Dynamic Cardiomyoplasty

Decades in development, this procedure was introduced into clinical practice in 1985 by Carpentier and Chachques. In dynamic cardiomyoplasty, an electrically stimulated flap of skeletal muscle (e.g., latissimus dorsi) was wrapped around the heart in an attempt to augment systolic function. Between 1985 and 1991, approximately 185 dynamic cardiomyoplasties were performed worldwide in 17 countries. Although subjective improvement was widely reported by patients who had undergone the procedure, objective measurements of significant functional improvement were inconsistent.

Acorn CorCap Cardiac Support Device

The CorCap Cardiac Support Device (Acorn Cardiovascular, Inc., Minneapolis, MN) is an investigational mesh fabric that is surgically wrapped around the heart in an attempt to prevent further dilation. This device has been shown in animal models to reduce wall stress, myocyte hypertrophy, and myocardial fibrosis. A global multicenter study by Oz and coworkers⁹ showed promising results. There were significant reductions in LV end-diastolic dimensions, MR grade, and NYHA classification in patients 12 months after CorCap implantation. At the same time, a significant improvement was seen in LVEF and quality of life. Ongoing randomized clinical trials in Europe and the United States will further address the safety of implantation of the CorCap device and ultimate outcomes.

Currently Available Ventricular Assist Devices: Indications and the Basic Strategy of Their Use

Mechanical circulatory assistance with a VAD has become common management of intractable cardiogenic shock that follows cardiac surgery, myocardial infarction (MI), or severe viral myocarditis, as well as in the patient with end-stage cardiomyopathy awaiting transplantation. All currently available VADs are pumps that collect blood returning to the heart and eject it downstream of the failing ventricle. Effectively, they take over the pumping function of the failing ventricle and can provide adequate systemic perfusion to prevent the devastating sequelae of cardiogenic shock (e.g., multisystem organ failure). With the potential exception of centrifugal pumps, currently approved VADs do not provide oxygenation or removal of waste from the blood—they simply act as pumps that can maintain perfusion of the body in the place of a failing ventricle.

While the VAD is acting to maintain the circulation, decompression of the failing ventricle will decrease ventricular wall tension and therefore myocardial oxygen demand. To decompress the failing ventricle, cannulas must be placed in the heart to divert blood to the pump, and all currently approved devices use essentially the same cannulation strategies within the heart and great vessels. For LV support, blood is drained from the LA or, more commonly, the LV apex and returned to the ascending aorta. For RV support, blood is drained from the RA or RV and returned to the main pulmonary artery. These cannulation strategies are common to all VADs currently approved for clinical use and are diagrammed in Figure 21-1.

Figure 21-1 The Thoratec ventricular assist device (VAD) and three cannulation approaches for univentricular left-sided heart support (A) and biventricular support (B and C). This figure illustrates the currently used cannulation strategies for all currently available ventricular assist devices. As described in the text, cannulas are placed in the heart and great vessels to divert blood returning to the failing side of the heart to the pump. The blood collected in the VAD blood chamber is then ejected into the arterial circulation immediately downstream of the failing ventricle. Ao = aorta; LA = left atrial appendage; PA = pulmonary artery; RA = right atrium; Apex = left ventricular apex; IAG = cannula inserted via the interatrial groove and directed toward the LA roof.

(Reprinted with permission from Thoratec Corporation.)

Temporary Ventricular Assist Device Use: Bridge to Recovery

In patients in whom there has been an acute myocardial insult resulting in refractory cardiogenic shock but myocardial recovery is expected, a short-term VAD (e.g., the Abiomed BVS5000; Abiomed, Danvers, MA), an intermediate-term VAD (e.g., the Thoratec VAD system; Thoratec Laboratories, Pleasanton, CA, or the AB5000 ventricle; Abiomed, Danvers, MA), or standard centrifugal devices can support the circulation as a “bridge to recovery.” The Abiomed BVS5000, the Thoratec, and the AB5000 ventricle are paracorporeal, pneumatically driven devices capable of providing pulsatile support for the LV (LVAD), the RV (RVAD), or both ventricles (BiVAD) as needed. With all these devices, the paracorporeal pump heads are connected to inflow and outflow cannulas anastomosed to the heart and great vessels. Table 21-1 summarizes the basic characteristics of these devices. The artificial blood contacting surfaces, unidirectional valves, and pulsatile nature of the pumping mechanism in these devices require that the patient be anticoagulated during support.

Regardless of the device used as a bridge-to-recovery, the patient may potentially be weaned from mechanical support as the ventricle recovers from the acute stunning it has sustained. Unfortunately, complications are frequent and recovery is not assured. In general, the best outcomes are obtained when rescue mechanical circulatory assistance is initiated as soon as the severity of the myocardial insult is recognized and truly appreciated. The best outcomes occur when:

Poor outcomes occur when:

Intermediate- to Long-Term Ventricular Assist Device Use: Bridge to Transplantation

In cases when no myocardial recovery is expected (e.g., end-stage cardiomyopathy) or when an acutely stunned LV fails to recover despite support with a short-term VAD, a long-term “implantable” LVAD (e.g., the Novacor LVAS; World Heart, Ottawa, Canada) is commonly used as a “bridge to transplantation.” By providing effective CO in place of the failed native heart, this technology can stave off the end organ damage resulting from a rapidly deteriorating CO and allows severely decompensated transplant-eligible patients to potentially survive long enough to receive a donor heart. An additional benefit of this application of VADs is an improved quality of life, often as an outpatient, while awaiting a new heart.

The Novacor (Fig. 21-2) and the HeartMate (World Heart, Inc., Oakland, CA) (Fig. 21-3) are the most commonly used bridge-to-transplantation devices for patients with advanced LV failure. Patients with biventricular failure are typically bridged with the Thoratec devices. While there are new and promising devices currently in clinical trials, the Thoratec is presently the only widely available mechanical circulatory support device capable of providing intermediate to long-term support of the native heart as a bridge-to-transplantation for patients who require biventricular support. According to the most recent voluntary Novacor, HeartMate, and Thoratec registries, more than 1700 patients have been implanted with the Novacor, more than 5600 with the HeartMate, and more than 2500 with the Thoratec worldwide. Of those implanted with the Thoratec for bridge to transplantation, 59% required biventricular assistance. Rates of successful bridging to transplantation with these devices are reportedly on the order of 51% to 78%.¹³

Figure 21-2 A, The Novacor LVAS. Inflow and outflow cannulas are at the top, and the drive line, which provides electrical power and system control, can be seen at the bottom right. B, The appearance of an implanted Novacor LVAS. Blood is drained from the LV apex to the pump and ejected into the ascending aorta. The pump head is completely implanted in the preperitoneal space of the abdomen. The current model requires that a cable from the device be tunneled through the abdominal wall to connect to the external system controller and power supply.

(Reproduced with permission from WorldHeart, Inc.)

Figure 21-3 A, The HeartMate LVAS. The inflow and outflow cannulaes are at the top, and the drive line to bring power and system control is at the bottom. B, The appearance of an implanted HeartMate XVE LVAD. Blood is drained from the left ventricular apex to the pump and ejected into the ascending aorta. The pump head is completely implanted in the preperitoneal space of the abdomen. The current model requires that a cable from the device be tunneled through the abdominal wall to connect to the external system controller and power supply.

(Reproduced with permission from Thoratec Laboratories, Inc.)

An implanted Novacor is shown in Figure 21-2, and a HeartMate is seen in Figure 21-3. As depicted, the pump heads of these devices are implanted in a surgically created pocket in the preperitoneal space. Inflow and outflow conduits are connected to the heart and great vessels as shown. Blood is drained to the implanted pump head from the LV apex and is ejected in a pulsatile fashion into the ascending aorta. Adequate intravascular volume status is a critical factor in optimizing pump outputs.

Current versions of these devices require a percutaneous cable to connect the implanted pump heads to an external source of power and system control, potentially increasing the incidence of infection. Additional common complications of long-term VAD use include a high incidence of perioperative bleeding and subsequent potential for cerebral thromboembolism.

The Novacor requires formal anticoagulation with warfarin (target INR 2.5 to 3 times normal) because its blood chamber is composed of smooth polyurethane. In contrast, the blood chamber of the HeartMate has an antithrombogenic lining composed of sintered titanium microspheres that encourages the ingrowth and development of a neointima. For this reason, patients supported by a HeartMate do not require formal anticoagulation and are generally maintained only on aspirin (perhaps in combination with dipyridamole) depending on the preferences of the implanting center.

Permanent Ventricular Assist Device Use: Destination Therapy

A relatively new indication for long-term VAD use is “destination therapy.” Destination therapy refers to the intentionally permanent implantation of an LVAD in a nontransplant eligible patient as a permanent management solution for end-stage cardiac failure. The availability of this indication is a great advance in the treatment of HF because while cardiac transplantation remains the ultimate intervention for advanced HF, the number of donor organs is severely limited in comparison with the number of those who would benefit, and the vast majority of patients with end-stage cardiac disease cannot realistically expect to be transplanted. Effectively, the intentionally permanent implantation of a mechanical assist device may be the best option available if the vast numbers of patients in the population with advanced HF are to survive.

Based on the encouraging results of the REMATCH trial,¹⁴ the HeartMate LVAS was FDA-approved in 2002 for use as “destination therapy” in the United States. Briefly, REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) was conducted to determine if the HeartMate could be effective as an alternative therapy for patients with end-stage cardiac failure who are not eligible to receive a transplant. In addition to patient survival, the study collected data on the implanted patient’s quality of life, the cost of the patient’s care, and any adverse events that occurred during the treatment. In essence, the REMATCH study demonstrated that the use of a left-sided VAD was not only an effective tool to treat patients with advanced HF but also resulted in more than twice the survival rate and an improved quality of life in comparison to optimal medical management. This was especially the case if the patient was younger than 60 years. Summarized results of the REMATCH trial appear in Table 21-2.

Table 21-2 Summarized Results of the REMATCH Trial

Complications of Currently Available Ventricular Assist Devices

Regardless of which short- or long-term device is in use, the major complications of VAD use include coagulopathic bleeding in the perioperative period, potential for thromboembolism during support, and infection. Sepsis is the leading cause of death. Additional complications of VAD use include RV failure while on isolated LV assistance (on the order of 30% due to the induced changes in RV geometry), potential device malfunction, and progressive multisystem organ failure despite VAD support.¹⁵

Cellular Transplantation into the Myocardium

A novel approach to treating severe systolic dysfunction is the injection of harvested autologous skeletal muscle cells into the failing myocardium. This procedure can be performed either surgically at the end of a revascularization procedure or percutaneously in the catheterization laboratory.

The basic understanding of the remodeling process is that viable and contractile cardiomyocytes undergo apoptosis and become replaced by noncontractile tissue. This in turn leads to systolic and diastolic dysfunction. In an attempt to restore functionality, contractile cells are injected into this region. In clinical practice, myoblasts from the patient’s quadriceps muscle have been used. Using the patient’s own tissue has several advantages. First, the complications of pharmacologic immunosuppression are avoided. Second, there are no ethical problems in contrast to those frequently observed when fetal cells are used. Finally, the ease of harvest and processing makes this tissue ideal for this purpose.

Skeletal muscle cells, however, are histologically different from native cardiomyocytes. Adhesion molecules, which are found in native cardiomyocytes, are not found in skeletal myocytes. These adhesion molecules are important for adhesion to the extracellular matrix and for intercellular communication.

A frequently encountered occurrence in the phase I studies was the fact that many patients had episodes of ventricular tachycardia after the procedure. They were successfully treated with amiodarone or electric cardioversion. Phase II studies are now in progress in the United States and Europe. Many other cell types are now being experimentally injected into the myocardium or given intravenously in an attempt to regrow cardiac myocytes. These cells include adult bone marrow stem cells, embryonic stem cells, and cardiac progenitor cells found mainly in the atrium. They have been injected alone or with multiple growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), vasoactive endothelial growth factor (VEGF), and angiopoietin-1, which mobilize progenitor cells and induce new cell growth. The transplanted cells may morph into new cardiac muscle cells or they may improve cardiac function by boosting the growth of new blood vessels or releasing other growth factors that encourage cell proliferation and survival. Any of these effects could explain some of the early positive results seen to date.¹⁶

Gene Transfer in Cardiac Myocytes

Gene therapy has received much interest by the media during the past decade. Multiple research groups are trying to cure or at least alleviate symptoms brought on by HF through gene therapy. To change the genetic programming of a cell it is necessary to inoculate the cell with DNA. To achieve this goal, vectors are being used. Vectors commonly used range from plasmid DNA to different virus types (e.g., adenovirus, herpesvirus). The two cellular pathways that are being targeted are the sarcoplasmic reticulum and the β-adrenergic pathway. The targets of gene therapy are to increase β-adrenergic function, adenylyl cyclase, the V₂ vasopressin receptor, and sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a), while also decreasing phospholambam and β-adrenoreceptor kinase (BARK 1). All of these new therapies hold great promise and many trials are being done.¹⁷

Essential Considerations

Cardiac failure can be the common outcome of a variety of underlying causes, and patients may therefore present with widely varying clinical status. Some may appear quite compromised whereas others may appear surprisingly well compensated despite significant underlying pathophysiology. Regardless of what is planned surgically, achieving hemodynamic stability during the induction and maintenance of anesthesia requires a preoperative knowledge of the status of the coronary arteries (including prior bypass grafts or stents), the extent of any valvular regurgitation and/or stenosis that may be present, and whether there is significant pulmonary hypertension. Additionally, all patients with significant ventricular dysfunction require a thorough preoperative evaluation of the major organ systems (particularly the renal, hepatic, and central nervous systems) for impairment. The anesthetic plan can then take any existing organ dysfunction into consideration.

Preoperative Optimization

Patients with cardiac failure are medically optimized by pharmacologic manipulations of SVR (afterload reduction), β-blockade, and diuresis. Most medications should be continued throughout the perioperative period, but the decision as to whether to withhold angiotensin-converting enzyme inhibitors and diuretics should be made on an individual basis.

Patients with HF often require preinduction optimization of intravascular volume status, pharmacologic manipulations of inotropy and afterload, adjustments to pacemaker settings (where present), and, on occasion, elective placement of an intra-aortic balloon pump.

It is prudent to provide supplemental oxygen and monitor vital signs during the preoperative period. This is especially important if anxiolytic medications are given because this population will not tolerate sudden decreases in sympathetic tone, hypoxemia, or the potentially increased pulmonary vascular resistance that may accompany a respiratory acidosis if hypoventilation results from anxiolysis.

Intraoperative Considerations

Most procedures intended to improve cardiac function will require CPB, but the potential availability of bypass cannot be taken for granted because the function of even a severely depressed ventricle can still get worse, and it is well known that having to emergently institute CPB significantly increases morbidity and mortality. In the prebypass period, further depression of cardiac function and significant increases in ventricular afterload must be avoided, which will increase myocardial oxygen demand and may cause ischemia. Preload, afterload, heart rate, and contractility must be continuously optimized for each patient at all times.

Where CPB will be used, it is generally prudent to consider employing an antifibrinolytic agent in an attempt to decrease bleeding in the postbypass period. In some patients, CPB may not be needed to insert an LVAD.

Anesthetic Agents and Technique

While the usual sedative and hypnotic agents may be tolerated in patients with mild cardiac failure, the failing heart is chronically compensated by a heightened adrenergic state, and removal of that sympathetic tone may lead to rapid decompensation with cardiovascular collapse during anesthetic induction. Patients with severely decreased ventricular function tend to decompensate quickly from physiologic and hemodynamic aberrations (e.g., hypercarbia, hypoxemia, hypotension, bradycardia/tachycardia, sudden alterations in volume status, and loss of sinus rhythm), and agents should be chosen and used in a manner likely to maintain hemodynamic stability. Additionally, agent selection should take into account any coexisting renal or hepatic insufficiency. Intravascular volume status needs to be carefully considered and continuously optimized for each individual patient. Inotropic and vasoactive agents, including ephedrine, phenylephrine, dopamine, epinephrine, milrinone, vasopressin, nitroglycerin, and nitroprusside should be available and judiciously used at the first sign of refractory hemodynamic instability.

Unfortunately, there can be no standard approach to these patients. Despite the perceived similarity of one patient with cardiac failure to another, each individual’s underlying pathophysiology must be carefully considered and then anesthetic agents chosen that will best maintain the hemodynamic goals for that patient.

Traditionally, a technique based on high-dose opioid (e.g., total fentanyl dose 50 to 100 μg/kg, or total sufentanil dose 5 to 10 μg/kg) together with a neuromuscular blocking agent has been used for patients with severely depressed cardiac function. While such a technique will likely result in many hours of hemodynamic stability, potential disadvantages of this technique are that amnesia may not be adequate and the bradycardia and initial chest wall rigidity that typically accompany such an induction must be pharmacologically countered.

Etomidate (0.2 to 0.3 mg/kg IV) is usually the induction agent of choice in these patients because it causes neither a significant reduction in SVR nor a significant decrease in myocardial contractility. The decreases in vascular tone and myocardial contractility that accompany induction with propofol make this drug unsuitable for those with severely depressed cardiac function. Similarly, thiopental, with its propensity to cause myocardial depression and venodilation, with consequent decreases in CO, is not often used for these patients.

As a general rule, high doses of the potent inhalation agents are poorly tolerated in this population. While all of the inhalation agents (including nitrous oxide) are myocardial depressants to varying extents, enflurane and halothane are particularly potent in this regard and are generally avoided in patients with depressed ventricular function. Isoflurane, sevoflurane, and desflurane are more likely to be compatible with hemodynamic stability in the well-optimized patient, although isoflurane and desflurane must be used cautiously due to their particular tendency to decrease SVR. In comparison with the other currently available agents, sevoflurane appears to cause less myocardial depression and decrease in SVR. In addition to direct myocardial depression and vasodilation, the inhaled anesthetic agents may also affect myocardial automaticity, impulse conduction, and refractoriness, potentially resulting in reentry phenomena and arrhythmias.

Although its use in adults has decreased dramatically in recent years, ketamine remains an extremely useful agent in patients with severely decreased ventricular function. A ketamine induction (1 to 2.5 mg/kg IV or 2.5 to 5 mg/kg IM) followed by a maintenance infusion (50 to 100 μg/kg/min) will usually provide excellent hemodynamic stability while ensuring adequate analgesia and amnesia. Where feasible, midazolam is generally provided before giving ketamine in an attempt to lessen the potential post-emergence psychiatric side effects that may occur in some patients. Additional small doses (1 to 2 mg every 2 to 3 hours) or an infusion of midazolam (0.5 μg/kg/min) are often provided when a ketamine infusion is in use. For adults and older pediatric patients, a small intravenous dose of glycopyrrolate (e.g., 0.2 mg) is generally provided to act as an antisialagogue. Once on CPB, the ketamine infusion can be stopped, and moderate-to-high doses of narcotics administered.

Central venous access and pulmonary artery catheterization (PAC) are extremely useful (if not mandatory) in this patient population for several reasons. First, pharmacologic interventions are frequently necessary, and potent inotropic and vasoactive agents are preferably administered to the circulation through a central route. Second, the ability to follow and optimize trends of CO and other hemodynamic indices, as well as the ability to assess the efficacy of pharmacologic interventions to manipulate pulmonary vascular resistance, cannot be overlooked. Third, an extraordinarily useful monitor for evaluating the adequacy of oxygen delivery is measurement of mixed venous oxygen saturation.

Nowhere is TEE a more invaluable intraoperative tool than during surgical procedures intended to improve cardiac function, because the success of many of these procedures depends on specific information provided by the echocardiographer. For example, TEE visualization of the precise mechanism and location of mitral regurgitation often determines the feasibility of valve repair. TEE is used to assess the anatomy of the valve overall, as well as to specifically evaluate the leaflets for abnormal thickening, calcification, mobility, and points of coaptation with respect to the annular plane. Doppler analyses and color-flow mapping complement the two-dimensional evaluation and may provide additional information.

Transesophageal Echocardiography and Ventricular Assist Devices

The role of TEE where mechanical ventricular assist devices are concerned begins before placement of the device, with a TEE evaluation focused on detecting or ruling out specific anatomic pathologic processes that may prevent the device from functioning as intended, or lead to preventable complications, and often must be surgically addressed before starting support by the device.¹⁸

Pre-LVAD placement, TEE is used to detect specific anatomic pathologies that will¹⁹:

During LVAD placement, TEE is used to:

Post-LVAD placement, TEE is used to:

Postoperative Considerations

By and large, improvements in ventricular function will not be immediately apparent in this population after the majority of surgical procedures described in this chapter. In fact, ventricular function is often worse after a major cardiotomy because there has often been some degree of myocardial stunning during CPB despite the best of myocardial protective techniques with modern cardioplegia. Generally, it will be necessary to optimize intravascular volume status and employ pharmacologic manipulations of afterload and contractility. Temporary pacing with epicardial wires placed during surgery is often used to optimize heart rate. In addition, meticulous management of electrolytes, coagulation status, and red blood cell mass is necessary.

One area that is often neglected in this population with sometimes tenuous hemodynamics is postoperative pain management. Patients with severely decreased ventricular function will not tolerate the stress response and tachycardia that accompany postoperative pain due to the increased myocardial oxygen demand (potentially leading to ischemia) and decreased diastolic filling time (potentially leading to decreased stroke volume). This combination is especially deleterious in patients with poor ventricular function and will exacerbate hemodynamic instability.