Systems and methods for controlling renovascular perfusion

The present application is a continuation of U.S. patent application Ser. No. 10/453,678, filed Jun. 2, 2003, which is a divisional of U.S. patent application Ser. No. 09/702,089, filed Oct. 30, 2000, the full disclosure of which is incorporated herein by reference.

The present invention generally relates to medical devices and methods of use for the treatment and/or management of cardiovascular and renal disorders. Specifically, the present invention relates to devices and methods for controlling renal perfusion in the renovascular system for the treatment and/or management of cardiovascular disorders such as hypertension and congestive heart failure, and renal disorders such as renal insufficiency and end stage renal disease.

Cardiovascular disease is a major contributor to patient illness and mortality. It also is a primary driver of health care expenditure, costing more than $326 billion each year in the United States. Hypertension, or high blood pressure, is a major cardiovascular disorder that is estimated to affect over 50 million people in the United States alone. Of those with hypertension, it is reported that fewer than 30% have their blood pressure under control. Hypertension is a leading cause of heart failure and stroke. It is the primary cause of death in over 42,000 patients per year and is listed as a primary or contributing cause of death in over 200,000 patients per year in the U.S. Accordingly, hypertension is a serious health problem demanding significant research and development for the treatment thereof.

Hypertension occurs when the body\'s smaller blood vessels (arterioles) constrict, causing an increase in blood pressure. Because the blood vessels constrict, the heart must work harder to maintain blood flow at the higher pressures. Although the body may tolerate short periods of increased blood pressure, sustained hypertension may eventually result in damage to multiple body organs, including the kidneys, brain, eyes and other tissues, causing a variety of maladies associated therewith. The elevated blood pressure may also damage the lining of the blood vessels, accelerating the process of atherosclerosis and increasing the likelihood that a blood clot may develop. This could lead to a heart attack and/or stroke. Sustained high blood pressure may eventually result in an enlarged and damaged heart (hypertrophy), which may lead to heart failure.

Heart failure is the final common expression of a variety of cardiovascular disorders, including ischemic heart disease. It is characterized by an inability of the heart to pump enough blood to meet the body\'s needs and results in fatigue, reduced exercise capacity and poor survival. It is estimated that approximately 5,000,000 people in the United States suffer from heart failure, directly leading to 39,000 deaths per year and contributing to another 225,000 deaths per year. It is also estimated that greater than 400,000 new cases of heart failure are diagnosed each year. Heart failure accounts for over 900,000 hospital admissions annually, and it is the most common discharge diagnosis in patients over the age of 65 years. It has been reported that the cost of treating heart failure in the United States exceeds $20 billion annually. Accordingly, heart failure is also a serious health problem demanding significant research and development for the treatment and/or management thereof.

End stage renal disease (ESRD) affects over 300,000 people in the United States, with an annual incidence of over 79,000. Death from ESRD occurred in over 60,000 cases in 1998; the five year survival rate is less than 30%. Medicare payments in 1998 for the treatment of ESRD exceeded $10 billion. Accordingly, ESRD is a major health problem demanding improved therapy and management.

Heart failure results in the activation of a number of body systems to compensate for the heart\'s inability to pump sufficient blood. Many of these responses are mediated by an increase in the level of activation of the sympathetic nervous system as well as activation of multiple other neurohormonal responses. Generally speaking, this sympathetic nervous system activation signals the heart to increase heart rate and force of contraction to increase the cardiac output; it signals the kidneys to expand the blood volume by retaining sodium and water; and it signals the arterioles to constrict to elevate to the blood pressure. The cardiac, renal and vascular responses increase the workload of the heart, further accelerating myocardial damage and exacerbating the heart failure state. Accordingly, it is desirable to reduce the level of sympathetic nervous system and other neurohormonal activation in order to stop or at least minimize this vicious cycle and thereby treat or manage the heart failure.

A number of drug treatments have been proposed for the management of hypertension, heart failure and other cardiovascular and renal disorders. These include vasodilators to reduce the blood pressure and ease the workload of the heart, diuretics to reduce fluid overload, inhibitors and blocking agents of the body\'s neurohormonal responses, and other medicaments.

Various surgical procedures have also been proposed for these maladies. For example, heart transplantation has been proposed for patients who suffer from severe, refractory heart failure. Alternatively, an implantable medical device such as a ventricular assist device may be implanted in the chest to increase the pumping action of the heart. Alternatively, an intra aortic balloon pump may be used for maintaining heart function for short periods of time, but typically no longer than one month. Other surgical procedures are available as well.

Although each of these alternative approaches is beneficial in some ways, each of the therapies has its own disadvantages. For example, drug therapy is often incompletely effective. Some patients may be unresponsive (refractory) to medical therapy. Drugs often have unwanted side effects and may need to be given in complex regimens. These and other factors contribute to poor patient compliance with medical therapy. Drug therapy may also be expensive, adding to the health care costs associated with these disorders. Likewise, surgical approaches are very costly, may be associated with significant patient morbidity and mortality and may not alter the natural history of the disease. Accordingly, there continues to be a substantial and long felt need for new devices and methods for treating and/or managing high blood pressure, heart failure and renal disease, as well as their associated complications.

The present invention provides a number of devices, systems and methods by which the real or apparent renovascular perfusion and the renal interstitial hydrostatic pressure may be selectively and controllably increased. By selectively and controllably increasing renovascular perfusion and interstitial hydrostatic pressure when the heart is unable to pump sufficient blood or when renal perfusion is otherwise suboptimal, the renal system does not experience the reduced perfusion. Because the renal system does not experience the reduced perfusion, it does not initiate or contribute to, and may reduce the neurohormonal activation normally caused by reduced cardiac output and suboptimal renal perfusion, nor does it begin or continue, and could reverse the process of sodium and water retention that also would otherwise result. Thus, by selectively and controllably increasing renovascular perfusion during periods of decreased cardiac output or suboptimal renal perfusion, the present invention reduces or reverses neurohormonal activation and fluid retention, and thereby minimizes their deleterious effects on the heart, vasculature, kidneys and other body systems.

In the case of end stage renal disease (ESRD), the present invention provides a number of devices, systems and methods by which renal perfusion and pressure can be increased, thereby restoring or augmenting perfusion of the kidney and blood filtration. In addition, by increasing renal perfusion, the present invention increases interstitial pressure to reduce sodium and water reabsorption, which have been shown to be interrelated.

In an exemplary embodiment, the present invention provides a method of treating a patient utilizing a blood perfusion modification device, one or more physiologic sensors, and a control system. The blood perfusion modification device may be positioned in the renovascular circulation or immediately adjacent thereto. The sensor is preferably positioned in a renal artery or upstream thereof, but may also be placed in, on or adjacent the patient to generate a signal indicative of the need to modify renal perfusion. For example, the sensor may be positioned in a kidney, a renal artery or vein or adjacent thereto to generate a signal indicative of arterial blood perfusion, renal venous pressure or renal interstitial pressure. The blood perfusion modification device may be activated, deactivated or otherwise modified as a function of the sensor signal to cause or simulate a change, and preferably an increase, in renal perfusion and/or pressure. This method may be used to treat a number of clinical conditions including congestive heart failure, hypertension, renal failure, cardiovascular abnormalities, and the like. In each instance, the method may include the initial step of diagnosing or monitoring the clinical condition or a symptom or sign thereof, and thereafter providing treatment as needed.

The present invention also provides a system including a blood perfusion modification device (e.g., a flow regulator, a flow redirector or a pump), a physiologic sensor (e.g., a transducer or a gauge), and a control system operably connected to both. The blood perfusion modification device is preferably positioned in the renovascular circulation. The control system (or a portion thereof) may be implanted or carried externally by the patient. In the closed loop mode, the sensor generates a sensor signal indicative of the need to modify renovascular perfusion, and the control system generates a control signal to activate the modification device as a function of the sensor signal to thereby modify the renovascular circulation. In the open loop mode, which may or may not utilize feedback from the sensor, the control system generates a control signal to activate the modification device as dictated by, for example, a pre programmed algorithm, the patient or the physician.

The sensor may comprise, for example, a piezoelectric pressure transducer, an ultrasonic flow velocity transducer, a thermodilution flow transducer, or a strain gauge. As such, the sensor may generate a signal indicative of pressure (e.g., mean, systolic, diastolic or pulse), blood flow velocity, vasoactivity, or other fluid dynamic property. Alternatively, the sensor may measure the blood concentration of a component (e.g., sodium, renin, etc.) or an arterial/venous difference in concentration of the component.

The blood perfusion modification device may comprise a flow regulator positioned in a renal vein or immediately downstream thereof to create backpressure in the renovascular circulation. Alternatively, the blood perfusion modification device may comprise a flow redirector positioned downstream of a renal artery to redirect blood flow to the renal artery. As a further alternative, the blood perfusion modification device may comprise a pump. The pump may be positioned upstream of a renal artery to supplement blood flow to the renal artery or positioned downstream of a renal vein to supplement blood flow from the renal vein. As yet a further alternative, the blood perfusion modification device may comprise a drug delivery device. In each of these embodiments, the blood perfusion modification device may be positioned intravascularly or extravascularly. By way of example, not limitation, the blood perfusion modification device may comprise an inflatable cuff, a rotatable ring, a hydraulic piston, a solenoid, an inflatable balloon, or a drug delivery device.

The control system may include a processor and memory. The memory may include software containing one or more algorithms defining one or more functions or relationships between the control signal and the sensor signal. The algorithm may dictate activation or deactivation control signals depending on the sensor signal or a mathematical derivative thereof. The algorithm may dictate an activation or a deactivation control signal when the sensor signal falls below a lower predetermined threshold value, rises above an upper predetermined threshold value or when the sensor signal indicates a specific physiologic event.