Selection of Patients for Cardiac Transplantation

I. Cardiac Transplantation: What every physician needs to know.

Cardiac transplantation is the treatment of choice for selected patients with end-stage heart failure. It is estimated that there are 5,700,000 adults in the United States being treated for heart failure (HF), and 620,000 new cases are diagnosed each year.

Registries suggest that between 5% and 10% of patients with HF have advanced disease, which is associated with 1-year mortality in excess of 50% and a poor quality of life. Stage D heart failure, as defined by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, designates patients with refractory HF who might be eligible for specialized advanced treatment strategies (e.g., mechanical circulatory support, heart transplant), or end-of-life care (Figure 1).

Despite the increasing prevalence of advanced heart disease and need for heart transplant, there remains a constant shortage of donor hearts. From 1999 to 2009, the annual number of transplants reported worldwide decreased from 3,992 to 3,742; while in the U.S. over the same time period, the numbers remained essentially flat at approximately 2,200 per year.

The typical center performs between 10 and 19 transplants annually, and can anticipate 1-year patient survival of 90% and median survival of greater than 11 years. For patients surviving to 1 year, the median survival is 14 years.

The marked discrepancy between supply and demand underscores the importance of candidate selection, and has led to consensus guidelines for indications and contraindications to heart transplant. Summary recommendations from a landmark Bethesda Conference highlighted the importance of early evaluation by a multidisciplinary team, the need to address reversible factors, frequent re-evaluation, and the dynamic nature of listing.

II. Diagnostic Confirmation: Are you sure your patient has end-stage heart failure?

The primary indication for cardiac transplantation is end-stage heart failure despite optimal medical, surgical, and device-based therapy. For the primary care provider or cardiologist, factors predicting high 1-year mortality that should trigger referral to a specialized center for consideration of transplant include:

• HF symptoms on minimal exertion or at rest

• Circulatory-renal limitations to angiotensin converting-enzyme inhibitors (or angiotensin receptor blockers) or beta-blockers

• High or increasing doses of diuretics

• Chronic kidney disease associated with hyponatremia, anemia, or hyperuricemia

• Right ventricular failure or secondary pulmonary hypertension, cardiac cachexia, and recurrent admissions for acute decompensated heart failure

In a cohort of more than 14,000 patients, median survival time after the first, second, third, and fourth HF hospitalization was 2.4, 1.4, 1.0, and 0.6 years, respectively (Figure 2). High-risk profile on calculated survival scores (e.g., Seattle Heart Failure Model, Heart Failure Survival Score) may also be used to identify patients with poor prognosis who may benefit from transplant.

The ACC/AHA guidelines have set forth absolute, relative, and insufficient indications for cardiac transplantation.

• Absolute indications include: (1) severe hemodynamic compromise due to HF as defined by refractory cardiogenic shock requiring intraaortic balloon pump or mechanical circulatory support, dependence on intravenous positive inotropic support to maintain vital organ perfusion, or peak oxygen consumption (VO₂) less than 10 ml/kg/min with achievement of anaerobic threshold; (2) severe symptoms of ischemia not amenable to surgical or percutaneous revascularization; and (3) recurrent, symptomatic ventricular arrhythmias refractory to medical therapy or catheter ablation.

• Relative indications include: (1) peak VO₂ between 10 and 14 ml/kg/min (or less than 55% predicted) and major limitation in daily activities; (2) recurrent unstable ischemia not amenable to intervention; (3) recurrent, unstable fluid balance/renal function not due to patient nonadherence with medical therapy.

• Insufficient indications include: (1) left ventricular ejection fraction less than 20%; (2) New York Heart Association (NYHA) functional class III or IV symptoms; (3) peak VO₂greater than 15 ml/kg/min (or greater than 55 percent predicted) without other indications.

Patients with severe HF, who are being considered for MCS, may be classified using profiles defined by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). INTERMACS level 1 patients include those presenting with critical cardiogenic shock, while level 2 patients demonstrate progressive decline despite inotropic support. For these patients, heart transplant evaluation should be completed expeditiously with the understanding that MCS as a bridge to transplant or decision may be needed.

Patients who present acutely (e.g., postcardiotomy shock, acute myocardial infarction) without adequate time for assessment of neurologic or end-organ function should be considered for placement of a percutaneous ventricular assist device.

Temporary support devices can allow for recovery of organ function while providing time to investigate other medical or psychosocial barriers to transplant. Patients with a reversible process such as fulminant myocarditis may bridge to recovery and device explantation over a period of days to weeks.

Patients with moderate-severe heart failure, who do not require MCS or inotropic support, require careful assessment of functional limitation and quality of life. Cardiopulmonary exercise testing provides an objective assessment of exercise tolerance as well as prognosis.

In addition to peak VO₂,VO_{2 measured at anaerobic threshold, the slope of ventilation (VE) to carbon dioxide production (VCO2), and percent predicted VO2 are independent predictors of survival. For patients unable to perform maximal exercise testing, submaximal testing such as the distance walked in 6 minutes can provide important risk stratification.}

A. History Part I: Pattern Recognition:

Evaluation Part I: Indications for heart transplant

In the late 1980s, ischemic cardiomyopathy accounted for more than 50% of all transplants performed worldwide. In the last 5 years, nonischemic cardiomyopathy has become the leading cause of heart disease in transplant recipients.

According to the Registry of the International Society for Heart and Lung Transplantation (ISHLT), the cause of heart disease preceding heart transplant includes: nonischemic cardiomyopathy (53.3%), ischemic cardiomyopathy (37.7%), adult congenital heart disease (CHD) (2.9%), valvular heart disease (2.7%), repeat transplant (2.6%), and miscellaneous (0.8%) (Figure 3).

Other trends in recipient demographics include transplantation of older patients, heavier patients, patients with more comorbidities (diabetes, hypertension), and patients with increased human leukocyte antibody (HLA) sensitization. In addition, compared with a decade ago, the proportion of patients bridged to transplant with mechanical circulatory support has increased from 19% to 32%.

B. History Part 2: Prevalence:

Evaluation Part 2: Relative and absolute contraindications to heart transplant

Guidelines for selecting patients for cardiac transplantation include absolute and relative contraindications, and may vary from center to center. The following factors require evaluation and discussion by a multidisciplinary team:

1. Age: Although older age has long been considered a relative contraindication to transplant, the understanding of the impact of age on outcomes has evolved over time. In the early era of transplant (e.g., 1970s), patients considered eligible for transplant were generally less than 50 to 55 years old.

In the 1980s as posttransplant outcomes improved, most centers considered patients less than 60 to 65 years old to be acceptable candidates. Currently, most heart transplant programs either have no absolute age cut-off or limit candidates to those less than or equal to 70 years old.

In the most recent ISHLT survey, the median age at transplant was 54 years, with more than 25% of patients age 60 or above. In a recent analysis of 14,401 patients transplanted in the U.S. between 1999-2006, those 60 years or older had more comorbidities and lower overall survival compared with their younger counterparts.

However, cumulative 5-year survival was only slightly lower (69% vs. 75%). Other single center studies have reported good outcomes including less rejection in patients 70 years or older, but with increased rates of malignancy and renal failure.

2. Pulmonary hypertension: Pulmonary hypertension is common in patients with advanced heart disease and increases the risk of posttransplant right heart failure and death. Early studies at Stanford University identified four groups of patients ranging from high to low risk based on their resting pulmonary artery pressure/pulmonary vascular resistance (PVR), and response to an acute vasodilator challenge with nitroprusside.

These included: fixed pulmonary hypertension, reactive pulmonary hypertension with systemic hypotension, reactive pulmonary hypertension without systemic hypotension, and normal pulmonary artery pressure/PVR. Commonly used indicators of significant pulmonary hypertension include pulmonary artery systolic pressure >60 mmHg, transpulmonary gradient >15, and PVR >6 Wood units.

Acute pulmonary vasoreactivity testing can be performed with IV nitroprusside or prostacyclin, bolus IV milrinone, or inhaled nitric oxide. More typically, patients are managed over days-weeks with IV vasoactive therapy (milrinone, dobutamine) and diuretics; sometimes with the addition of a phosphodiesterase type 5 inhibitor (e.g., sildenafil). If these agents are not successful at lowering PVR, mechanical circulatory support can be used as a bridge to candidacy.

3. Diabetes mellitus: Approximately 10% of patients undergoing heart transplant are diabetic, and diabetes per se is not a contraindication to transplant. Analyses from UNOS have demonstrated similar long-term survival in patients with uncomplicated diabetes compared to those without diabetes.

However, diabetes associated with moderate-to-severe end-organ dysfunction is considered a relative contraindication to transplant. Patients with diabetic nephropathy should be considered for combined heart and kidney transplant as equivalent outcomes can be expected.

Significant neuropathy with or without peripheral arterial disease increases the risk of nonhealing ulcers and recurrent, potentially life-threatening infection. Prior to transplant, patients should work with their primary care provider or endocrinologist to achieve a target hemoglobin A1c of less than 7.5%.

4. Obesity: Like older age, overweight and obesity are relative contraindications at most transplant centers. Obesity is an independent risk factor for heart failure, and contributes to ventricular remodeling and disease progression.

However, in some HF studies (DIG trial, prospective registries) obese subjects are at lower risk for death compared with their healthy weight controls (so-called “obesity paradox” in heart failure). Between 1987 and 2007, the prevalence of obesity in patients listed for transplant increased from 14% to 29% (Figure 4), and obese patients have longer waiting times and are less likely to receive a transplant.

ISHLT data shows that while body mass index (BMI) has no impact on early mortality posttransplant, patients with a BMI of 35 or more have a 6% lower cumulative survival at 5 years (67% vs. 73%). On average, patients will gain 10.3 kg in the first year posttransplant and this may be exacerbated by chronic steroid use.

Obese transplant patients have decreased functional capacity and quality of life, and are at greater risk of infection and developing cardiac allograft vasculopathy.

5. Malignancy: Active or recent malignancy is generally considered an absolute contraindication to heart transplant. This includes solid tumors, lymphomas, and leukemia.

Patients are required to be disease-free for at least 5 years with an absence of significant cancer-treatment related side effects (e.g., bleomycin or radiation-induced lung disease). Patients with lower grade malignancies such as prostate cancer may be bridged to treatment with mechanical circulatory support.

Skin cancer (except for melanoma) is not a contraindication to transplant, but patients are at high risk of recurrent basal and squamous cell cancer posttransplant. Patients with a history of malignancy should undergo pretransplant consultation with an oncologist, and followed closely posttransplant for recurrent or new cancers. Rarely, nonmetastatic cardiac tumors are an indication for heart transplant.

6. Infection: Active infection with a treatable organism is a relative contraindication to heart transplant. Chronic active hepatitis B or C infection is also considered a contraindication unless viremia is cleared with treatment and liver biopsy does not show cirrhosis or malignancy.

While there have been case reports of good short-term outcomes in patients with HIV, most programs consider HIV/AIDS an absolute contraindication to transplant. This is due to concerns about opportunistic infection with immunosuppression and the perceived decrease in long-term survival due to the underlying disease itself and/or morbidity associated with antiretroviral therapy.

Ventricular assist device infection is not a contraindication to transplant as the treatment is suppressive antibiotics and device removal. Chagas reactivation can occur posttransplant and prophylactic treatment with antitrypanosomal therapy is recommended.

7. Systemic illness: Systemic illness with multiorgan involvement or associated with life-expectancy of less than 2 years is an absolute contraindication to heart transplant. Examples include advanced sarcoidosis, systemic lupus erythematosus, and scleroderma. Generally accepted definitions of severe or irreversible organ dysfunction (alone or in combination) include:

• Renal dysfunction: stage 4 or 5 chronic kidney disease, significant proteinuria; creatinine clearance between 20 to 30 ml/min is a relative contraindication.

• Hepatic dysfunction: biopsy-proven cirrhosis. Total bilirubin more than 2.5 to 3.0 mg/dL is a relative contraindication.

• Pulmonary dysfunction: FEV₁ <1.0 L. FVC, TLC, or DLCO <40% to 50% predicted are relative contraindications.

• Progressive and irreversible neurologic or neuromuscular disorder

The approach to amyloidosis (typically AL type) varies among institutions. Early data showed increased risk of amyloid recurrence and decreased survival posttransplant leading most centers to exclude transplant in this population. However, for patients with primary cardiac involvement, acceptable short and medium-term outcomes have been reported with sequential cardiac and stem cell transplantation, with or without adjuvant chemotherapy.

In this setting, it is important to rule out other organ involvement (i.e., serum creatinine <2.0 mg/dl, alkaline phosphatase < 250 U/L, no pleural effusions, no orthostatic hypotension). Patients with familial amyloidosis may be candidates for combined heart and liver transplant.

8. Other acute and chronic illness: Active peptic ulcer disease, gastrointestinal bleeding, and recent stroke or seizure are all examples of relative acute contraindications to transplant. Acute pulmonary embolism should be treated with systemic anticoagulation for at least 2 to 3 months to allow for lung healing and reduce the risk of postoperative infection.

Cardiac cachexia (BMI <18) should be addressed with oral caloric supplementation or cycled tube feedings under the direction of a metabolic support service, while following serial biomarkers of inflammation and nutrition. Clinically severe peripheral arterial disease or cerebrovascular disease that is not amenable to revascularization is a strong contraindication to transplant, as is an uncorrected abdominal aortic aneurysm >5 cm. Osteoporosis associated with atraumatic fractures precludes transplant in some older woman and rarely men.

9. Special populations: Heart transplant patients may develop severe allograft dysfunction leading to advanced heart failure, and require evaluation for retransplantation. In the U.S., 4.4% of patients listed in the UNOS database undergo retransplantation, while the worldwide prevalence is slightly lower at 2.6%.

The primary target population is patients with chronic allograft dysfunction due to rejection or cardiac allograft vasculopathy, although they are at increased risk for infection and malignancy. In general, patients with primary allograft failure and refractory rejection in the first 6 months are poor candidates for retransplantation.

Adult patients with congenital heart disease (CHD) with failed surgical palliation or not amenable to surgical palliation require special consideration for transplant. Focus on pulmonary hypertension and other end-organ dysfunction (e.g., hepatic and renal dysfunction, protein-losing enteropathy) deserves special evaluation by a multidisciplinary team, including specialists in the care of adults with CHD, cardiac surgery, and cardiovascular imaging.

C. History Part 3: Competing diagnoses that can mimic end-stage heart failure.

Evaluation Part 3: Potentially reversible causes of heart failure

For all patients referred for consideration of heart transplant, an important part of the initial evaluation is to identify and manage potentially reversible factors. Many patients with advanced ischemic cardiomyopathy, for example, will benefit from percutaneous or surgical revascularization.

Older studies suggested that patients with ischemic cardiomyopathy and viable myocardium were more likely to have improvement in left ventricular function with coronary artery bypass grafting (CABG) compared to medical therapy. The Surgical Treatment for Ischemic Heart Failure (STICH) trial randomly assigned 1,212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG to medical therapy alone or medical therapy plus CABG.

The primary outcome of death from any cause occurred in 41% in the medical group and 36% in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval, 0.72 to 1.04; P = .12). Patients assigned to CABG had lower rates of cardiovascular death or hospitalization.

Similarly, patients with advanced heart failure secondary to stenotic or regurgitant valvular disease may avoid or delay the need for heart transplant by undergoing high-risk valvular repair or replacement. Other potentially reversible causes of severe heart failure include tachyarrhythmias (e.g., AF with rapid ventricular response or ventricular tachycardia managed with antiarrhythmics or catheter ablation), heavy alcohol use, fulminant myocarditis, or peripartum cardiomyopathy.

D. Physical Examination Findings.

Evaluation Part 4: Psychosocial support and substance abuse

One of the most important parts of the pretransplant evaluation is comprehensive assessment of a candidate’s psychological status, emotional stability, social support system, and ability to adhere to a complex and lifelong regimen of medications and follow-up care. In addition, all patients are screened for current or prior use of alcohol and tobacco, prescription pain medications, and illicit drugs.

All patients are required to be evaluated by a social worker and psychiatrist, with additional meetings arranged to assess the support of significant others, family members and/or close friends. These evaluations focus on the following:

• Adherence with medical care: Has the patient demonstrated the ability and willingness to follow-up with medical providers for both routine and urgent care? Does the patient seek medical care in a timely fashion when problems arise and follow through with diagnostic or therapeutic recommendations? Has the patient demonstrated adherence to medical and device-based therapy?

• Psychological and emotional stability: Does the patient have any personality traits or disorders, or psychiatric illnesses that could impact on the ability to manage his/her care posttransplant? If the patient has a psychiatric illness, is it controlled with medications? Has he/she recently been hospitalized? Does the patient follow up regularly with a therapist or psychiatrist?

• Adequate caregiver support: To maximize outcomes posttransplant, patients need to be able to rely on at least 1 dedicated caregiver to assist with medications, appointments, etc., especially during the first few weeks or months posttransplant.

• Alcohol use: Does the patient have a history of moderate or heavy alcohol use or alcohol dependence? Has the patient had any alcohol-related complications such as hepatitis, pancreatitis, gastrointestinal bleeding, blackouts, or seizures? Has the patient ever lost his/her driver’s license for driving under the influence (DUI)? In general, most heart transplant programs require at least 6 months of sobriety and plans for ongoing counseling for patients with a history of alcohol dependence prior to listing.

• Tobacco use: Does the patient currently smoke cigarettes or chew tobacco? In general, most heart transplant programs require at least 6 months of complete smoking cessation with documentation of random negative urine cotinine screens prior to listing.

• Illicit drug use: Does the patient currently use or have a history of using illicit drugs, such as marijuana, cocaine, or heroin? In general, most heart transplant programs require at least 6 months of complete freedom from illicit drug use with documentation of random negative urine and/or serum toxicology screens prior to listing.

• Cognitive abilities: Does the patient have any cognitive deficits, including dementia that could limit his or her ability to comply with a complex medical regimen? Formal neuropsychological testing may be helpful to document these deficits and make appropriate accommodations for posttransplant care.

E. What diagnostic tests should be performed?

N/A

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The following is a list of laboratory tests that are part of a routine heart transplant evaluation:

• Chemistry: comprehensive metabolic panel, magnesium, uric acid, phosphorus, LDH, fasting lipid panel, TSH, iron studies, prealbumin, CRP, troponin, BNP, toxicology screen

• Hematology: CBC with differential, ESR, reticulocyte count, hemoglobin A1c, INR, PTT

• Infectious disease: HBV and HCV serologies, CMV, EBV, VZV and toxoplasma serologies, measles screen, HIV

• Urine: urinalysis and culture, toxicology screen, 24-hour collection for creatinine and protein

• Transplant: panel reactive antibody (PRA) screen, tissue typing

• Other: PSA (males over age 50 or with family history)

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The following is a list of imaging and other diagnostic studies that are part of a routine heart transplant evaluation:

• Cardiac testing: electrocardiogram, echocardiogram, cardiopulmonary exercise test, right heart catheterization, left heart catheterization with coronary angiography (if not done within 1 year)

• Vascular studies: carotid ultrasound, lower extremity segmental pressure measurements, and pulse volume recording

• Noncardiovascular testing: chest x-ray, abdominal ultrasound (or CT), pulmonary function tests (spirometry, lung volumes, DLCO)

• Other: Pap smear and mammogram (females based on guidelines), bone densitometry (if indicated), colonoscopy (age >50 or as recommended based on prior testing or family history)

Additional consults:

• Psychiatry

• Social work

• Dental

• Nutrition

• Financial

• Pharmacy

• CT surgery

• Palliative care (if indicated or requested)

III. Management.

Management of sensitized patients waiting cardiac transplantation:

The presence of antibodies to human leukocyte antigens, referred to as humoral or anti-HLA sensitization, is rarely an exclusion for receiving a heart transplant, but increased sensitization can pose significant challenges to both pretransplant and posttransplant care. Most centers currently assess sensitization by checking a panel reactive antibody (PRA) screen, using a panel of color-coded beads that are coated with HLA antigens purified from different donor cells.

A conservative definition of sensitization (expressed as a percentage of a randomly selected population of blood donors to whom the patient has developed anti-HLA antibodies) is a PRA >10%. Different thresholds (e.g., PRA >25%) may be used to decide on the need for prospective crossmatching.

Patients at increased risk of sensitization include multiparous woman, those who have received prior blood transfusions and retransplant candidates. In addition, the presence of mechanical circulatory support appears to increase sensitization due to an immunologic reaction at the blood-VAD interface in addition to blood transfusion at the time of surgery (17% vs. 8% in non-VAD patients in 1 series).

In national and international registries, PRA is an independent predictor of allograft rejection and decreased long-term survival.

Several different treatment strategies have been proposed to decrease pretransplant sensitization, including plasmapheresis plus IV immunoglobulin and/or rituximab. For resistant cases, splenectomy and total lymphoid irradiation have also been tried with limited success.

Augmented immunosuppression at the time of transplant (e.g., induction with antithymocyte globulin) can also be used to reduce the likelihood of antibody-mediated rejection posttransplant. No consensus guidelines exist on the evaluation and management of anti-HLA sensitization.

IV. Management with Co-Morbidities

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission

B. What's the Evidence for Specific Management and Treatment Recommendations?

Mancini, D, Lietz, K. “Selection of cardiac transplantation candidates in 2010”. Circulation. vol. 122. 2010. pp. 173-183. (This is a clear review of important developments pertaining to the optimal timing of heart transplant and the use of mechanical circulatory support as a bridge to transplant. In addition, contemporary challenges in candidate selection are discussed.)

Hunt, SA, Haddad, F. “The changing face of heart transplantation”. J Am Coll Cardiol. vol. 52. 2008. pp. 587-598. (More than 40 years have passed since the first human heart transplant. In this review, the authors provide a senior clinician’s perspective on the changing face of heart transplantation, including an evolving patient population and advances in transplant immunology, organ preservation, and cardiac allograft vasculopathy.)

Stehlik, J, Edwards, LB, Kucheryavaya, AY. “The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report—2011”. J Heart Lung Transplant. vol. 30. 2011. pp. 1078-1094. (The International Society for Heart and Lung Transplantation Registry summarizes data on heart transplant patients from nearly 400 heart centers worldwide. This annual report includes important statistics on donor, recipient, and center demographics, provides an overview of immunosuppressive therapies, and examines survival and mortality risk factors posttransplant.)

Goldstein, DJ, Bello, R, Shin, JJ. “Outcomes of cardiac transplantation in septuagenarians”. J Heart Lung Transplant. vol. 31. 2012. pp. 679-685. (Using de-identified data provided by the United Network for Organ Sharing, Goldstein et al demonstrate that selected patients age 70 years and older with advanced heart failure can derive substantial benefit from heart transplantation with less rejection. However, compared with patients aged 60 to 69 years, long-term survival is modestly impaired.)

Kittleson, MM, Kobashigawa, JA. “Management of advanced heart failure: the role of heart transplantation”. Circulation. vol. 123. 2011. pp. 1569-1574. (In this Clinician Update, the authors present the case of a 65-year-old man with idiopathic dilated cardiomyopathy, who is referred for heart transplant evaluation. They propose a useful algorithm for managing advanced heart disease patients that includes assessment of functional and hemodynamic status, while addressing reversible factors and ensuring that there are no medical or psychosocial contraindications to transplant.)

Wilson, SR, Mudge, GH, Stewart, GC, Givertz, MM. “Evaluation for a ventricular assist device: selecting the appropriate candidate”. Circulation. vol. 119. 2009. pp. 2225-2232. (This review focuses on the management of patients who are listed for heart transplant and develop progressive clinical and hemodynamic deterioration requiring consideration of ventricular assist device (VAD) as a bridge to transplant. The authors discuss the unique clinical dilemmas encountered in selecting candidates for therapy with currently available VADs, with particular attention to right ventricular and end-organ function.)

Haddad, H, Isaac, D, Legare, JF. “Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary”. Can J Cardiol. vol. 25. 2009. pp. 197-205. (The Canadian Cardiovascular Society published its consensus conference on cardiac transplantation in 2003. This update provides new evidence in the understanding of clinical issues and management of heart transplantation, and reviews the indications and contraindications for transplant.)

Stewart, GC, Givertz, MM. “Mechanical circulatory support for advanced heart failure: patients and technology in evolution”. Circulation. vol. 125. 2012. pp. 1304-1315. (This lead article in a new series on Advances in Mechanical Circulatory Support focuses on surgically implanted left ventricular assist devices used in adults with advanced heart failure, and highlights the evolution in both patients and technology.)

Teuteberg, JJ, Mathier, MA, Shullo, MA, Antman, E, Sabatine, MS. “Cardiac transplantation and circulatory support devices”. Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease. 2012. (This is a comprehensive textbook chapter on the role of “advanced therapies”—cardiac transplantation and mechanical circulatory support—in the management of patients with advanced heart disease. Important candidacy issues, including age, comorbidities, and immunologic sensitization, are discussed.)

Hunt, SA, Abraham, WT, Chin, MH. “2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation”. Circulation. vol. 119. 2009. pp. e391-e479. (In 2005, the American College of Cardiology Foundation and American Heart Association published comprehensive practice guidelines for the diagnosis and management of heart failure in adults. This 2009 update reflects a consensus of expert opinion after a thorough review of late-breaking clinical trials and other new data deemed to have an impact on patient care. A new section on the management of the hospitalized patient is included.)

Lindenfeld, J, Albert, NM, Boehmer, JP. “HFSA 2010 Comprehensive Heart Failure Practice Guideline”. J Card Fail. vol. 16. 2010. pp. e1-194. (The first guideline developed by the Heart Failure Society of America focused narrowly on the pharmacologic treatment of patients with chronic heart failure. In this 2010 update, the practice guidelines committee expands the discussion of acute decompensated heart failure and adds sections on genetic evaluation of cardiomyopathy and end-of-life care.)

Mehra, MR, Kobashigawa, J, Starling, R. “Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006”. J Heart Lung Transplant. vol. 25. 2006. pp. 1024-1042. (This consensus document by the International Society for Heart and Lung Transplantation provides guidelines on the listing criteria for cardiac transplant. Areas of focus include cardiopulmonary exercise testing, use of heart failure survival scores, and role of right heart catheterization. A detailed discussion of comorbidities, including diabetes and renal dysfunction, and psychosocial barriers to transplant is included.)

C. DRG Codes and Expected Length of Stay.

Transplant; heart (V42.1)

Acute on chronic systolic and diastolic heart failure (428.43)

Shock without mention of trauma; cardiogenic shock (785.51)

Other primary cardiomyopathies (425.4)

Organ or tissue replaced by other means; heart assist device (V42.31)

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