Results of a multicenter clinical trial with the Thoratec Implantable Ventricular Assist Device^⁎

Article Outline

• Abstract
• Materials and Methods
  • Device
  • Methods
  • Surgical Implantation
• Results
  • Baseline Demographics
  • Duration of Support
  • Functional Status
  • Survival
  • Adverse Events
• Discussion
• Acknowledgment
• Appendix E1. Study Inclusion Criteria
• References
• Copyright

Objective

The Thoratec Implantable Ventricular Assist Device (Thoratec Corporation, Pleasanton, Calif) can be used for univentricular or biventricular support in patients with a body surface area as low as 1.3 m². Results of the multicenter clinical trial are reviewed.

Methods

Between October 2001 and June 2004, a total of 39 patients at 12 institutions were supported with the Thoratec Implantable Ventricular Assist Device. Twenty-four patients (62%) received left ventricular assist devices and 15 (38%) received biventricular assist devices. Indications included bridge to transplantation (n = 30) and postcardiotomy failure (n = 9). The control group included 100 patients from the Food and Drug Administration approval submissions for the paracorporeal version of the ventricular assist device.

Results

Twenty-eight male and 11 female patients, with mean age of 48 years (16–71 years) and body surface area of 1.9 m² (1.3–2.4 m²) were supported for 3938 patient-days (10.8 patient-years). Mean left ventricular assist device flow index on the first postoperative day was 2.5 ± 0.5 L/(min·m²). Mean duration of support was 101 days (9–597 days). Eighteen patients were discharged after a mean duration of 96 days. There were no ventricular assist device failures. Complications included 13 cases of bleeding requiring reexploration (33.3%), 1 embolic and 2 hemorrhagic strokes (7.7%), 5 driveline infections (12.8%), and 2 pocket infections (5%). Support to successful outcomes was 70% for bridge to transplantation and 67% for postcardiotomy recovery, versus historical results for the paracorporeal ventricular assist device of 69% for bridge to transplantation and 48% for postcardiotomy recovery.

Conclusion

The Thoratec Implantable Ventricular Assist Device is a new implantable pulsatile ventricular assist device that allows hospital discharge for patients as a bridge to transplantation or for postcardiotomy failure. It is the first Food and Drug Administration–approved implantable ventricular assist device with biventricular capability.

CTSNet classification: 22, 27, 34

Abbreviations and Acronyms: BTT, bridge to transplantation, FDA, Food and Drug Administration, IVAD, implantable ventricular assist device, LVAD, left ventricular assist device, LVAS, left ventricular assist system, NYHA, New York Heart Association, PVAD, paracorporeal ventricular assist device, RVAD, right ventricular assist device, VAD, ventricular assist device

Considerable progress has been made during the last decades in the development of ventricular assist devices (VADs). Initially, failure to wean from cardiopulmonary bypass was the primary indication for VAD support.¹, ², ³, ⁴, ⁵ The roles of VADs and artificial hearts have expanded, however, to encompass support of patients awaiting cardiac transplantation⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹, ¹², ¹³ and destination therapy as an alternative to optimal medical management.¹⁴, ¹⁵, ¹⁶

The Thoratec Paracorporeal Ventricular Assist Device (PVAD; Thoratec Corporation, Pleasanton, Calif) is the mainstay of many mechanical circulatory support programs. Based on designs that date back to the 1970s,¹⁷ it was approved by the Food and Drug Administration (FDA) in 1995 for bridge to transplantation (BTT) and in 1998 for postcardiotomy myocardial recovery. As of Jan 2006, more than 3000 patients have been supported for both indications with the Thoratec PVAD. Although implantable electric left ventricular assist device (LVAD) systems are often selected for their wearable controllers and batteries, the PVAD’s simplicity, size, and biventricular capability make it the device of choice for many patients. As more patients have been supported with the PVAD for longer durations (longest: 3.3 years of biventricular support without changing pumps), however, a need has arisen for an implantable version to facilitate patient discharge from the hospital and potentially improve quality of life. In addition, because implantable electric LVAD systems have been designed solely for left ventricular support, there is a clinical need for implantable assist device options for patients with severe biventricular failure. The Thoratec Implantable Ventricular Assist Device (IVAD; Thoratec Corporation) was therefore developed, retaining as much in common with the PVAD system as possible. The system underwent a formal clinical trial and was FDA approved in 2004 on the basis of the results. This report provides the results of this clinical trial relative to a historical control group of patients with the Thoratec PVAD.

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Materials and Methods 

Device 

The Thoratec IVAD blood pump (Figure 1) was designed with incremental changes to the commercially available PVAD, facilitating implantation of the pump while retaining the basic flow path and pumping mechanisms.¹⁸, ¹⁹ The pump housing material was changed from polysulfone and stainless steel to a titanium alloy, and the Hall effect pump-full sensor was replaced with an infrared sensor to detect both pump full and pump empty. The cannulas were shortened and the driveline lengthened for implantability. No changes were made to the blood path geometry in the pump, and with the exception of the valve housings (changed from stainless steel to titanium alloy), the blood contacting materials are identical.

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• Figure 1. 

  Implantable ventricular assist device has same internal flow path as paracorporeal ventricular assist device, but plastic housing is replaced with smooth, contoured, polished titanium housing for improved implantability, and driveline is extended and covered with polyester velour as percutaneous lead.

The Thoratec IVAD was designed for preperitoneal placement and is pneumatically powered by an external portable TLC-II Driver. A single percutaneous lead for each VAD is used for pneumatic actuation and the sensor wires. Univentricular or biventricular support (Figure E1, A and B) is possible by using the appropriate atrial or ventricular inflow cannula and arterial outflow cannula. The IVAD, which weighs 339 g and has a displaced volume of 252 mL, is slightly smaller and lighter than the PVAD (weight 419 g, volume 318 mL) and can generate pulsatile flow up to 7.2 L/min.

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• Figure E1. 

  Implantable ventricular assist device is placed in preperitoneal position and is small enough to be used for univentricular (A) or biventricular (B) support. One percutaneous pneumatic driveline is tunneled for each ventricular assist device.

Methods 

The Thoratec IVAD was studied in a prospective, multicenter, nonrandomized clinical trial for use as a BTT or for patients in postcardiotomy recovery who cannot be weaned from cardiopulmonary bypass. A total of 39 patients were enrolled at 9 centers in the United States and 3 in Europe. The primary study objective was to evaluate the safety and effectiveness of the IVAD, as demonstrated by VAD flow index, survival, and adverse event rates, and to establish basic equivalence with the PVAD. Survival results and adverse events were compared with those among 100 patients in the original clinical trial of the PVAD for BTT and for postcardiotomy myocardial recovery.²⁰

Eligible patients were 12 to 70 years of age with acute or chronic heart failure necessitating VAD support to achieve adequate flow. Study inclusion criteria were similar to current indications for BTT or postcardiotomy failure and were met before patient enrollment (Appendix E1). Patients were excluded for any of the following reasons: active systemic infection, hemodialysis or hemofiltration requirements, intolerance to anticoagulation or antiplatelet therapy, chronic liver disease, elevated serum creatinine (>4 mg/dL) or total bilirubin (>3 mg/dL), recent pulmonary embolus, severe cerebrovascular disease, cardiopulmonary resuscitation on the way to the operating room, and concurrent mechanical support with any other circulatory support devices.

Adverse event definitions used were in compliance with FDA requirements at the time of the initiation of the clinical trial. Because the original PVAD trial used adverse event definitions different from those used in the IVAD trial, the original PVAD data were reviewed and reclassified according to the definitions of the IVAD trial.

The study was carried out under the regulations for investigational device exemption of the FDA. Informed consent was obtained before study participation. Each study site obtained institutional review board or ethics committee approval before study initiation, and any country-specific approval was obtained before patient enrollment.

Surgical Implantation 

The Thoratec IVAD was implanted through a standard median sternotomy approach. The pocket for the IVAD was developed below the left rectus muscle or between the left posterior rectus fascia and the peritoneum. The driveline was tunneled below the umbilicus and brought out the right midquadrant above the belt line. After heparinization, standard cardiopulmonary bypass was instituted. Generally, the inflow and outflow cannulas were inserted during cardiopulmonary bypass, with the heart decompressed and beating. Aortic crossclamping was not necessary, and left ventricular vents were used at the surgeon’s discretion. The 14-mm outflow graft was sewn to the ascending aorta on the greater curvature as an end-to-side anastomosis. Left ventricular apex cannulation was achieved in all patients with LVAD support. It was possible to cannulate the left atrium through the left atrial appendage or the right superior pulmonary vein with the atrial cannula for LVAD support. When a right ventricular assist device (RVAD) was necessary, the outflow graft was sewn as an end-to-side anastomosis to the pulmonary artery and the inflow cannula was inserted either into the right atrium or directly into the right ventricle. After connection of the inflow and outflow grafts to the pump, the patient was weaned from cardiopulmonary bypass and the heparin was fully reversed with protamine.

Patients were typically anticoagulated initially with heparin for the first or second postoperative day at a dosage of about 10 μg/(kg · min), gradually increasing to maintain a partial thromboplastin time of about 1.5 times control. Patients were switched to warfarin when able to tolerate oral medications at doses to keep the international normalized ratio at 2.5 to 3.5. Dextran, aspirin and dipyridamole were also used in some patients.

Statistical comparisons between groups were conducted with Fisher exact test for 2 × 2 categorical variables and an unpaired t test for continuous variables.

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Results 

Baseline Demographics 

A total of 39 patients were enrolled between October 2001 and June 2004. The baseline demographics were similar for the IVAD and PVAD cohorts (Table 1). The 28 men and 11 women ranged in age from 16 to 71 years (mean 48 years), had an average body surface area of 1.9 m² (1.3–2.4 m²), and an average weight of 75 kg (42–115 kg). Cardiac disease etiologies were ischemic (n = 13), idiopathic dilated cardiomyopathy (n = 18), other cardiomyopathy (n = 1 each for familial, viral, cocaine-induced, chemotherapy induced, and hypertrophic), myocarditis (n = 1), and unspecified (n = 2). Before implantation, 35 (90%) of the 39 patients were in New York Heart Association (NYHA) functional class IV, and all 39 patients had severely compromised hemodynamics (Table 1). Twenty-six patients had a history of arrhythmias, 8 had previous cardiac arrests, and 23 had previous cardiac surgery, automatic implantable cardioverter defibrillators, or biventricular pacers.

TABLE 1. Baseline demographic, hemodynamic, and laboratory values for implantable ventricular assist device and paracorporeal ventricular assist device groups

Parameter	IVAD	PVAD	P value
Demographics	n=39	n=100
Age (y)	48±14(16-71)	46±12(17-66)	.302
Weight (kg)	77±15(42-115)	76±18(40-127)	.906
Body surface area (m2)	1.91±0.23(1.31-2.40)	1.9±0.2(1.3-2.6)	.877
Male/female ratio	28:11(72%:28%)	77:23(77%:23%)	.518
Bridge to transplantation/postcardiotomy ratio	30:9(77%:23%)	71:29(71%:29%)	.532
Hemodynamics	n=39	n=100
Cardiac index (L/[min·m2])	1.8±0.5	1.4±0.6	.002
Left atrial pressure or pulmonary capillary wedge pressure (mm Hg)	26.5±7.2	28.2±7.7	.272
Right atrial pressure or central venous pressure (mm Hg)	16.3±7.0	17.7±7.2	.361
Mean arterial pressure (mm Hg)	69±14	61±12	.006
Systolic blood pressure (mm Hg)	92±19	76±15	<.0001
Mean pulmonary arterial pressure (mm Hg)	40±12	36±11	.187
Venous oxygen saturation (%)	61%±23%	ND	ND
Heart rate (beats/min)	98±17	ND	ND
Left ventricular ejection fraction (%)	16%±7%	21%±15%	.080
Laboratory values⁎	n = 30	n = 69
Serum creatinine (mg/dL)	1.4±0.6	1.5±0.6	.448
Blood urea nitrogen (mg/dL)	35.1±20.4	32.4±16.4	.487
Alanine aminotransferase (U/L)	273±541	ND
Aspartate aminotransferase (U/L)	150±339	270±936	.568
Total bilirubin (mg/dL)	2.1±2.8	1.6±1.0	.207
White blood cell count (103 cells/μL)	9.4±4.5	13.6±6.3	.001
Hematocrit (%)	32.5%±7.6%	33.2%±5.9%	.624

Values are mean ± SD, with range given in parentheses as appropriate. IVAD, Implantable ventricular assist device; PVAD, paracorporeal ventricular assist device; ND, not determined.

Indications for IVAD use were advanced heart failure requiring circulatory support as a BTT (n = 30) or postcardiotomy ventricular failure (n = 9) (Table 2). Concomitant procedures for the 9 postcardiotomy patients included coronary artery bypass grafting (n = 3), mitral valve repair (n = 3) or replacement (n = 1), aortic valve replacement (n = 1), and ventricular septal defect repair (n = 1). Twenty-four patients (62%) received isolated LVAD support and 15 patients (38%) received biventricular assist device (BVAD) support. In the IVAD study, a smaller percentage (38%) of patients received BVADs, compared with 64% of patients in the PVAD cohort (Table 2). For BTT, approximately half of the patients in the IVAD cohort received BVADs, whereas for postcardiotomy only 1 of 9 received a BVAD. Left ventricular apex cannulation was used in the IVAD study for all LVADs, and right atrial (n = 12) or right ventricular (n = 2) cannulation was used for RVAD support. One day after VAD implantation, the mean LVAD pump flow index was 2.5 ± 0.5 L/(min · m²), significantly increased from a mean preoperative cardiac index of 1.8 ± 0.5 L/(min · m²). At 60 days, resting LVAD flow index averaged 2.7 ± 0.3 L/(min · m²) (2.2-3.3 L/[min · m²]); pump flow averaged 5.2 ± 0.7 L/min (4.1-6.8 L/min). RVAD flow rates were slightly lower, averaging 2.1 ± 0.3 L/(min · m²) on the first postoperative day and remaining relatively stable thereafter.

TABLE 2. Percentages of patients receiving left ventricular and biventricular assist devices for implantable ventricular assist device and paracorporeal ventricular assist device groups divided by indication

	IVAD (n = 39)			PVAD (n = 100)
	BTT (n = 30)	PC (n = 9)	Total	BTT (n = 71)	PC (n = 29)	Total
Left ventricular assist device (No.)	16(53%)	8(89%)	24(62%)	22(35%)	14(48%)	36(36%)
Biventricular assist device (No.)	14(47%)	1(11%)	15(38%)	49(69%)	15(52%)	64(64%)
Support duration (d, mean and range)	108(9-597)	77(14-250)	101(9-597)	35(0-247)	12(0-80)	28(0-247)

IVAD, Implantable ventricular assist device; PVAD, paracorporeal ventricular assist device; BTT, bridge to transplantation; PC, postcardiotomy.

Duration of Support 

IVAD support duration for the 39 patients was 3938 patient-days (10.8 patient-years), with an average support time of 101 days (Table 2). The mean duration of support for the 30 patients supported for BTT was 108 days (9–597 days), and the mean duration for the postcardiotomy patients was 77 days (14–250 days). Lengths of support have increased since the PVAD trial, when the average durations were 35 days for BTT and 12 days for postcardiotomy recovery. Eighteen patients were discharged from the hospital with the IVAD system for a mean duration of 96 days (2–454 days). Forty-four percent of the total patient-days of support with the IVAD in the clinical trial were spent out of the hospital. Ten patients required 15 hospital readmissions, and an additional patient had 12 readmissions, for reasons including arrhythmias, pleural effusion and right heart failure, fever and dehydration, nose bleed, wound drainage, and neurologic symptoms.

Functional Status 

All discharged patients engaged in light-to-moderate physical activity after discharge, including walking, shopping, visiting family and friends, and entertainment. By week 8, 69% of the patients were in NYHA functional class I or II, a significant improvement from the 93% of patients in NYHA functional class IV before implantation. Average improvement was 1.8 functional classes, from an average of 3.9 at baseline to 2.1 at week 8.

Survival 

Twenty-seven of the 39 patients (69%) were successfully supported to cardiac transplantation or device removal for myocardial recovery (TABLE 3A, TABLE 3B), an overall survival similar to that in the PVAD trial and significantly better than the 0% survival in the non-VAD medically managed control group from the original PVAD study.²⁰ The postcardiotomy survival (67%) was similar to that for BTT (70%). One patient (3.3%) recovered ventricular function in the BTT arm and was weaned from the VAD, and 2 (22%) patients in the postcardiotomy arm received heart transplants, illustrating the challenge in identifying the ultimate patient outcome at the time of implantation. When divided into univentricular or biventricular IVAD support for BTT (Table 3B), 13 of the 16 patients receiving LVAD support (81%) and 8 of the 14 patients requiring BVAD support (57%) underwent transplantation or weaning. Twenty-two (81%) of the 27 patients who either underwent transplantation or were weaned from the device were alive 30 days after VAD removal. For postcardiotomy support, 6 (75%) of the 8 patients with LVAD support were weaned or underwent transplantation; the single patient with BVAD patient died. Twenty (91%) of the 22 patients who underwent cardiac transplantation were discharged alive from the hospital.

TABLE 3A. Outcomes for implantable ventricular assist device and paracorporeal ventricular assist device groups divided by indication

	IVAD			PVAD
	BTT	PC	Total	BTT	PC	Total
Implanted	30	9	39	71	29	100
Survived	21(70.0%)	6(66.7%)	27(69.2%)	49(69.0%)	14(48.3%)	63(63.0%)
Weaned	1(3.3%)	4(44.4%)	5(12.8%)	0	14(48.3%)	14(14.0%)
Transplanted	20(66.7%)	2(22.2%)	22(56.4%)	49(69.0%)	0	49(49.0%)
Died on device	9(30.0%)	3(33.3%)	12(30.8%)	22(31.0%)	15(51.7%)	51(51.0%)

IVAD, Implantable ventricular assist device; PVAD, paracorporeal ventricular assist device; BTT, bridge to transplantation; PC, postcardiotomy.

TABLE 3B. Bridge to transplantation outcomes for implantable ventricular assist device and paracorporeal ventricular assist device groups requiring left ventricular and biventricular assist devices

	IVAD			PVAD
	LVAD	BVAD	Total	LVAD	BVAD	Total
Implanted	16	14	30	71	29	100
Survived	13(81.3%)	8(57.1%)	21(70.0%)	49(69.0%)	14(48.3%)	63(63.0%)
Weaned	0(0.0%)	1(7.1%)	1(3.3%)	0	14(48.3%)	14(14.0%)
Transplanted	13(81.3%)	7(50.0%)	20(66.7%)	49(69.0%)	0	49(49.0%)
Died on device	3(18.7%)	6(42.9%)	9(30.0%)	22(31.0%)	15(51.7%)	51(51.0%)

IVAD, Implantable ventricular assist device; PVAD, paracorporeal ventricular assist device; LVAD, left ventricular assist device; BVAD, biventricular assist device.

Adverse Events 

Seventy-nine percent of the adverse events occurred within 30 days of implantation, with most occurring while the patient was hospitalized. Adverse event rates for the IVAD were generally less than or comparable to those for the PVAD (Table 4). Infection accounted for most IVAD adverse events, with 42 events in 22 patients. There were 5 patients with driveline infections and 2 with pump pocket infections. Thirty-four of the 42 events were local infections, and the remaining 8 events were systemic. All infections were treated with antibiotics. Of the 18 patients (46%) with bleeding events, 42% occurred within 1 day of IVAD implantation. A single patient with severe hepatic dysfunction accounted for 28% of all bleeding events. Twenty-one neurologic events (including stroke, transient ischemic attack, encephalopathy, and peripheral weakness) occurred in 14 patients, of which 57% (12/21) were transient ischemic attacks in 8 patients that resolved within 24 hours. Three patients had moderate to severe stokes: 1 patient had occipital infarctions on days 18 and 24, and 2 patients had intracranial bleeding after days 53 and 87 that resulted in death. An additional patient fell while exercising, had a subdural hematoma develop, and died. The percentages of patients with ischemic or hemorrhagic stroke were 7.7% (3/39) for the IVAD cohort and 12.0% (12/100) for the PVAD cohort. The percentages of patients with transient ischemic attack were 20.5% (8/39) for the IVAD cohort and 5.0% (5/100) for the PVAD cohort. Reoperations were required in 54% (21/39) of the IVAD cohort and in 48% (48/100) of the PVAD cohort. Thirteen of these 21 patients with IVADs underwent exploration for bleeding or for cardiac tamponade within the first few days. Five reoperations were required to correct IVAD problems (2 reoperations to improve the pump pocket in 1 patient, 1 reoperation to reposition the VAD to correct a kink in the cannulas, 1 reoperation to replace the inflow cannula, and 1 reoperation to inspect the operation of the IVAD inflow valve). One patient with LVAD support received a paracorporeal RVAD on postoperative day 16 and underwent transplantation 63 days later. This patient was included in the analysis as receiving a BVAD.

TABLE 4. Adverse event rates for implantable ventricular assist device and paracorporeal ventricular assist device groups

	IVAD (n = 39)	PVAD (n = 100)	Risk ratio (95% confidence interval)
Cumulative patient-days of support	3938	2857
Infection	0.32	0.61	0.53(0.35-0.78)
Bleeding	0.27	0.66	0.41(0.27-0.63)
Neurologic dysfunction	0.16	0.43	0.37(0.22-0.63)
Hepatic dysfunction	0.11	0.69	0.16(0.09-0.29)
Arrhythmias	0.09	0.23	0.40(0.20-0.80)
Respiratory failure	0.09	0.15	0.62(0.29-1.35)
Pleural effusion	0.09	0.11	0.87(0.38-2.02)
Renal failure	0.08	0.21	0.36(0.17-0.78)
Cardiac tamponade	0.07	0.05	1.31(0.44-3.90)
Hemolysis	0.02	0.07	0.21(0.04-1.00)
Peripheral thromboembolism	0.02	0.16	0.10(0.02-0.42)
Right heart failure	0.01	0.09	0.08(0.01-0.64)

Rates are events per 30 patient-days.

Renal dysfunction occurred in 10 patients (26%), and hepatic dysfunction occurred in 14 patients (36%). Renal and hepatic function improved during IVAD support, as evidenced by changes in creatinine, blood urea nitrogen, and alanine aminotransferase. Patients who required BVADs had higher preoperative values than did patients who required only LVAD support, and their values remained elevated longer before improving to the normal range.

There were no serious IVAD failures, and no IVADs required replacement. There were 10 pump or cable malfunctions related to the loss of pump full or empty signals from the device. Patients with loss of the full signal had the system managed in fixed rate mode rather than automatic rate mode without consequence. There were 10 patients with battery, charger, or driver malfunctions, including excess noise or nuisance alarms. One driveline was noted to be broken during explantation, and 2 instances of kinked cannulas were reported.

There were 2 perioperative deaths (9%) after transplantation, 1 from right ventricular failure and pulmonary edema and 1 from multiorgan failure. Two patients weaned from IVAD support after postcardiotomy ventricular failure died before discharge from gangrenous bowel or multiple organ failure. Twelve patients died while supported by the device, 7 from multiple organ failure in the first 2 to 5 weeks, 2 from hemorrhagic cerebrovascular accident, 2 from sepsis, and 1 from a subdural hematoma after a fall while at home.

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Discussion 

The results from this clinical trial demonstrate that the IVAD, an implantable version of the Thoratec PVAD system, has comparable survival and reduced complication rates relative to the PVAD and provides an additional option for patients with advanced heart failure who required support as a BTT or pending recovery of the native heart. All patients received sufficient blood flow to restore hemodynamic values. Major organ function improved, and stable pulsatile circulatory support was provided by the IVAD for as long as 18 months. There were significant improvements in patient functional status, with more than two thirds of patients in NYHA functional class I or II by the 8th week of support. Patients were successfully discharged from the hospital and were active until transplantation or cardiac recovery. This is the first successful clinical trial of an implantable circulatory support system providing biventricular assistance.

In this study, 70% of the combined LVAD and BVAD subgroups of patients treated with the IVAD for BTT had successful weaning or transplantation, an outcome similar to those reported in other multicenter BTT clinical trials, including those of the Thoratec PVAD (69%),²⁰ the HeartMate IP LVAD (71%),⁶ the HeartMate VE Left Ventricular Assist System (LVAS, 71%),¹⁰ the Novacor LVAS (78%),¹¹ and the Cardiowest Total Artificial Heart (79%).¹³ Patients who received the IVAD for isolated left ventricular support had an 81% survival to cardiac transplantation. Patients who required biventricular support had lower survival (57%), consistent with previous studies demonstrating that patients with increased severity of illness, especially with renal and hepatic failure, are more likely to require BVADs and thus be at higher risk for death than patients supported with isolated LVADs.⁷, ²¹, ²⁴ In previous studies, one center reported using Thoratec BVADs for all of their patients with good results,²² whereas other single centers with more than 100 implants with the Thoratec VAD have reported 30% to 50% of patients treated as BTT receiving BVADs.⁸, ²³, ²⁴ These percentages, with patients selected because of the device’s biventricular capability, are typically higher than the 7% to 15% incidence of RVAD use in the clinical experience of implantable electric LVADs,⁹, ¹⁰, ¹¹, ¹² with patients selected with the goal of univentricular support. Improved patient selection and earlier implantation remain the key factors that could reduce the 25% to 35% mortality among patients who do not survive to transplantation with the use of any VAD.

All adverse events reported in the trial were anticipated, and most occurred within the first 30 days after implantation. This is consistent with findings reported in the previous Thoratec PVAD and HeartMate LVAS studies. Only 1 patient had an embolic stroke and 2 had hemorrhagic strokes during IVAD support, and there were no device failures. Infection remains a concern for patients receiving any LVAD system and accounted for most adverse events; device-related infections were limited in the IVAD study to 2 pocket infections and 5 driveline infections, however, and sepsis was reported as the cause of death in only 2 cases.

One recognized limitation of the IVAD study was that it used a historical control group from the original clinical trial of the PVAD for comparisons of outcomes and adverse events. Clearly, patient management has changed since that study was conducted more than a decade ago, which could have an effect on detailed comparisons between these groups. The PVAD cohort is a suitable comparison group, however, in that the design and intended use of the PVAD and IVAD are similar, both pumps use the same pneumatic power sources, and both trials used similar inclusion and exclusion criteria to enroll patients. Thus no concurrent control group was deemed necessary to establish the basic equivalence of the IVAD with the PVAD.

The selection process regarding which device is best suited for a given patient and when the IVAD would be the appropriate choice is becoming more complex, especially with the emergence of the newer continuous-flow LVADs, which also address the need for smaller devices. For those programs that are not able to keep multiple devices on the shelf or for centers with existing experience with the PVAD, the IVAD seems like a logical choice because of its versatility and use for both BTT and postcardiotomy shock. The IVAD would also be an appropriate option for patients with a high likelihood of needing biventricular support.

The principal need for an option for implantation of the Thoratec IVAD is to facilitate hospital discharge, improve postoperative management, and help patients with psychosocial issues and acceptance of the device. Although patients with PVADs can be and are now being discharged from the hospital,²⁵ in many cases implantation may be preferable for long-term support and for outpatient management. Paracorporeal placement is preferable for short-term support, for example for less than 30 days, and for smaller patients²⁶ and those with other anatomic placement issues. Although implantable rotary pumps are showing much promise as small and quiet alternatives to the large first-generation electric LVADs, the IVAD is the smallest and lightest pulsatile VAD and has less motion and a smaller driveline than the currently available electric pulsatile LVADs. On the other hand, electric LVADs have the advantage of wearability and may be preferable for large patients who need long-term support, so long as it is known that only left ventricular support will be required. It is generally believed that smaller devices with less motion and smaller, more flexible drivelines will result in fewer infections and greater ease of outpatient management. Although these long sought after clinical benefits from smaller devices were not clearly demonstrated in this initial pilot study, it is to be hoped that they will be seen with increased use and continued improvements in patient management.

The Thoratec IVAD has demonstrated the capability of providing univentricular and biventricular support in a wide range of patients with a body surface area as small as 1.3 m². Long-term cardiac support was provided for as long as 597 days, and patients were successfully discharged from the hospital to await cardiac transplantation or myocardial recovery. The IVAD operated reliably, and there were no reported device failures. The results of this study establish the Thoratec IVAD as a viable option for patients with end-stage heart failure.

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The coauthors acknowledge the other IVAD Study Group Members: Nelson A. Burton, MD, Inova Fairfax Hospital, Annandale, Va; Kathy Magliato, MD, Cedars Sinai Medical Center, Los Angeles, Calif; James C. Spann, MD, St Francis Hospital, Tulsa, Okla; Olivier Bastien, MD, PhD, Hospices Civils de Lyon, Lyon, France; and Jack Copeland, MD, University of Arizona, Tucson, Ariz.

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Appendix E1. Study Inclusion Criteria 

To be enrolled, the patient had to meet criteria 1 and 2 and either 3 or 4:

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