device may exacerbate or lead to hypertension.

• Increased afterload decreases pump flow and increases the risk of neurological events and end-organ damage.

• Neurohormone-modifying agents such as ACEI, ARBs, β-blockers, and mineralocorticoid receptor antagonists are used to decrease afterload, to improve pump function, and to potentially contribute to ventricular recovery

RENAL FAILURE

• Renal insufficiency is common in end-stage heart failure. After MCS implantation, 67% of patients have been reported to experience improved renal function.

• while a minority experience AKI. AKI in the postoperative period is known to be a negative predictor of outcomes after PF-LVAD implantation and has been associated with an increased 1-year mortality in CF-LVAD recipients (relative risk 3)

causes of RF

• acute blood loss,

• volume shifts,

• arrhythmias, and

• the effect of multiple vasoactive medications influence renal hemodynamics.

The sudden change in renal blood flow characteristics due to LVAD support can lead to AKI .

Patients with preoperative RV failure and patients with INTERMACS scores of 1 or 2 are at higher risk of AKI

• Continuous veno-venous hemodialysis and inpatient intermittent hemodialysisare relatively common in the early postoperative recovery period.

MANAGEMENT OF CHRONIC COMPLICATIONS

RV Failure

• First, elevated preload from volume overload or blood resuscitation, for example, increases wall stress and can lead to RV dilation and functional tricuspid regurgitation.

• Second, high device speeds can lead to high CO, which may cause increased venous return to the failing RV.

• Third, an underfilled LV may allow shifting or suction of the interventricular septum. In this case, the loss of septal contribution to RV contractility can lead to RV failure.

• Finally, increased RV afterload attributable to pulmonary hypertension and elevated transpulmonary gradient is a common cause of RV failure.

• Transthoracic echocardiography may demonstrate RV dilation, hypocontractility, and septal shifting toward the LV.

• Inotropes to support RV function, pulmonary vasodilators to decrease transpulmonary gradient, or diuresis can be used in the short term to help the impaired and failing RV.

• If increased LV filling pressures are suspected (findings of hypertension or pulmonary edema), afterload reduction may improve RV function by augmenting forward flow.

• Phosphodiesterase type 5 inhibitors can be used in this setting to reduce pulmonary hypertension and to support the RV

AORTIC INSUFFICIENCY

• Aortic insufficiency is known to complicate ≈25% of patients with nonpulsatileMCS. The understanding of aortic insufficiency after MCS is evolving; however, continuous closure of the aortic valve is thought to be a central factor.

• Careful attention to outflow cannula orientation to prevent direct flow toward the aortic valve can minimize stress on the valve.

• For patients requiring long duration of support, aortic insufficiency may become a serious morbidity.

• Management of hypertension and intravascular volume optimization is important. If aortic insufficiency persists when these factors are controlled, further evaluation by the MCS center is necessary.

BLEEDING

• With continuous-flow devices, bleeding complications appear to be associated with additional factors beyond the level of anticoagulation.

• Factors contributing to bleeding include platelet dysfunction, acquired von Willebrand syndrome, and gastrointestinal bleeding related to arteriovenous malformations.

• Events most commonly seen are gastrointestinal bleeds and epistaxis

• The mechanism by which these AVMs develop is not entirely certain but is thought to be directly related to the lack of pulsatile blood flow, increased shear, and oxidative stress at a microvascular level

MANAGEMENT

• Treatment of mucosal bleeding is mostly supportive.

• Management guidelines provide some instruction regarding the withholding and gradual reintroduction of anticoagulation .

• Specific therapies targeting AVMs with octreotide or thalidomide have produced some anecdotal success

HEMOLYSIS

• A baseline level of hemolysis occurs in patients with MCS and may be monitored by periodic laboratory studies (eg, urinalysis, plasma free hemoglobin, haptoglobin, and lactate dehydrogenase analysis).

• Baseline and serial measurements are helpful after changes in clinical status when obstruction or thrombosis is considered.

• Elevation of lactate dehydrogenase above the patient’s baseline or 2.5 times the upper level of normal requires evaluation at an MCS center

PUMP THROMBOSIS

• Thrombosis is a relatively frequent adverse event, with a reported incidence of 5.5% to 12.2% in patients with MCS.

• Thrombosis is associated with significant morbidity because device exchange is typically necessary.

• INTERMACS data indicate that 2-year survival after pump exchange or no history of thrombus is 56% and 69%, respectively.

• Factors that may contribute to thrombus formation are subtherapeuticanticoagulation, low pump speed, and elevated blood pressure.

NEUROLOGICAL EVENTS

• Stroke is a relatively frequent adverse event of MCS.

• Among all devices, an incidence of 11% is observed at 1 year and of 17% at 2 years.

• Risk factors for stroke in patients on left VAD support remain poorly defined. Because hypertension is a known major risk factor for ischemic and hemorrhagicstroke, postimplantation hypertension should be avoided

INFECTION

• Infection remains one of the most common causes of morbidity and mortality during VAD support.

• Currently, the incidence of device infection is roughly 30% at 3 years. The percutaneous lead exit site through the skin poses risk for infection,

• trauma is the leading cause because a break in the healing seal formed at the driveline exit site provides a portal for infection.

• Patients and their families are trained in the immobilization of the percutaneous lead, meticulous exit-site care, and the prevention of pulling or dropping the external device components to minimize device infections

• The obligatory need for long-term antimicrobial therapy in such cases can lead to the emergence of drug-resistant organisms, especially in biofilm producing organisms such as Pseudomonas and Staphylococcus aureus

how effective is VAD?

SURVIVAL

survival depends in intermac score

INFECTION

FREEDOM FROM FIRST READMISSION

SUMMARY –INTERMACS

complications of VAD

Is it BIOCOMPATIBLE? MOMENTUM 3 trail

• biocompatibility refers to the ability of an implantable device to function without perturbing the body’s homeostatic systems

• The HeartMate 3 (Abbott, Inc.) is a next-generation centrifugal flow pump designed to be more biocompatible and to reduce AEs

MOMENTUM 3

• The study met its pre-specified superiority threshold, driven primarily by the infrequent need to replace the HeartMate 3 because of pump thrombosis.

• There were no significant differences between these 2 pumps with regard to stroke, bleeding, right-sided HF, functional capacity, or QOL.

• Results from the short-term cohort have been presented and published . The study’s primary endpoint, survival free of disabling or reoperation to replace or remove the pump, was met by 86.2% of HeartMate 3 patients compared with 76.6% in the HeartMate II group (p 0.037).

• The study met its pre-specified superiority threshold, driven primarily by the infrequent need to replace the HeartMate 3 because of pump thrombosis. There were no significant differences between these 2 pumps with regard to stroke, bleeding, right-sided HF, functional capacity, or QOL.

• At this point in time, it is premature to say that the HeartMate 3 is a fully hemocompatible pump, but the absence of suspected or confirmed pump thrombosis, at least in a short-term cohort, represents a significant incremental advancement in the field

INNOVATIVE SURGICAL TO MINIMIZE COMPLICATION AND IMPROVE THE OUTCOME IN LVAD

INNOVATIVE SURGICAL APPROACHES

• LVAD implantation surgery was previously one of the most morbid operations in cardiac surgery, with very high mortality and morbidity. In the REMATCH trial the hospital mortality rate for patients having a DT LVAD was 29%, the major perioperative bleeding rate was 46%, and the median hospital stay post-LVAD implantation was 29 days .

• The surgical results have since improved substantially, and a recent study of non–inotrope-dependent DT patients reported an operative mortality of 1% and a median hospital stay of 17 days.

• Although the basic surgical principles for implantation of all LVADs have remained constant over the past 3 decades, there are some notable modifications in surgical approach over recent years that deserve special mention.

LESS INVASIVE IMPLANTATION TECHNIQUES.

• Two Incision instead of sternotomy - 1 to gain access to the LV apex (usually a small left thoracotomy or a subcostal incision), and 1 to access the ascending aorta (usually a right minithoracotomy or an upper hemisternotomy)

• preliminary reports suggest a particularly low incidence of RV failure, bleeding complications, and respiratory failure with nonsternotomy approaches

REPAIR OF THE NATIVE HEART

• MS, moderate or severe AR, ASD

• Tricuspid annuloplasty

• CABG

• Stem cell ??

MYOCARDIAL RECOVERY IS POSSIBLE?

THE POTENTIAL FOR MYOCARDIAL RECOVERY

• Clinical observations have demonstrated that patients treated with high-dose neurohormonal antagonism–directed drugs or use of adjunctive cardiac resynchronization therapy exhibit reverse remodeling, sometimes with a marked improvement in cardiac structure and function.

• However, myocardial dysfunction in advanced-stage HF in patients who require mechanical circulatory support that leads to spontaneous recovery, which allows device explantation, is unusual, except in special reversible circumstances, such as patients with acute myocarditis, peripartum cardiomyopathy, and toxic cardiomyopathies.

• Several retrospective case series reported recovery, but it was only a decade ago that a prospectively designed protocol to achieve myocardial recovery in patients with advanced HF with nonischemic cardiomyopathy treated with a pulsatile LVAD was introduced

• The Harefield strategy included a staged approach, beginning with optimizing medical therapy using high doses of neurohormonal therapy, as well as digoxin (25 mg of carvedilol 3 times daily, digoxin 0.125 mg/day, lisinopril 40 mg/day, losartan 150 mg/day, and spironolactone 25 mg/day).

• These patients were then followed up for improvement in LV dimensions, and if normalization “on and off” (15 min with transient discontinuation) device support was noted, they transitioned into the next stage.

• At this stage, the nonselective b-blocker was transitioned to a b1-selective blocker, and clenbuterol, a selective b2-agonist, was also added to facilitate physiological hypertrophy.

• In this 15-patient series, 11 patients (73%) with nonischemic cardiomyopathy supported by a first-generation pulsatile HeartMate LVAD were able to undergo device explantation after an average support time of nearly 1 year. Freedom from recurrent HF at 1 and 4 years was 100% and 88.9%, respectively, in these selected patients.

ACHIEVING COST-EFFECTIVENESS

• Although improvements in pump technology, medical management, and insurance coverage expansion have allowed for increased utilization, the costs associated with LVAD use remain high

• Initial reports have estimated an incremental cost-effectiveness ratio (ICER) at 5 years of close to $220,000 per quality-adjusted life-year (QALY) for inotrope dependent recipients of LVADs compared with those who are medically managed.

• Cost reductions for device implantation, improvements in long-term survival, and greater patient functional status have made CF-LVADs more cost-effective

• But the major cost drivers were the need for frequent hospital readmission and the high costs of outpatient care distributed over a longer survival period.

• Therefore, even though the survival advantage of LVAD therapy is clear, further reductions in AEs, as well as improvements in QOL, are needed to meet conventional cost-effectiveness thresholds

CONCLUSION

• Continuous-flow LVADs have revolutionized advanced heart failure care.

• These compact, fully implantable heart pumps are capable of providing meaningful increases in survival, functional capacity, and quality of life.

• Implantation volumes continue to grow, but several challenges remain to be overcome before LVADs will be considered as the therapy of choice for all patients with advanced heart failure.

• They must be able to consistently extend survival for the long term (7 to 10 years), rather than the midterm (3 to 5 years) more typical of contemporary devices;

• They must incorporate design elements that reduce shear stress and avoid stasis to reduce the frequent adverse events of bleeding, stroke, and pump thrombosis and they must become more cost-effective.

• Now the focus on developing a more biocompatible device is translating into meaningful clinical benefit, with improved durability and fewer AEs

• advances in QOL will come with a fully implantable device without need for an external driveline, which will reduce infection risk and allow patients to swim and bathe. All of these advances are within sight and point toward a bright future for patients with advanced HF