Margaret Flannery

Low Incidence of Myocardial Recovery After Left Ventricular Assist Device Implantation in Patients With Chronic Heart Failure

BACKGROUND Mechanical, histological, and biochemical improvement has been described in patients after left ventricular assist device (LVAD) support. Explantation of the LVADs without heart transplantation has been described in selected patients who received this therapy as a bridge to transplantation. METHODS AND RESULTS A retrospective review of patients receiving a mechanical bridge to transplantation at Columbia Presbyterian Hospital after July 21, 1991, was performed to determine the incidence of patients in whom the device was successfully explanted. From August 1, 1996, to February 1, 1998, we prospectively attempted to identify potential explant candidates by the use of exercise testing. During this time, we recruited 39 consecutive patients after insertion of the Thermo Cardiosystems vented electric device to participate in the following study. Approximately 3 months after device implantation, a maximal exercise test with hemodynamic monitoring and respiratory gas analysis was performed with the LVAD in the automated mode. The electric device was interfaced with a pneumatic console such that the rate could be decreased to 20 cycles/min. Hemodynamic measurements were recorded as the device rate was decreased. A repeat exercise test was then performed if the patient remained hemodynamically stable. A retrospective chart review of 111 LVAD recipients at our institution identified only 5 successful explant patients. Eighteen of the 39 patients were studied. Fifteen patients exercised with maximal device support. At peak exercise, VO2 averaged 14.5+/-3.6 mL. kg-1. min-1; LVAD flow, 8.0+/-1.3 L/min; Fick cardiac output, 11.4+/-3.3 L/min; and pulmonary capillary wedge pressure, 13+/-4 mm Hg. Seven patients remained normotensive and could exercise at a fixed rate of 20 cycles/min. In these patients, peak VO2 declined from 17.3+/-3.9 to 13.0+/-6.1 mL. kg-1. min-1. In one of these patients, the device was explanted. CONCLUSIONS Significant myocardial recovery after LVAD therapy in patients with end-stage congestive heart failure occurs in a small percentage of patients. Most of these patients have dilated cardiomyopathy. Exercise testing may be a useful modality to identify those patients in whom the device can be explanted.

Right ventricular dysfunction and organ failure in left ventricular assist device recipients: a continuing problem

BACKGROUND Although right ventricular assist device (RVAD) use has declined with the introduction of inhaled nitric oxide and phosphodiesterase inhibitors (type III), right ventricular dysfunction (RVD) is still a serious problem in patients receiving left ventricular assist devices (LVAD). METHODS We retrospectively analyzed Thoratec Vented Electrical LVAD recipients between June 1996 and September 1999. RVD was defined as inotropic requirement 14 days or more or need for RVAD postoperatively, or both. RESULTS Sixty-nine LVAD recipients were analyzed. Twenty-one patients (30.4%) had RVD, with 1 patient requiring RVAD insertion, and there were 48 non-RVD patients. There were no significant differences between both groups for age, sex, etiology of congestive heart failure, days of support, and preoperative hemodynamics. Preoperative right ventricle stroke work index (mm Hg x m(-2) x L(-1)) had a trend toward being lower in the RVD group (4.1+/-3.2 versus 6.1+/-3.7, p = 0.06). A higher preoperative total bilirubin (mg/dL) was noticed in the RVD group (4.0+/-5.2 versus 2.1+/-1.7). The RVD group had a higher postoperative creatinine (2.2+/-1.4 mg/dL versus 1.5+/-0.8 mg/dL), incidence of continuous venovenous hemofiltration dialysis (73% versus 26%), transfusion of packed red blood cells (43.2+/-28.6 units versus 24.7+/-18.9 units), platelets (58.6+/-46.1 units versus 30.2+/-20.4 units), with longer intensive care unit length of stay (33.6+/-34.7 days versus 9.1+/-6.9) and higher mortality (42.8% versus 14.5%). When deaths were excluded, both intensive care unit and postoperative length of stay were significantly longer in the RVD group. CONCLUSIONS RVD in LVAD recipients remains poorly identified and is associated with a high transfusion rate and end organ failure that results in increased intensive care unit and hospital length of stay, and a high mortality rate. Preoperative identification of risk factors for RVD may select patients who would benefit from a biventricular assist device and prevent the subsequent end organ failure.

Development of a Novel Echocardiography Ramp Test for Speed Optimization and Diagnosis of Device Thrombosis in Continuous-Flow Left Ventricular Assist Devices: The Columbia Ramp Study

OBJECTIVES This study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions. BACKGROUND In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test. METHODS We devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patients left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated. RESULTS Fifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope >-0.16. CONCLUSIONS Ramp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients.

Activation-induced T-cell death and immune dysfunction after implantation of left-ventricular assist de vice

BACKGROUND Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist devices (LVADs) are currently under investigation as permanent therapy for end-stage heart failure, but long-term successful device implantation is limited because of a high rate of serious infections. To examine the relation between LVAD-related infection and host immunity, we investigated immune responses in LVAD recipients. METHODS We compared the rate of candidal infection in 78 patients with New York Heart Association class IV heart failure who received either an LVAD (n=40) or medical management (controls, n=38). Fluorochrome-labelled monoclonal antibodies were used in analyses of T-cell phenotype. Analysis of T-cell function included intradermal responses to recall antigens and proliferative responses after stimulation by phytohaemagglutinin, monoclonal antibodies to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vivo by annexin V binding, and confirmed the result by assessment of DNA fragmentation. Activation-induced T-cell death was measured after T-cell stimulation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation. Between-group comparisons were by Kaplan-Meier actuarial analysis and Students t test. FINDINGS By 3 months after implantation of LVAD, the risk of developing candidal infection was 28% in LVAD recipients, compared with 3% in controls (p=0.003). LVAD recipients had cutaneous anergy to recall antigens and lower (<70%) T-cell proliferative responses than controls after activation via the T-cell receptor complex (p<0.001). T cells from LVAD recipients had higher surface expression of CD95 (Fas) (p<0.001) and a higher rate of spontaneous apoptosis (p<0.001) than controls. Moreover, after stimulation with antibodies to CD3, CD4 T-cell death increased by 3.2-fold in LVAD recipients compared with only 1.2-fold in controls (p<0.05). INTERPRETATION LVAD implantation results in an aberrant state of T-cell activation, heightened susceptibility of CD4 T cells to activation-induced cell death, progressive defects in cellular immunity, and increased risk of opportunistic infection.

Implantable Left Ventricular Assist Devices Provide an Excellent Outpatient Bridge to Transplantation and Recovery

OBJECTIVES Our recent experience with outpatient left ventricular assist device (LVAD) support is presented to demonstrate the possibilities and limitations of long-term outpatient mechanical circulatory assistance. BACKGROUND The experience with inpatient LVAD support as a bridge to transplantation has proved the efficacy of such therapy in improving circulatory hemodynamic status, restoring normal end-organ function and facilitating patient rehabilitation. With miniaturization of the power supplies and controllers, such mechanical circulatory support can now be accomplished in an outpatient setting. METHODS Between March 1993 and February 1997, 32 patients (26 male, 6 female, mean [+/-SEM] age 49 +/- 15 years) underwent implantation of the ThermoCardiosystems (TCI) Heartmate vented electric (VE) LVAD. The VE LVAD is powered by batteries worn on shoulder holsters and is operated by a belt-mounted system controller, allowing unrestricted patient ambulation and hospital discharge. RESULTS Mean duration of support was 122 +/- 26 days (range 3 to 605), with a survival rate to transplantation or explantation of 78%. Nineteen patients were discharged from the hospital on mean postoperative day 41 +/- 4 (range 17 to 68), for an outpatient support time of 108 +/- 30 days (range 2 to 466). Four patients underwent early transplantation and could not participate in the discharge program, and three patients currently await discharge. The complication rate was not statistically different from that encountered in our previous 52 patients with a pneumatic LVAD. CONCLUSIONS Outpatient LVAD support is safe and provides improved quality of life for patients awaiting transplantation. Wearable and totally implantable LVADs should be studied as permanent treatment options for patients who are not candidates for heart transplantation.

Comparison of Exercise Performance in Patients With Chronic Severe Heart Failure Versus Left Ventricular Assist Devices

BACKGROUND Left ventricular assist devices (LVADs) are frequently used as a bridge to cardiac transplantation and may be useful as long-term therapy. The purpose of this study was to compare the exercise performance of LVAD patients with that of ambulatory heart failure patients. METHODS AND RESULTS Exercise testing with hemodynamic and respiratory gas measurements was performed in 65 congestive heart failure (CHF) patients (age 53+/-10 years) and 20 LVAD patients (age 49+/-8 years). Peak Vo2 was significantly higher in the LVAD than the CHF patients (CHF, 12+/-3; LVAD, 15. 9+/-3.8 mL . kg-1 . min-1; P<0.001), as was the Vo2 at the anaerobic threshold (CHF, 8.1+/-2.1; LVAD, 12.2+/-2.9 mL . kg-1 . min-1; P<0.001). At rest, mean arterial blood pressure (CHF, 87+/-11; LVAD, 94+/-9 mm Hg) and cardiac output (CHF, 4+/-1; LVAD, 4. 9+/-0.9 L/min) were increased, whereas mean pulmonary artery pressure (CHF, 28+/-11; LVAD, 18+/-4 mm Hg) and pulmonary artery wedge pressure (CHF, 16+/-10; LVAD 5+/-3 mm Hg) were reduced (all P<0.01). At peak exercise, heart rate (CHF,125+/-24; LVAD, 148+/-24 bpm), blood pressure (CHF, 87+/-14; LVAD,96+/-12 mm Hg), and cardiac output (CHF, 7.6+/-2.2; LVAD, 11.2+/-2.6 L/min) were higher (all P<0. 01), whereas mean pulmonary artery pressure (CHF, 48+/-12; LVAD, 30+/-5 mm Hg) and mean pulmonary capillary wedge pressure (CHF, 31+/-11; LVAD, 14+/-6 mm Hg) were lower in the LVAD group (both P<0. 001). In the LVAD patients, Fick cardiac output was higher than LVAD flow sensor value measurements (Fick, 11.6+/-2.5; LVAD, 8.1+/-1.2 L/min; P<0.001). CONCLUSIONS Hemodynamic measurements at rest and during exercise are significantly improved in patients with devices compared with those in ambulatory heart failure patients awaiting cardiac transplantation. Similarly, the exercise capacity of device patients is better than that of transplant candidates and in the majority of patients is similar to that of patients with mild CHF.

Implantable left ventricular assist devices can successfully bridge adolescent patients to transplant

BACKGROUND Left ventricular assist devices (LVAD) have been used successfully as a life-sustaining bridge to transplantation in adults with end-stage heart failure. Long-term implantable cardiac assist devices for smaller adolescent patients are not yet available in the United States. METHODS This study reviews the experience with patients less than 21 years old that received HeartMate LVADs (TCI) at our institution. Twelve patients were implanted with 13 LVADs. The patients ranged in age from 11 to 20 years (mean 16 years). Body surface area ranged from 1.4 to 2.2 m2 (mean 1.8 m2). Patients were selected for LVAD placement based on eligibility for heart transplant and evidence of end-organ dysfunction. Device placement in small patients was facilitated with prosthetic graft abdominal wall closure. No patient received systemic anticoagulation. RESULTS The duration of LVAD support ranged from 0 to 397 days (mean 123 days). Seven of the 8 patients eligible for discharge from the hospital with a vented-electric LVAD were supported at home while awaiting transplantation. Outcomes of LVAD support were: LVAD explantation in 2 cases (15%), expiration with LVAD in place in 3 cases (23%), and successful transplantation in 8 cases (62%). Complications included 4 patients with systemic infection, 3 re-operations for hemorrhage, 1 embolic event, and 1 intraoperative air embolus that proved fatal. One explanted patient required a subsequent LVAD and the other expired 4 months after explantation. Six of the 8 transplanted patients are alive and well with follow-up ranging from 8 to 43 months. CONCLUSIONS Adolescent patients with heart failure can be successfully supported on a long-term basis to heart transplantation with the HeartMate LVAD. The wearable device allows for discharge home while awaiting transplantation. Device explantation without subsequent transplantation can be unpredictable. The incidence of thromboembolism remains low despite the absence of systemic anticoagulation. The technique of prosthetic graft closure of the abdominal wall facilitates the use of this device in smaller patients.

Improved survival rates support left ventricular assist device implantation early after myocardial infarction

OBJECTIVES Implantation of left ventricular assist devices (LVADs) early after acute myocardial infarction (MI) has traditionally been thought to be associated with high mortality rates due to technical limitations and severe end-organ dysfunction. At some experienced centers, doctors have refrained from earlier operation after MI to allow for a period of hemodynamic and end-organ stabilization. METHODS We retrospectively investigated the effect of preoperative MI on the survival rates of 25 patients who received a Thermocardiosystems Incorporated LVAD either <2 weeks (Early) (n = 15) or >2 weeks (Late) (n = 10) after MI. Outcome variables included perioperative right ventricular assistance (and right-sided circulatory failure), hemodynamic indexes, percent transplanted or explanted, and mortality. RESULTS No statistically significant differences were demonstrated between demographic, perioperative or hemodynamic variables between the Early and Late groups. Patients in the Early group demonstrated a lower rate of perioperative mechanical right ventricular assistance, but had a higher rate of perioperative inhaled nitric oxide use. In addition, 67% of patients in the Early group survived to transplantation and 7% to explantation, findings comparable to those in the Late group (60% and 0% respectively). CONCLUSIONS This clinical experience suggests that patients may have comparable outcomes whether implanted early or late after acute MI. These data therefore support the early identification and timely application of this modality in post-MI LVAD candidates, as this strategy may also reveal a subgroup of patients for whom post-MI temporary LVAD insertion may allow for full ventricular recovery.

Improved survival in patients with acute myocarditis using external pulsatile mechanical ventricular assistance

BACKGROUND Acute myocarditis remains a disease with a variable clinical course, from full ventricular recovery to complete heart failure; to date, few cases have been reported that describe the efficacy of temporary mechanical ventricular assistance for its treatment. METHODS We evaluated the voluntary world registry with the use of an external pulsatile ventricular assist device (the ABIOMED BVS 5000 [BVS]) for acute myocarditis to determine the impact of mechanical ventricular assistance on outcome. Variables analyzed included patient demographics, serum chemistries, and overall hemodynamics prior to BVS, while on BVS support, and after BVS explanation. Postoperative parameters included re-operation, bleeding, respiratory failure, renal failure, and infections, neurologic, or embolic events. RESULTS Eighteen patients in the ABIOMED world registry underwent BVS implantation for myocarditis; 11 (61.1%) had complete pre-operative and hemodynamic data for analysis. Patients were supported for 13.2 +/- 17.0 days, after which time 7 (63.6%) patients survived to explanation of the device and 2 (18.2%) underwent transplantation. Elevated admission serum chemistries (blood ureanitrogen [BUN], creatinine, transaminases) and hemodynamics (central venous pressure [CVP], mean pulmonary arterial pressure [PAP], pulmonary capillary wedge pressure [PCW], cardiac index [CI], all normalized during the period of device support. Estimated ejection fractions in the 7 explanted patients ranged between 50 to 60% at routine evaluation 3 years after device removal. CONCLUSIONS Temporary mechanical ventricular assistance represents an efficacious therapy for acute myocarditis in patients with hemodynamic decompensation despite maximal medical therapy. Failure to achieve full ventricular recovery while on device support still allows for other surgical alternatives, including implantation of a long-term implantable ventricular assist device, or cardiac transplantation.

Validity and Reliability of a Novel Slow Cuff-Deflation System for Noninvasive Blood Pressure Monitoring in Patients With Continuous-Flow Left Ventricular Assist Device

Background—Doppler ultrasound is the clinical gold standard for noninvasive blood pressure (BP) measurement among continuous-flow left ventricular assist device patients. The relationship of Doppler BP to systolic BP (SBP) and mean arterial pressure (MAP) is uncertain and Doppler measurements require a clinic visit. We studied the relationship between Doppler BP and both arterial-line (A-line) SBP and MAP. Validity and reliability of the Terumo Elemano BP Monitor, a novel slow cuff-deflation device that could potentially be used by patients at home, were assessed. Methods and Results—Doppler and Terumo BP measurements were made in triplicate among 60 axial continuous-flow left ventricular assist device (HeartMate II) patients (30 inpatients and 30 outpatients) at 2 separate exams (360 possible measurements). A-line measures were also obtained among inpatients. Mean absolute differences (MADs) and correlations were used to determine within-device reliability (comparison of second and third BP measures) and between-device validity. Bland–Altman plots assessed BP agreement between A-line, Doppler BP, and Terumo Elemano. Success rates for Doppler and Terumo Elemano were 100% and 91%. Terumo Elemano MAD for repeat SBP and MAP were 4.6±0.6 and 4.2±0.6 mm Hg; repeat Doppler BP MAD was 2.9±0.2 mm Hg. Mean Doppler BP was lower than A-line SBP by 4.1 (MAD=6.4±1.4) mm Hg and higher than MAP by 9.5 (MAD=11.0±1.2) mm Hg; Terumo Elemano underestimated A-line SBP by 0.3 (MAD=5.6±0.9) mm Hg and MAP by 1.7 (MAD=6.0±1.0) mm Hg. Conclusions—Doppler BP more closely approximates SBP than MAP. Terumo Elemano was successful, reliable, and valid when compared with A-line and Doppler.