The 10 million people worldwide with heart failure face a battle against a progressive disease characterised by deteriorating cardiac function that will rob them of their mobility and independence. More than a third of these individuals, 3.4 million, suffer from chronic heart failure, which dramatically affects their quality of life. Their prognosis for survival is poor and as many as 40–60% of these patients will die within a year.
An estimated 2 million of these people with chronic heart failure remain symptomatic despite optimal medical management and currently have no treatment options. They must simply wait for their disease to worsen to the point they are sick enough to potentially become eligible to receive one of the scarcely available transplant donor hearts.
Alternately, they may become too sick for a heart transplant or are ineligible, and progress to end-stage heart failure, requiring an emergency ventricular assist device (VAD) as a life-saving, but highly risky, procedure. The sobering reality is that while there are no other treatment options today to slow or halt the progression of chronic heart failure for millions of patients, the prevalence of chronic heart failure is nonetheless increasing worldwide.
This trend is likely to continue with the ageing of the population and the rise in prevalence of obesity, heart disease and diabetes. However, a new treatment option is in development to allow earlier intervention in the downward spiral of chronic heart failure. This group of patients is typically ambulatory and able to live at home, but experiences compromised quality of life and no longer responds to conventional optimal medical therapy. Even a modest improvement in circulatory capacity
could have a dramatic impact on their quality of life and potentially prevent end-stage heart failure.
Partial circulatory support
One solution to the management of patients with chronic heart failure may be the use of a continuous flow micro-pump device that alleviates the burden of patients' failing hearts. By supplementing the pumping power of the heart, a partial circulatory support device would allow the heart to rest and return it towards its normal state.
The circulatory assist devices currently available, grouped under the classification of full-support ventricular assist devices (VADs) are used in patients with insufficient cardiac output (1–2l/minute) and are designed to fully replace left ventricular function by pumping 5–6l or more of blood per minute. Alternately, a partial circulatory support device is designed for patients with 2–3l/minute of cardiac output and would supplement this by providing up to 3l/minute of blood flow to increase the total cardiac output.
VADs represent the last hope for dying patients with end-stage heart disease. VAD placement requires major surgery, including a sternotomy and cardio-pulmonary bypass, which carry a high risk of complications. The intra-operative risk and morbidity and mortality associated with full-support VADs is high, and these procedures are most often reserved as life-saving therapy in end-stage, Class IV patients.
In contrast, a partial circulatory support device offers several unique advantages. The device could be substantially smaller, simplifying placement and posing a smaller burden on patients. The potential for superficial and minimally invasive elective implantation of the device would greatly reduce the risks associated with surgery and promote more rapid patient recovery.
A partial circulatory support system not only addresses the treatment gaps left by VADs, but also by cardiac resynchronisation therapy (CRT). When patients progress to Class IIIb and early Class IV heart failure, optimal medical therapy and CRT are often insufficient in controlling the symptoms associated with even minimal physical exertion. These patients are also not yet candidates for a full-support VAD or heart transplant because they retain a resting cardiac output of over 2.5l/minute. This treatment gap is where partial circulatory support devices can play a critical role in actively unloading the heart and increasing total cardiac output.
Implanting such a device using a minimally invasive procedure, or even endovascular placement, would enable implantation without the need for sternotomy or cardio-pulmonary bypass. Innovative device design and refined implantation procedures would allow interventionalists to insert the devices using transcatheter techniques.
Synergy with the failing heart
CircuLite, Inc.'s Synergy™ Pocket Circulatory Assist device is the smallest implantable micro-blood pump for partial circulatory support and is the first partial circulatory support device to enter clinical evaluation. Smaller than an AA battery and weighing only 25g, it is tiny enough to be implanted superficially in a pacemaker-like pocket under the skin.
Capable of pumping up to 3l of blood per minute and of being electively implanted without the need for cardiopulmonary bypass or sternotomy, Synergy represents a potential new therapeutic option for patients who fall within the gap in the treatment continuum between responsiveness to medical therapy and CRT and the need for life-saving measures.
Synergy has completed extensive pre-clinical studies and began a First-in-Man clinical trial in Europe in 2007. The results of Synergy implantation in the first four study patients were positive and dramatic. All four patients experienced clinical hemodynamic improvement and shared similar outcomes, including rapid post-op recovery, and no significant hemolysis. These positive outcomes supported the expansion of this trial to enroll up to 20 patients to support CE mark approval for long-term use of the Synergy micro-pump in earlier-stage chronic heart failure patients.
Synergy works in conjunction with the heart to increase total cardiac output, drawing blood from the left atrium and pumping it to the subclavian artery. The micro-pump is based on proprietary and patented technology developed at the Hemholtz Institute in Aachen, Germany, in collaboration with Katholieke Universiteit in Leuven, Belgium.
Several unique features of the design are intended to prolong the life of the micro-pump. It incorporates a hydrodynamically levitated and magnetically stabilised rotor. This enables the rotor and motor to be physically separated by fluid and magnetic coupling that transmits torque from the hermetically sealed motor to the blood immersed rotor, eliminating blood contact of the motor bearing.
The micro-pump features a patented self-washing flow path, which washes the rotor area to prolong the pump's working lifespan. The current design life goal of the micro-pump is two years. If a device exchange is required, the unique superficial placement of the device enables minimally invasive micro-pump exchanges in under 60 minutes.
In addition to the micro-pump, the Synergy system includes two other primary components: the attachment system, comprised of the inflow cannula and the outflow graft; and the power system, which consists of two wearable lithium polymer battery packs and a controller. The inflow cannula incorporates a titanium tip and a Dacron ring to promote healing and minimise tissue overgrowth. The outflow graft is made of ePFTE to facilitate tissue in-growth. A 3mm flexible percutaneous lead exits the
skin at the patient's abdominal area and connects the micro-pump to the controller.
Patients wear the controller module and the lightweight dual battery packs around their waists. Each battery weighs less than 1.5lb. The entire power system weighs 3.3lb. The dual battery pack is rechargeable and will power the system for approximately 18 to 20 hours.
The competitive landscape
Partial circulatory support alternatives to traditional full-support VADs represent an emerging market sector. Second- and third-generation VADs, such as the HeartMate II from Thoratec, VentrAssist from Ventracor and HVAD from Heartware, offer smaller sizes and improved reliability, but weigh up to 370g or as much as 14 times that of the Synergy system. Compared to VADs, smaller and more portable partial circulatory support devices offer the potential for improved patient mobility and for elective implantation using minimally invasive mini-thoracotomy procedures or endovascular approaches.
The Exeleras® device from Orqis Medical Corp. and the IV-VAD from Heartware are other implantable rotary pumps in early development. Exeleras is proposed to be a fully implantable device designed to provide continuous aortic flow augmentation (pumping 1–1.5l/minute) and is in preclinical testing. The IV-VAD features an axial pump design concept which is intended to be implanted via a catheter-based delivery system; it is currently in the early prototype stage. Synergy, the pioneer of partial circulatory support, is the only system in clinical use.
Heart therapy of the future
As the number of patients with chronic heart failure continues to trend upward and the number of donor hearts available for transplant declines, the paradigm for treatment of chronic heart failure is changing.
When used in combination with minimally invasive implantation procedures, partial circulatory support systems present a viable option for long-term circulatory support in patients with earlier-stage chronic heart failure.
The rapid recovery and promising outcomes reported in the first four patients to receive the Synergy circulatory support device, together with extensive preclinical evaluation, provide initial proof-of-concept that the Synergy system increases total cardiac output sufficiently to improve a patient's functional capacity and quality of life.
Adding the Synergy circulatory support device to the current best practices for patients with chronic heart failure, in combination with existing
heart failure treatment options, can enable optimal dosing of drugs that are proven to improve patients' hemodynamic status. A device such as Synergy may improve quality of life and shift the treatment of chronic heart failure in a new direction.