Doi:10.1016/j.healun.2006.06.005

Heart Rhythm Considerations in Heart Transplant Candidates and
Considerations for Ventricular Assist Devices: International
Society for Heart and Lung Transplantation Guidelines for
the Care of Cardiac Transplant Candidates—2006
Edoardo Gronda, MD, Robert C. Bourge, MD, Maria Rosa Costanzo, MD, Mario Deng, MD, Donna Mancini, MD,Luigi Martinelli, MD, and Guillermo Torre-Amione, MD 1. ELECTROPHYSIOLOGIC CONSIDERATIONS IN HEART
RV) may increase the risk for the development of TRANSPLANT CANDIDATES
heart Irrespective of the underlying pathol- 1.1. Cardiac Re-synchronization Therapy With or Without
ogy, QRS Ͼ120 milliseconds is associated with in- Implanted Cardioverter Defibrillator as Part of
Optimal Treatment
1.2. Cardiac Re-synchronization Therapy
Regardless of underlying etiology, heart failure may beassociated with an abnormal sequence of ventricular Recommendations for cardiac re-synchronization ther- contractions, referred to as cardiac or ventricular dys- synchrony. This abnormality may be due to both dis- 1. Potential transplant candidates with cardiac dys- turbed electrical activation and regional abnormalities in contraction due to ischemia, myocardial scarring or (NYHA) Class III or IV symptoms, despite maxi- replacement of myocardium by infiltrative diseases mum medical therapy, should be strongly consid- Approximately 33% of patients with systolic heart fail- ered for cardiac re-synchronization therapy (CRT) ure have evidence of abnormal electrical activation on surface electrocardiogram (ECG), seen as a QRS dura- 2. The use of an implantable cardioverter defibrilla- tion of Ͼ120 milliseconds, most commonly as a left tor (ICD), especially in patients with persistent bundle branch block The ventricular contrac- NYHA Class III or IV symptoms, should be consid- tion pattern associated with LBBB results in the follow- ered because it may further decrease mortality in this population (Level of Evidence: B).
with movement paradoxical to the lateral wall of theleft ventricle, and thus a decrease in regional left CRT involves the use of pacing to specifically im- ventricular ejection fraction a delay in mitral prove or negate the effects of cardiac dyssynchrony, valve opening and aortic valve closure resulting in a usually by pacing the LV lateral wall. However, specific shortened left ventricular (LV) filling and mitral lead placement may depend on the underlying conduc- regurgitation, caused or aggravated by dyssynchronous tion abnormality. Early studies in the 1990s proved that activation of papillary muscles and the surrounding the short-term use of pacing to re-synchronize the heart myocardium and incomplete closure of the mitral valve resulted in correction of abnormal septal motion, an increase in LV filling time, and an improvement in In addition to dyssynchrony resulting from underly- mitral regurgitation. Short-term animal studies showed ing cardiac pathologies, some data suggest that car- improvement in hemodynamics and these results were diac dyssynchrony induced by a pacemaker (right ventricular [RV] or combined right atrial [RA] and The development of LV leads that can be reliably placed into the coronary sinus to pace the LV free wall hasallowed for multiple clinical studies to evaluate the effect From the International Society for Heart and Lung Transplantation, of CRT on hemodynamics, quality of life, NYHA class, exercise capacity and overall clinical These Submitted May 27, 2006; revised May 27, 2006; accepted June 16, early, non-controlled or non-randomized studies largely Reprint requests: Amanda Rowe, Executive Director, ISHLT, 14673 showed improvements in clinical parameters. Three Midway Road, Suite 200, Addison, TX 75001. E-mail: amanda.rowe@ large, randomized studies have since set the stage for the regulatory approval of CRT therapy and its accep- J Heart Lung Transplant 2006;25:1043–56.
tance as part of the mainstay of therapy for advanced Copyright 2006 by the International Society for Heart and Lung heart failure (NYHA Class III or IV, despite maximal Transplantation. 1053-2498/06/$–see front matter. doi:10.1016/j.healun.2006.06.005 The Journal of Heart and Lung Transplantation The first randomized, double-blind trial to evaluate Device placement was successful in 95% of CRT was the Multicenter InSync Randomized Clinical patients in the CRT group. Death or first hospitalization was significantly reduced by 37% in the CRT group by through 2000, the study included 453 patients with the end of the study, with an average follow-up of 29.4 LVEF Ͻ35% and QRS Ͼ130 milliseconds, with NYHA months (HR 0.63; 95% CL 0.51 to 0.77; p Ͻ 0.001). In Class III or IV heart failure despite optimized medical addition, heart failure hospitalizations, heart failure therapy. These patients were randomized in a double- symptoms and patient QOL were significantly improved blind fashion to CRT therapy vs control for 6 months in the CRT group. A 36% reduction in all-cause mortality (all received CRT implantation, with the device turned was seen in the CRT group, with 82 deaths in that on in only the CRT group). The success rate for device group, compared with 120 deaths in the control group implantation was 92% (in early use the LV leads were (HR 0.64; 95% CL 0.48 to 0.85; p Ͻ 0.002).
placed via the coronary sinus). The study was not Interestingly, the incidence of sudden death was powered to show a difference in survival. However, all unchanged in the treated arm (32%) as compared with primary and secondary end-points significantly favored the control arm (35%), suggesting that a defibrillator CRT therapy, including death or worsening heart failure might further decrease the incidence of sudden death.
requiring hospitalization (hazard ratio [HR] 0.60; 95% CRT has been clearly shown to improve morbidity confidence limit [CL] 0.37 to 0.96; p ϭ 0.03) and and mortality in patients with NYHA Class III or IV heart hospitalization for worsening heart failure (HR 0.50; failure, despite maximized medical therapy with evi- 95% CL 0.28 to 0.88; p ϭ 0.02). Other secondary end- dence of ventricular dyssynchrony by surface ECG points that significantly favored CRT (some evaluated in sub-studies) included improvement in quality of life Published studies largely assessed cardiac dyssyn- (QOL) score (QOL –18 vs –9 [lower score better]; p ϭ chrony via evidence of conduction abnormalities on the 0.001), LVEF by echocardiography (4.6% vs – 0.2%; p Ͻ surface ECG. However, approximately 33% of patients 0.001), and an improvement in clinical composite heart who undergo CRT therapy receive no demonstrable failure score (improved 67% vs 39%, worsened 16% vs improvement in morbidity. It is also clear that a wide 27%; p Ͻ Despite 2001 U.S. Food and Drug QRS alone does not assure that ventricular dyssyn- Administration (FDA) approval of the CRT device for chrony is present, and that mechanical ventricular use in the USA, important questions about the use of dyssynchrony can be present in patients with a normal The Comparison of Medical Therapy, Pacing, and techniques (interventricular mechanical delay, septal- Defibrillation in Heart Failure (COMPANION) trial was a to-posterior wall motion delay, tissue Doppler imaging, larger study (N ϭ 1,520 patients), with a similar studypopulation to that of the MIRACLE trial (except the QRS strain and strain rate, tissue tracking),and radionu- duration cut-off was Ն120 milliseconds), comparing optimum medical therapy to CRT, or to CRT with an relatively small studies for the assessment of mechanical cardiac dyssynchrony, and to evaluate the effects of study, conducted from 2000 to 2002, was not blinded CRT. Further work is needed to assess optimal CRT to patients or investigators. At 12 months of follow up, both CRT therapy and CRT with ICD decreased the risk It is important to note that severely ill patients, of death or hospitalization for any cause (CRT: HR 0.81; including those who need inotropic or device support, 95% CL 0.69 to 0.96; p ϭ 0.014; CRT with ICD: HR 0.80; were largely excluded from the earlier clinical trials.
95% CL 0.68 to 0.95; p ϭ 0.010). At 12 months, CRT These patients are today the most frequent heart trans- resulted in a marginally significant reduction in death plant candidates. The risk of implantation of a CRT in an (HR 0.76; 95% CL 0.58 to 1.01; p ϭ 0.06), and CRT with end-stage heart failure patient (Stage D), who is other- ICD resulted in a 36% reduction in risk of death (HR wise is a good candidate for heart transplantation, may 0.64; 95% CL 0.48 to 0.86; p ϭ 0.003). Thus, the effect of CRT on survival in patients was not affirmed, butsuggested.
1.3. Implantable (Primary and Secondary Prevention)
The Cardiac Re-synchronization–Heart Failure (CARE- and Wearable External Defibrillator as a Bridge
HF) study was a randomized (CRT vs control), non- Therapy to Heart Transplantation
blinded study of 813 patients in NYHA Class III or IV Recommendations for use of defibrillators include: with intraventricular dyssynchrony and LVEF Յ35% and a primary end-point of death (any cause) orunplanned hospitalization for a cardiovascular event, 1. An ICD for secondary prevention should be al- with death alone pre-specified as a principal secondary ways considered (Level of Evidence: A).
The Journal of Heart and Lung Transplantation 2. An implanted or wearable ICD should be provided dilated cardiomyopathies compared with standard ther- for Status 1B patients who are discharged home apy or amiodarone. Absolute mortality was decreased given that the wait for transplantation remains only in the ICD arm. There was no improvement in significant (Level of Evidence: C ).
survival during the first year, but at 5 years a 7.2% 3. Amiodarone should be used as the agent of choice when anti-arrhythmic therapy is necessary to pre- The Defibrillators in Non-ischemic Cardiomyopathy vent recurrent atrial or symptomatic ventricular Treatment Evaluation (DEFINITE) compared medi- arrhythmias despite its numerous side effects cal therapy alone with medical therapy plus ICD in patients with non-ischemic cardiomyopathy; NYHA 4. Re-synchronization therapy in advanced heart fail- Class I, II or III heart failure; and LVEF Ͻ36%.
ure patients should be considered together with a The ICD was associated with a reduction in all-cause defibrillator (Level of Evidence: B).
mortality that did not reach statistical significance, but itwas consistent in terms of magnitude of effect (30%) with the findings of MADIT-II and SCD-HeFT.
1. It is reasonable to consider placement of a defi- brillator in patients with Stage D failure who are bined CRT and ICD in patients with heart failure and candidates for transplantation or LVAD destination low LVEF, and demonstrated a survival benefit as a therapy (see subsequent considerations for mechan- secondary end-point. As a result of these trials, use of ical circulatory support device [MCSD] referral: defibrillators for primary prevention of sudden death is bridge or destination) (Level of Evidence: C ).
rapidly expanding in patients with NYHA Class II or IIIheart failure. Accordingly, by the time patients with Patients with heart failure and reduced LVEF are at NYHA Class II or III heart failure progress to Stage D high risk for sudden death. Although ventricular tachy- heart failure and are transplant candidates, an ICD may arrhythmias are the most common rhythms associated already be implanted. This is particularly important as with sudden death, bradycardia and electromechanical studies on primary prevention of sudden death in dissociation are also common in patients with advanced patients with NYHA Class IV/Stage D patients have not been performed. Generally, placement of an ICD for Appropriate heart failure therapy (␤-blockers, aldo- primary or secondary prevention of sudden death in sterone inhibitors) can help reduce the risk of sudden Stage D patients is not recommended as the impact of death, but the absolute frequency of sudden death ICD on survival is generally not seen until 1 year after Patients with heart failure and reduced LVEF are Few studies have reported the incidence of arrhyth- candidates for secondary prevention of sudden death mic events in Status 1B patients. Lang et reported from ventricular tachyarrhythmias if there is a history of on data from 155 UNOS Status 1B patients, of whom 91 previous cardiac arrest, documented sustained ventric- were discharged. Twenty-five had an implanted defibril- ular arrhythmias, or syncope.These patients all lator and 13 wore an external device. Of those patients have a high risk of recurrent events and are candidates with defibrillators, no significant arrhythmic events were recorded. Sudden death episodes occurred in Indications for ICD placement for primary prevention 2 patients, both of whom declined external defibrilla- of sudden death in patients with heart failure and tors. Brozena et described 60 patients who were reduced LVEF have recently been clarified by several discharged to home inotropic therapy. All patients had large trials, most notably the Multicenter Automatic an ICD. The average duration of participation was 160 Defibrillator Implantation Trial II and Sud- days with 7 events that resulted in ICD firing. Six den Cardiac Death in Heart Failure Trial (SCD-HeFT) patients had an appropriate defibrillator shock for treat- In these trials, patients were treated with optimized ment of ventricular tachycardia, and 1 for supraventric- medical therapy and had documented, persistent severe ular arrhythmia. These studies probably underestimate LV dysfunction for Ն6 months. MADIT-II demonstrated the risk for arrhythmic events given the relatively short that ICD, compared with standard medical therapy, duration of follow-up. Alternative strategies for preven- decreased total mortality for patients with LVEF Յ30% tion of sudden death in Stage D patients include use of after remote myocardial infarction (MI). Patients with amiodarone, as this anti-arrhythmic agent may be asso- symptomatic heart failure in this trial achieved the most ciated with neutral or positive effects in patients with heart failure and low In the recent SCD-HeFT The SCD-HeFT examined the benefit of ICD implan- investigation, administration of amiodarone to patients tation for patients with LVEF Ͻ35%, and NYHA Class II with symptomatic heart failure and low LVEF did not or III heart failure symptoms from both ischemic and improve outcomes when compared with placebo ther- The Journal of Heart and Lung Transplantation However, patients with ICD and recurrent ven- tricular arrhythmias may require amiodarone therapy with or without catheter ablation of the arrhythmiafocus.
1. In patients Ͼ60 years of age, a thorough evalua- Use of wearable defibrillators can serve as a bridge to tion for the presence of other clinical risk factors transplant. This is particularly true for patients with should be done (Level of Evidence: C ).
systemic or device infections or in patients whose 2. Age should not by itself be considered a contrain- anticipated waiting time to transplant is short, such as dication to mechanical circulatory support (Level candidates with blood types A and B. Use of the Lifecor system has been reported in 289 patients who were Background. An inverse relationship is generally either awaiting placement of an implantable device reported between ages Ͼ60 to 65 years and outcome, (BIROAD study) or patients with heart failure and although encouraging results have recently been ob- reduced ejection fraction (WEARIT This exter- nal defibrillator system consisted of 2 gel-filled defibril-lator electrodes, 4 sensing ECG electrodes, and a vibra- 2.2. Body Size
tor incorporated into a patient-worn belt. ECG signals are continuously monitored for ventricular tachycardia 1. The use of pulsatile intracorporeal devices (e.g., or fibrillation at rates programmed into the device. A HeartMate XVE, Thoratec Corp., Pleasanton, CA; series of alarms, initially vibratory then an audible tone Novacor LVS, WorldHeart Corp., Oakland, CA) followed by voice alarm, are activated by a detected should be limited to patients with a body surface arrhythmia. If the system is not disabled, the device area (BSA) Ͼ1.5 m2. For smaller individuals, the delivers a shock at a pre-programmed level. In this trial, use of paracorporeal or axial-flow devices should 6 successful defibrillations occurred out of 8 attempts.
be considered (Level of Evidence: C ).
The 2 unsuccessful defibrillations occurred in patientswho did not properly apply the defibrillator electrodes.
Background. The large size of intracorporeal pulsa- One of these events was non-fatal as the patient was tile devices requires adequate thoracic and abdominal successfully cardioverted using another external de- capacity. This limitation is overcome by the availabil- vice. This device has been approved for use by the FDA ity of paracorporeal, small-sized pulsatile devices or and is available for widespread use.
by the use of intracorporeal/intraventricular axial-flow 2. RELEVANT ISSUES IN HEART TRANSPLANT
2.3. Renal Function
CANDIDATES CONSIDERED FOR MCSD THERAPY
In the decisionmaking process before MCSD implan- 1. All patients evaluated for MCSD therapy should tation other cardiac, non-cardiac and technical fac- have their creatinine and blood urea nitrogen tors must be considered. The following consider- (BUN) measured. Patients with a creatinine Ͼ3.0 ations refer to the most relevant issues in patient mg/dl are at higher risk. Patients with serum evaluation and management for MCSD therapy. Due creatinine above this value may be considered to the many available devices and diverse experi- MCSD candidates if renal failure is acute and renal ences, the present statement cannot cover all the recovery is likely (e.g., acute renal failure in young specific issues that might be encountered in patient patients with previously normal renal function) Because the spectrum of uses of ventricular assist device (VAD) support includes not only bridge to transplantation but also weaning and destination ther- 1. Patients dependent on long-term dialysis should apy, the former may be changed to one of the latter two not be considered MCSD candidates (Level of options, balancing possible advantages and disadvan- The recommendation for MCSD therapy is based on a Background. Renal dysfunction is a strong determi- comparison of short- and long-term survival and QOL nant of unsuccessful MCSD support but in many cases it outcomes with conventional therapy. The following recommendations must not be viewed in isolation, but In addition to clinically established parameters, such in the context of their cumulative effect on outcomes in as serum creatinine and BUN,pre-operative cre- atinine clearance has also been shown to correlate The Journal of Heart and Lung Transplantation gaining increasing relevance. This score includes the ogy and Chronic Health Evaluation (APACHE) II score logs of bilirubin (mg/dl), creatinine (mg/dl), interna- has been used in peri-operative renal dysfunction risk tional normalized ratio (INR) and cause of underlying Besides bilirubin, liver enzyme levels alsopredict survival after MCSD implantation as a bridge to 2.4. Pulmonary Function
2.6. Coagulation Disorders
1. All patients evaluated for MCSD therapy should have chest X-ray and pulmonary function tests if feasible. Mechanical ventilation in the absence of 1. All patients evaluated for MCSD therapy should significant pre-existing pulmonary dysfunction or have complete routine coagulation tests per- inflammatory infiltrates is a risk factor but should formed. Patients with a spontaneous INR Ͼ2.5 are not be considered an absolute contraindication to at increased risk of bleeding complications (Level VAD support. A lung computerized tomography (CT) scan should be considered in select patientsto rule out undiagnosed conditions at chest X-ray 1. Patients with heparin-induced thrombocytopenia are generally not considered MCSD candidates(Level of Evidence: C ).
1. Patients with severe pulmonary dysfunction con- traindicating heart transplantation (e.g., forced Background. Most clinical decisions are currently expiratory volume in 1 second [FEV ] Ͻ1) should guided by measurement of the INR. However, as coag- not be considered MCSD candidates (Level of ulation control is crucial, measurements such as acti- vated protein C (APC), thrombomodulin and endothe-lial cell protein C receptor may provide more precise Background. Mechanical ventilation in cardiogenic shock is a severe risk factor for poor post-implantoutcome. Recent pulmonary embolism or inflammatory 2.7. Infectious Diseases and
parenchymal infiltrates can lead to the development of Immunoinflammatory Activation
infective foci, which can be difficult to treat under 1. All patients evaluated for MCSD therapy should 2.5. Hepatic Function
have a thorough screening for infectious foci. Any ongoing infection should be identified and ade-quately treated before MCSD implantation. In 1. All patients evaluated for MCSD therapy should have liver function assessment. Patients with an particular, all conditions that might enhance the alanine aminotransferase (ALT) or aspartate ami- risk of fungal infection should be considered and notransferase (AST) Ͼ3-fold control values are properly managed (Level of Evidence: C ).
at higher risk. Biventricular support may be considered the first option in cases of hepaticdysfunction associated with RV failure (Level of 1. Patients with an acute systemic infection should not be considered MCSD candidates (Level ofEvidence: C ).
Background. Sepsis is one of the most common 1. Patients with cirrhosis and portal hypertension causes of death after MCSD implantation.In should be excluded from MCSD implantation this context, an elevated white cell count (Ͼ10,000/␮l) before MCSD implantation constitutes a risk factor for Background. Elevated serum bilirubin and deficiency in clotting factors have a serious adverse impact on defense system turns its lifesaving potential into auto- post-implant outcomes. However, because hepatic dys- function is often a consequence of right ventricular (RV) failure, it is a strong predictor of the need for Fungal infection deserves special attention as MCSD patients are more prone to fungal infection and less stage liver disease (MELD) score prognostic model is The Journal of Heart and Lung Transplantation 2.8. Arrhythmias
aortic insufficiency is present. The replacement of a mechanical prosthesis with a bioprothesesshould also be considered (Level of Evidence: C ).
1. Biventricular support for recurrent sustained 2. Anti-coagulation therapy is strongly advised when a ventricular tachycardia or ventricular fibrillation prosthetic valve is present (Level of Evidence: C).
should be considered only in the presence of 3. Severe mitral stenosis should be treated and, if untreatable arrhythmogenic pathologic substrate weaning from MCSD is foreseen, significant mitral (e.g., giant cell myocarditis). Otherwise, appropri- insufficiency should also be corrected (Level of ate medical anti-arrhythmic therapy, anti-bradycar- dia pacing, ICD implantation or ventricular tachy-cardia ablation can generally adequately control Background. More than minimal aortic insufficiency can rapidly evolve to moderate/severe grades due to LVAD support (Level of Evidence: C ).
continuously elevated pressure in the aortic root cre-ated by the pump and not counteracted by phasic LV Background. Ventricular tachycardia and ventricular pressure rise. Mitral stenosis can reduce native ventric- fibrillation may resolve after adequate LVAD support ular filling and limit the output of the device. Mitral except in the case of underlying pro-arrhythmic pathol- insufficiency does not interfere with MCSD function but ogy. During LV MCSD support, tachyarrhythmias or bra- can adversely affect future weaning and explantation.
dyarrhythmias are generally tolerated in the presence of Severe tricuspid regurgitation should always be consid- normal pulmonary resistance due to the Fontan-like circu- ered as an adjunctive mechanism of worsening of RV lation, and the need for biventricular support is uncom- In rare situations, the implantation/use o f either anti-bradycardia pacing or anti-tachycardia de- Presently, a consensus does not exist on whether and how severe tricuspid regurgitation should be treated.
2.9. Right Ventricular Function
2.11. Neurologic Function
1. Evaluation of reversibility of pulmonary hyperten- 1. A thorough neurologic examination should be sion and RV performance should be performed performed to determine potential neurologic risk before MCSD implantation. In the case of irrevers- factors and contraindications for MCSD implanta- ible pulmonary hypertension, RV failure or multi- tion. Specifically, post-stroke motor deficits should organ dysfunction, biventricular support should be assessed to determine the ability of the patient to be considered. Patients Ͼ65 years of age with cope with the device. In emergency cases with biventricular failure are at the highest risk for RV uncertain neurologic recovery, a short-term MCSD, failure. Thus, they should be considered with such as a paracorporeal centrifugal pump, should be great caution as MCSD candidates (Level of Evi- adopted, allowing for recovery and full evaluation of long-term MCSD candidacy. A recent or evolving Background. RV failure constitutes one of the most stroke is considered at least a temporary contraindi- powerful predictors of adverse post-MCSD outcomes cation (Level of Evidence: C ).
The functional status of the RV and its relationship to the Background. Knowledge about the neurologic status pulmonary circulation are of utmost importance in the of patients referred for mechanical assistance on an decisionmaking process for MCSD implantation as is emergency basis is crucial to determine the appropri- the differential indication between the use of an LVAD or biventricular assist device Low RV sys-tolic pressure coupled with elevated right atrial (RA) 2.12. Nutritional Status
pressure and low systolic stroke volume indicates se- vere RV impairment with poor reversibility prospects.
1. Cachexia should be considered a strong risk factor 2.10. Valvular Diseases
1. When using a completely unloading pulsatile Background. Cardiac cachexia is a syndrome charac- MCSD, such as the Novacor, HeartMate I or Tho- terized by striking weight loss leading to a BMI Ͻ21 ratec, the aortic valve should be sutured or re- kg/m2 in males and Ͻ19 kg/m2 in females.Heart placed with a bioprostheses when more than mild failure patients may be characterized by the presence of The Journal of Heart and Lung Transplantation anorexia, early satiety, weight loss, weakness, anemia and edema. These features occur to a variable extent in Patients with a positive psychiatric history, or data different patients and may change in severity during the concerning symptoms should be referred to a psychia- course of a patient’s illness. The cachexia syndrome in trist or therapist as early as possible to ensure that advanced heart failure patients with low peak VO is a proper treatment is initiated or optimized.
strong independent indicator of poor (see Methods of coping with stress and illness should be Section 5: “Nurse and Social Worker Management of discussed so that the transplant team will be able to adjust care for each patient’s needs. Standardized test-ing, such as the Minnesota Living with Heart Failure 2.13. Multiorgan Failure
Scale or the Sickness Impact Profile, should be admin- istered if possible, as this may provide more objective 1. Multiorgan failure should be considered a strong information regarding patient coping skills. Patients and contraindication to MCSD (Level of their care providers should be referred to support An assessment should be done to determine if the Background. Multiorgan failure, defined as multiple, patient has history of substance abuse, specifically a progressive, end-organ dysfunction with critical unman- history of tobacco, alcohol or drug If a patient ageable impairment of vital functions linked to the is already involved in a recovery program, the continu- central nervous system, kidney, liver and lung, is almost ation of this form of treatment should be highly encour- invariably associated with poor post-implant outcome aged. If the patient is not presently in recovery or in a drug rehabilitation program, this should be mandated.
2.14. Malignancies
Referral to a substance abuse expert should be made asan adjunct to therapy.
1. Patients with potentially curable tumors may un- 3. RELATION BETWEEN INOTROPE THERAPY AND MCSD:
dergo MCSD implantation as a potential bridge to IMPLANTATION AS BRIDGE TO HEART TRANSPLANTATION
heart transplantation (Level of Evidence: C ).
Background. Although active malignancies are an 1. MCSD therapy should be considered when the absolute contraindication to heart transplantation, in patient requires incremental increases in inotro- selected cases, mechanical support can be utilized to pic or diuretic drug doses or additional parenteral extend life expectancy to allow proper oncologic agents, or deterioration in status occurs that in- treatment before transplantationor as destination cludes signs of end-organ dysfunction despite these alterations (Level of Evidence: C ).
2.15. Psychologic and Psychiatric Conditions
Background. The use of inotropic therapy, specifi- cally the use of dopamine, dobutamine and phosphodi-esterase inhibitors (milrinone and enoximone), should 1. A thorough psychiatric examination should be be reserved for patients with refractory symptoms of performed to determine potential psychiatric risk heart failure and impending organ dysfunction as a factors and contraindications for MCSD implanta- consequence of the heart failure syndrome, typically for tion. Specifically, patients with a significant psy-chiatric history, alcoholism or drug addiction a low-output state. It has become increasingly clear that should be referred to a psychiatrist or therapist as the use of dobutamine and milrinone/enoximone have early as possible to ensure that proper treatment is long-term adverse effects on however, it is initiated or optimized (Level of Evidence: C ).
also clear that these drugs are effective in improvinghemodynamics, leading to reversal of end-organ dys- 1. Active psychiatric disease is a contraindication for It is not clear whether the elective move toward MCSD implantation as many psychiatric conditions MCSD therapy in a stable heart transplant candidate can lead to non-compliance (Level of Evidence: C).
awaiting transplantation on long-term inotropic therapyis indicated.
For further details see Section 5, “Nurse Management and Social Worker Management of MCSD Candidates.” 1. Weaning from inotropes should be attempted should be explored in detail. A history of depression, when stable clinical conditions are achieved, but The Journal of Heart and Lung Transplantation repeated withdrawal should be avoided if depen- support or those showing signs of progressive end- dence is well established (Level of Evidence: C ).
organ damage or multi-organ failure due to heart failure.
There is very little information available, however, Background. Most patients treated with inotropic that helps determine the optimal time for recommen- and/or vasodilator drugs respond with an improvement dation of “elective” device therapy as a bridge to in symptoms and a resolution of the end-organ effects of transplantation. Most MCSD experience was gained the low cardiac output state, specifically improvements from implantation of devices in patients who were in renal or liver function. The failure to achieve these critically ill in the intensive care unit (ICU).
goals may be an indication for mechanical circulatorysupport.
4. MCSD AS DESTINATION THERAPY
For patients responsive to inotropic therapy, a period of slow weaning from inotropes is mandatory to reducethe potential need for long-term inotropic therapy.
1. Elective MCSD implant as destination therapy Failure to wean from inotropes may be defined as: should be considered in non-transplant candidates (a) recurrence of symptoms (shortness of breath refrac- who are dependent on long-term administration tory to diuretics, hypotension and/or hypoperfusion); of intravenous inotropes to maintain a stable state and/or (b) declining urinary output and a progressive 1. Despite the presence of a malignancy when a life 1. MCSD should be considered as a useful strategy to expectancy of Ͼ2 years is foreseeable, mechanical bridge patients to heart transplantation in those assistance may be considered as destination ther- patients who are otherwise not considered trans- plant candidates as a result of the degree andpersistence of pulmonary hypertension despite inotropic therapy (Level of Evidence: C ).
1. Metastatic tumors should be considered an abso- Background. High pulmonary vascular resistances limiting heart transplantation indication may persist under inotropic therapy. Completely unloading the left Background. The relevant issues for MCSD implanta- ventricle by MCSD implantation may lead to reversal of tion as a bridge to heart transplantation also apply to high-resistance pulmonary hypertension, allowing heart patients considered for destination therapy.
To define the non-transplant patient population that will benefit the most from elective LVAD therapy, it is 1. In challenging clinical cases, where it is hard to important to determine the prognosis of patients with discriminate between heart failure (HF) progres- advanced, refractory heart failure. The best description sion and the unfavorable effect of medical ther- of survival in this population is the analysis from the apy, it is reasonable to perform right-heart hemo- Randomized Evaluation of Mechanical Assistance in dynamic assessment to verify a patient’s volume Treatment of Chronic Heart Failure (REMATCH) clinical status and cardiac output in order to tailor inotro- trial, wherein patients were randomized to either med- pic drug dose if prolonged administration is being ical therapy or placement of a Thoratec HeartMate I considered (Level of Evidence: C ).
LVAD. Survival for patients on long-term inotropic 2. It is reasonable to consider right-heart hemody- therapy (n ϭ 91) was only 39% and 24% vs 60% and 49% namic assessment to demonstrate or to establish in the LVAD group, at 6 months and 12 months, an association of the clinical and biochemical respectively. In contrast, in patients with refractory markers with measured hemodynamic deteriora- heart failure who did not require long-term inotropic tion after withdrawal of inotropic therapy (Level therapy (n ϭ 38), survival at 6 and 12 months was 67% and 40%, respectively. Thus, the REMATCH data sup-port the premise that patients with refractory heart 3.1. Elective MCSD Therapy
failure, who are not on inotropic therapy, have survival Elective MCSD therapy has been performed with LVAD implantation in patients with severe functional impair- data refer to a population older (average age 68 years) ment despite maximum medical therapy, including than heart transplant candidates with severe heart inotropic support, but with a relatively stable status.
failure symptoms (NYHA Functional Class IV) and pro- This definition excludes patients receiving ventila- vide evidence from which recommendations can be tory support, ultrafiltration or percutaneous mechanical made for use of an LVAD as destination therapy.
The Journal of Heart and Lung Transplantation 5. NURSE AND SOCIAL WORKER MANAGEMENT
5.2. Social, Family, Religious and Personal
OF MCSD CANDIDATES
Issues Assessment
5.1. Nurse Nutritional Status
To help determine that patients receiving VAD therapy The impact of inadequate nutrition is crucial for MCSD have adequate family/social support, a detailed psychoso- implantation Cachexia (addressed earlier) is cial evaluation should be completed. This should be a strong independent risk factor in patients undergoing performed by social workers familiar with VAD therapy VAD placement as a bridge to In addition, and the heart transplant process. Patient and family/social implantation of an intracorporeal pump, such as the support should be involved in the evaluation, although the Thoratec HeartMate or Novacor LVS, can cause prob- patient may be too ill to play an active role in this process.
lems with persistent ileus and early satiety, which Demographic information should be obtained, includ- further limit the ability to improve nutrition. It is ing distance from home to transplant center and emer- recommended that a thorough nutritional evaluation be gency contacts. The names of the patient’s family and social supports should be obtained. Documentation of the The main goals of a pre-operative nutritional plan are to promote surgical wound-healing, optimize immune An evaluation of patient and family support and under- function, and improve the macro- and micronutrient standing of past medical history and the present medical situation should be obtained.This assessment may pro- protein stores also facilitates management of warfarin vide insight into the patient’s history of compliance.
therapy for patients on LVADs who require anti-coagu- Primary language and educational level should be lation. The following considerations should be included established to guide teaching. Perceptions about VAD therapy and transplantation should be explored. Data gathered yield important information that will identify 1. A thorough history should be taken of dietary potential barriers and will transfer to educational goals habits as well as an updated assessment of bowel motility. It should be documented if patients have Marital status and personal relationships should be a history of previous abdominal surgery or malab- assessed. This should include the length and quality of the 2. Pre-albumin, albumin and transferrin should be discussion of how difficult situations or problems were measured with weekly follow-up until nutritional handled in the past. Additional family/support systems should be established because the primary caregiver may 3. Work-up for diabetes (glycosylated hemoglobin [HbA ]) and tight control of blood sugar is The patient’s cultural background and religious beliefs should be obtained. Beliefs/background may provide an-other source of social support and may also alert the team of a patient’s wishes not to undergo particular treatments.
1. Consider formal nutritional consultation for those A complete assessment of the patient’s financial situa- patients who are significantly cachectic, obese, tion should also be performed. Insurance and prescription diabetic or have significant renal dysfunction.
coverage or a charity care initiative must be thoroughly 2. Supplement of micronutrients to include multivi- established to determine whether the patient has ade- tamin, folate, zinc sulfate and Vitamin C (the latter quate financial support to undergo VAD therapy and heart 3. Institute enteral feedings pre-operatively in se- End-of-life issues should be discussed with the patient and their social support before VAD implantation. Anadvanced directive or health-care proxy should be com- pleted if possible. Assessment of patient and social sup- 1. Measure C-reactive protein pre-operatively and at port should be ongoing, as stressors may change dynamics intervals post-operatively to monitor changes in and the willingness of family/friends to provide continued support. This should be done on a monthly basis or as 2. Indirect calorimetry or other metabolic studies should be done to better define caloric needs.
3. Institute parenteral nutrition if the enteral route is 6. WHEN AND HOW ULTRAFILTRATION TECHNIQUES
SHOULD BE USED
4. Continued follow-up with formal nutritional con- In patients with advanced NYHA Functional Class III sultation should be done as indicated.
and IV heart failure who are being considered or listed The Journal of Heart and Lung Transplantation for heart transplantation, the following recommenda- symptoms of cardiogenic shock; if intravevous pressors are required to maintain an adequateblood pressure; or there is end-stage renal disease 1. Intermittent hemodialysis should not be used for removal of excess fluid because large fluid shifts inshort periods of time may lead to hemodynamic 6.1. What is Ultrafiltration?
instability and worsening of the overall clinical Approved therapies for congestion in acute decompen- status. Intermittent hemodialysis should be insti- sated heart failure (ADHF) are simultaneously ineffec- tuted when patients meet criteria for end-stage tive and expensive. Mechanical fluid removal is a non- renal disease, in which case the severity of intrin- pharmacologic treatment for congestion.
sic kidney disease precludes consideration for Ultrafiltration is the passage of water and non– protein-bound small and medium-molecular-weight sol- 2. The role of peritoneal dialysis for short-term man- utes through a semi-permeable membrane when hydro- agement of refractory heart failure is limited to static pressure exceeds oncotic pressure. Oncotic situations in which extracorporeal ultrafiltration is pressure is determined by the concentration of proteins either impossible or unavailable. However, further in plasma. Hydrostatic pressure is determined by the investigation of the efficacy and safety of this blood pressure in the filtering device, generated by approach is needed before specific recommenda- either the patient’s blood pressure or by an extracor- tions can be made on the use of peritoneal dialysis poreal blood pump, plus the suction in the ultrafiltrate in patients with advanced heart failure.
compartment. The sum of these pressures generates the 3. Of the ultrafiltration approaches described, the transmembrane pressure that drives the plasma water most practical are veno-venous ultrafiltration tech- niques, in which isotonic plasma is propelled Hemofiltration is a blood-cleansing technique in through the filter by an extracorporeal pump.
which ultrafiltration occurs, but the ultrafiltrate is re- These approaches avoid arterial puncture, remove placed with clean fluid, which dilutes the concentration a predictable amount of fluid, are not associated with significant hemodynamic instability, and, inthe case of peripheral veno-venous ultrafiltration, 6.2. Clinical Methods of Ultrafiltration
do not require specialized dialysis personnel and 6.2.1. Intermittent hemodialysis. For intermittent
can be performed in an outpatient setting.
hemodialysis, access to the circulation is achieved with 4. Ultrafiltration techniques have been used in pa- either an arteriovenous fistula or with tunneled, cuffed tients with decompensated heart failure and vol- silicone catheters inserted percutaneously into the in- ume overload refractory to diuretic therapy. These ternal jugular vein. A 4-hour hemodialysis session can patients generally have pre-existing renal insuffi- lower BUN by 60%, remove 50 to 150 mEq of potas- ciency (calculated creatinine clearance 30 to 90 sium, and remove 3 liters of ultrafiltrate.
ml/min) and, despite daily oral diuretic doses, In patients with end-stage heart failure, hemodialysis develop signs of pulmonary and peripheral con- is the least tolerated form of dialysis, because large fluid gestion (jugular venous distention Ն7 cm, pulmo- shifts in a short period can lead to severe hemodynamic nary rales, paroxysmal nocturnal dyspnea or or- thopnea, peripheral edema [Ն2ϩ], enlarged liveror ascites, sacral edema). Ultrafiltration and tem- 6.2.2. Peritoneal dialysis. Peritoneal dialysis requires
porary cessation of diuretic may restore diuresis the delivery of a hypertonic substance (dextrose) into the peritoneal cavity. Water diffuses down its concen- 5. Based on the well-documented relationship be- tration gradient from the extracellular fluid spaces tween increases of RA pressure and reductions of bathing the peritoneal cavity into the hypertonic peri- glomerular filtration rate (GFR), as well as the toneal dialysate. This produces a net fluid loss into the diuretic-induced decrease of GFR, a strategy of temporarily holding diuretics and reducing vol- dialysate generates an ultrafiltration rate (UFR) of 800 ume excess with ultrafiltration may seem logical ml/hour. Use of less hypertonic dialysate or prolonga- tion of dwell time decreases UFR. With the currently 6. Patients should not be considered for ultrafiltra- available peritoneal dialysis solutions, UFR of 70 to 550 tion under any of the following conditions: ve- ml/hour can be achieved. Peritoneal dialysis can be nous access cannot be obtained; hematocrit is performed acutely or continuously for inpatients (con- Ն40%; there is a hypercoagulable state; systolic tinuous equilibration peritoneal dialysis [CEPD]) orblood pressure is Ͻ85 mm Hg or there are signs or outpatients (continuous ambulatory peritoneal dialysis The Journal of Heart and Lung Transplantation [CAPD]). Icodextrin-based solutions, which generate 6.2.5. Continuous ultrafiltration techniques. Tech-
sustained ultrafiltration over long dwell periods, are niques for continuous ultrafiltration include slow con- now being Advantages of peritoneal dialysis tinuous ultrafiltration (SCUF), continuous hemofiltra- include its low risk, wide availability and limited train- The main advantages of continuous veno-venous able response, slow ultrafiltration, mild discomfort, ultrafiltration with an extracorporeal blood pump are hydrothorax and relative contraindications (ileus, ab- achievement of constant blood flow and ultrafiltration dominal adhesions and incisions). Complications may rates and the hemodynamic stability afforded by iso- include respiratory compromise, impaired venous re- tonic ultrafiltration. Potential disadvantages include the turn, hypernatremia, hyperglycemia, peritonitis and need for central venous access or arterial puncture, the requirement for anti-coagulation, bleeding, hypovole-mia and the need for specialized dialysis 6.2.3. Intermittent isolated ultrafiltration. With in-
termittent isolated ultrafiltration (IIUF), a veno-venous
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