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Biomedical subjects

Timothy J Myers

Publications and source records attributed to Timothy J Myers.

At least 19 recordsLinked to original sources
PubMed2006

Reversal of myocyte hypertrophy by ventricular unloading: cardiac improvement without adrenergic receptor up-regulation and relocalization.

In previous studies, we found that the improved contractile ability of cardiac myocytes from patients who have had left ventricular assist device (LVAD) support was due to a number of beneficial changes, most notably in calcium handling (increased sarcoplasmic reticulum calcium binding and uptake), improved integrity of cell membranes due to phospholipid reconstruction (reduced lysophospholipid content), and an upregulation of adrenoreceptors (increased adrenoreceptor numbers). However, in the case presented here, there was no increase in adrenoreceptor number, which is something that we usually find in core tissue at the time of LVAD removal or organ transplantation; also, there was no homogeneous postassist device receptor distribution. However, the patient was well maintained for 10 months following LVAD implantation, until a donor organ was available, regardless of the lack of adrenoreceptor improvement. We conclude from these studies that cardiac recovery is the result of the initiation of multiple repair mechanisms, and that the lack of expected changes, in this case increased adrenoreceptors, is not always an accurate indicator of anticipated outcome. We suggest that interventions and strategies have to consider multiple, beneficial changes due to unloading and target a number of biochemical and structural areas to produce improvement, even if not all of these improvements occur.

Humans↗
PubMed2006

Is native aortic valve commissural fusion in patients with long-term left ventricular assist devices associated with clinically important aortic insufficiency?

BACKGROUND: Long-term left ventricular assist device (LVAD) support diminishes flow through the native aortic valve and decreases valve motion. This may cause aortic valve commissural fusion. The clinical importance of such fusion is not well understood. METHODS: Thirty-three consecutive patients receiving long-term LVAD support were followed up until transplantation or death. In each case, the native aortic valve was examined pathologically for commissural fusion. Pathology findings were correlated with hemodynamic performance as assessed by both LVAD pump flow and echocardiography. RESULTS: Seventeen of the 33 patients had some degree of native aortic valve commissural fusion. Four patients had fusion at 2 commissures; of these, 2 had clinically significant native valve aortic insufficiency (2+ or greater), and 1 exhibited trace insufficiency of the native aortic valve. Thirteen patients had fusion at only 1 aortic commissure; of these, 2 had clinically significant aortic insufficiency (2+ or greater), and 3 had trace or mild (1+) insufficiency of native aortic valve. Two of the 4 patients with fusion at 2 commissures required increased LVAD support of >3 liters/min/cm2. No patient with fusion of only 1 commissure required increased LVAD support. Three patients with no commissural fusion of the aortic valve required increased LVAD support secondary to sepsis. CONCLUSIONS: Commissural fusion of the native aortic valve occurs in a significant number of patients receiving long-term LVAD support and can necessitate increased levels of LVAD support. Recognition of this phenomenon may allow development of strategies to minimize commissural fusion and extend LVAD pump life.

Adult↗
PubMed2006

Hemodynamics and patient safety during pump-off studies of an axial-flow left ventricular assist device.

BACKGROUND: Axial-flow left ventricular assist devices (LVADs), when inactivated, may result in regurgitant blood flow. We assessed the effects of regurgitant pump flow with the intraventricular Jarvik 2000 Heart LVAD (Jarvik Heart, Inc., New York, NY) on hemodynamics and patient safety under pump-off conditions. METHODS: Thirty patients being supported by a Jarvik 2000 as a bridge to heart transplantation underwent pump-off studies. Hemodynamics, vital signs and cognitive function were monitored; Doppler echocardiographic studies were done with the pump turned off for 5 minutes if tolerated. Regurgitant flow was assessed in terms of the difference between left ventricular and right ventricular outflow tract cardiac output (LVOT CO - RVOT CO). RESULTS: During pump-off periods, the mean regurgitant flow was 0.42 +/- 0.41 liter/min, and the mean arterial blood pressure was 63.1 +/- 11.6 mm Hg. There was no regurgitant flow when the pump was on. Three patients did not tolerate the pump being off for periods of 5 minutes; in these tests, the mean regurgitant flow rate was 0.54 +/- 0.50 liter/min, the mean arterial blood pressure was 52.8 +/- 9.8 mm Hg, and the mean pump-off time was 3.1 +/- 1.1 minutes. All patients remained conscious during the pump-off period, and none showed lasting adverse effects. CONCLUSIONS: Our findings suggest that patients being supported with the axial-flow Jarvik 2000 Heart LVAD can generally tolerate pump-off times of 5 minutes.

Adult↗
PubMed2006

Clinical experience with the TandemHeart percutaneous ventricular assist device.

The TandemHeart percutaneous ventricular assist device can be used to support patients in cardiogenic shock (until cardiac recovery occurs or as a bridge to definitive therapy) or as a temporary application during high-risk coronary interventions. The TandemHeart is a left atrial-to-femoral artery bypass system comprising a transseptal cannula, arterial cannulae, and a centrifugal blood pump. The pump can deliver flow rates up to 4.0 L/min at a maximum speed of 7500 rpm. From May 2003 through May 2005, the TandemHeart was used to support 18 patients (11 in cardiogenic shock and 7 undergoing high-risk percutaneous transluminal coronary angioplasty). The patients in cardiogenic shock were supported for a mean of 88.8 +/- 74.3 hours (range, 4-264 hr) at a mean pump flow rate of 2.87 +/- 0.56 L/min (range, 1.8-3.5 L/min). The mean cardiac index improved from 1.57 +/- 0.31 L/min/m2 before support to 2.60 +/- 0.34 L/min/m2 during support. The mean duration of support for the high-risk percutaneous transluminal coronary angioplasty patients was 5.5 +/- 8.3 hours (range, 1-24 hr). The mean flow rate was 2.42 +/- 0.55 L/min (range, 1.5-3.0 L/ min). The overall 30-day survival rate was 61%. In our experience, the TandemHeart device was easy to insert and provided a means either to cardiac recovery or to continued support with an implantable left ventricular assist device.

Aged↗
PubMed2006

Saphenous vein graft flow during left ventricular assistance with an axial-flow pump.

The effects of continuous-flow support on bypass graft flow have not been quantified clinically. Continuous-flow left ventricular assist devices unload the left ventricle throughout the cardiac cycle, which narrows pulse pressure and converts passive left ventricular filling during diastole to active flow throughout the cardiac cycle. We report the case of a 63-year-old man with severe congestive heart failure who underwent coronary artery bypass grafting and was supported with an axial-flow pump. In this patient, saphenous vein graft flow during left ventricular assistance provided adequate coronary perfusion.

Coronary Artery Bypass↗
PubMed2005

Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device.

The long-term effects of axial-flow mechanical circulatory support in humans are unclear. We report 3 cases of chronic gastrointestinal bleeding after implantation of a Jarvik 2000 axial-flow left ventricular assist device. The bleeding was refractory to aggressive management and in 2 cases resolved only after orthotopic cardiac transplantation.

Aged↗
PubMed2005

Direct thrombolytic therapy for intraventricular thrombosis in patients with the Jarvik 2000 left ventricular assist device.

One of the complications that can occur with continuous, axial-flow left ventricular assist devices (LVADs) is thrombosis within the left ventricle, adjacent to the device's inflow conduit, which may cause inflow obstruction and recurrent heart failure. We describe 2 cases in which we used a catheter to continuously infuse recombinant tissue plasminogen activator (tPA) into the left ventricle until signs of successful thrombolysis was achieved. By monitoring the result and administering only as much tPA as necessary to achieve thrombolysis, we were able to successfully lyse the obstructing thrombus with a minimal dose of tPA without causing any significant bleeding problems. This technique may be useful for managing this potentially serious complication while minimizing the risk of treatment.

Cardiac Catheterization↗
PubMed2005

Nitric oxide versus prostaglandin E1 for reduction of pulmonary hypertension in heart transplant candidates.

BACKGROUND: We sought to directly compare the effects of prostaglandin E1 (PGE1) and nitric oxide (NO) in testing for pulmonary hypertension reversibility in heart transplant candidates. METHODS: We included 19 heart transplant candidates who fulfilled at least 1 of 3 criteria: pulmonary vascular resistance (PVR) of >4 Wood units; transpulmonary gradient (TPG) of >12 mmHg; or systolic pulmonary artery pressure (PAP) of >60 mmHg. Patients randomly received either PGE1 (0.05, 0.2 and 0.5 microg/kg/min) or NO (40, 60 and 80 ppm) and were crossed-over to the second medication after receiving the maximal dose of the first. RESULTS: With PGE1, TPG decreased by 21% (baseline 20.3 +/- 6.8 mmHg; final 16.0 +/- 7.0 mmHg) compared to a 34% decrease with NO (baseline 20.8 +/- 6.2 mmHg; final 13.8 +/- 5.4 mmHg) (p = 0.13). PVR decreased by 42% with PGE1 (baseline 6.2 +/- 4.0 Wood units; final 3.6 +/- 1.8 Wood units) and by 47% with NO (baseline 6.0 +/- 3.9 Wood units; final 3.2 +/- 1.6 Wood units) (p = 0.87). Mean systemic pressure decreased with PGE1 (baseline 76.1 +/- 10.5 mmHg; final 69.4 +/- 12.2 mmHg; -9%) but not with NO administration (baseline 70.2 +/- 14.7 mmHg; final 71.6 +/- 10.9 mmHg; +2%) (p = 0.01). TPG was lowered to <12 mmHg in 14 patients. Of these, 6 (46%) responded to both PGE1 and NO, 4 (27%) responded only to PGE1, and 4 (27%) responded only to NO. CONCLUSIONS: The effects of PGE1 and NO on pulmonary hypertension are comparable, with PGE1 having more systemic hypotensive effects. Due to variability of patient responses, we recommend multiple rather than single-agent pharmacologic testing for the reversibility of pulmonary hypertension.

Administration, Inhalation↗
PubMed2005

Role of B-type natriuretic peptide and effect of nesiritide after total cardiac replacement with the AbioCor total artificial heart.

Endogenous B-type natriuretic peptide (BNP) is thought to be produced in the cardiac ventricles. After sub-total cardiectomy and implantation of a total artificial heart (TAH), the abrupt withdrawal of BNP impairs renal function despite normal hemodynamic variables. We hypothesized that abrupt withdrawal of endogenous BNP may impair renal function and volume homeostasis and BNP may have a direct renal influence unrelated to its cardiovascular effect. Nesiritide infusion should be supplemented in the interim and weaned slowly until BNP levels normalize, which suggests that BNP is produced in tissues other than the cardiac ventricles.

Acute Kidney Injury↗
PubMed2005

Thirty-five years of mechanical circulatory support at the Texas Heart Institute: an updated overview.

Since the 1960s, the Texas Heart Institute has been intimately involved in the development of mechanical circulatory support devices (for example, ventricular assist devices, aortic counterpulsation pumps, and total artificial hearts) for both short- and long-term use. Here, we review the varied clinical experience with these technologies at the Texas Heart Institute over the last 35 years.

Assisted Circulation↗
PubMed2005

Echocardiographic evaluation of the Jarvik 2000 axial-flow LVAD.

From April 2000 through September 2001, we studied 11 patients with the Jarvik 2000--a left ventricular assist device with an axial-flow pump that provides continuous blood flow--to determine the echocardiographic characteristics. All patients underwent complete echocardiographic examination, including outflow-graft flow evaluation 24 hours after implantation and each month thereafter for the duration of support. Data were obtained at each pump setting (8000-12000 rpm in 1000-rpm increments) and with the pump off. Left ventricular dimensions and shortening fraction and the duration of aortic valve systolic opening decreased as pump speed increased. Although the aortic valve remained closed at higher pump speeds, pump outflow-graft flow remained pulsatile, because of the systolic thrust of the assisted ventricle. Systolic dominance of phasic flow was more pronounced at lower pump speeds, due to normalization of the diseased heart's Starling response. When the aortic valve was closed continuously, echocardiographic contrast (indicating blood stasis) was noted in the aortic root. Because of the pump outflow graft's proximity to the chest wall, device output could be measured independently of cardiac contributions. Mean peak outflow-graft flow velocities were 0.75 +/- 0.30 m/s (systolic) and 0.41 +/- 0. 13 m/s (diastolic). When the pump was turned off briefly there was minimal regurgitation through the device into the left ventricle. This 1st echocardiographic heart function analysis of the Jarvik 2000 confirms that the device unloads the ventricle and increases cardiac output. Cardiac responses to device-speed changes can be evaluated readily with echocardiography in the early and late postoperative period.

Blood Flow Velocity↗
PubMed2005

The effect of LVAD aortic outflow-graft placement on hemodynamics and flow: Implantation technique and computer flow modeling.

Axial-flow ventricular assist devices (VADs) can be implanted either through a left thoracotomy with outflow-graft anastomosis to the descending thoracic aorta or through a midline sternotomy with anastomosis to the ascending aorta. Each method has advantages and disadvantages. Because these VADs produce nonpulsatile flow, their hemodynamic characteristics differ from those of pulsatile devices. These differences may have important clinical consequences, particularly in relation to the outflow-graft configuration. We describe a computer-generated flow model that we created to illustrate the flow dynamics and possible clinical consequences of each method. The simulations indicate that the location of the anastomosis has important qualitative effects on flow in the ascending aorta and aortic arch. At high VAD outputs (> or =75%), native cardiac output cannot supply the carotid and subclavian arteries. With a descending aortic anastomosis, net backward flow occurs in the descending aorta to supply these branches. Consequently, the aortic arch has a region with almost no net flow, where fluid particles stagnate over many cardiac cycles, possibly causing thrombogenesis. With an ascending aortic anastomosis, the arch has no stagnant region, although flow turbulence still occurs. When the aortic valve remains closed, so that the total output occurs through the VAD, the aortic root has a region of nearly stagnant flow. With an ascending aortic anastomosis, a small degree of recirculatory flow may prevent complete stagnation at the aortic root. With the descending aortic anastomosis, however, no recirculation occurs. These results help delineate the complex flow dynamics and the advantages and drawbacks of each technique.

Aortic Valve↗
PubMed2004

Clinical experience with an implantable, intracardiac, continuous flow circulatory support device: physiologic implications and their relationship to patient selection.

BACKGROUND: We have been investigating continuous-flow circulatory support devices for 20 years. Unlike pulsatile assist devices, continuous-flow pumps have a simplified pumping mechanism and they do not require compliance chambers or valves. In the 1980s, clinical experience with the Hemopump proved a high-speed, intravascular, continuous-flow pump could safely augment the circulation. Subsequently, a decade of animal experiments with a larger, longer-term continuous-flow pump (the Jarvik 2000) confirmed the safety and efficacy of intraventricular placement, leading to its clinical application. METHODS: We analyzed the physiologic and anatomic effect of using the Jarvik 2000 pump for cardiac support in 23 patients in whom the device was applied as a bridge to transplant under the protocol approved by the Food and Drug Administration Investigational Device Exemption. The device was used as a bridge to transplantation in 20 patients and as destination therapy in 3 patients. RESULTS: In the bridge-to-transplant group, 14 patients underwent transplantation, 5 died during the circulatory support period and 1 is in an ongoing study. The support period lasted an average of 90 days. For the survivors, the follow-up period has averaged 16 months. Within the first 48 postoperative hours, the average cardiac index increased by 65% (from 1.77 +/- 0.24 to 2.92 +/- 0.60 L. min(-1). m(-2), p = 0.00000002), the systemic vascular resistance decreased by 42% (from 1604 +/- 427 to 930 +/- 330 dynes/sec per cm(2), p = 0.00001), and the pulmonary capillary wedge pressure (PCWP) decreased by 41.8% (from 23 +/- 5.1 to 13.4 +/- 6.6 mm Hg, p = 0.00009). Similar results were seen for the patients undergoing destination therapy. Cardiac index increased 89.5% (from 1.9 +/- 0.1 to 3.6 +/- 0.6, p = 0.046) and PCWP decreased by 52.2% (from 23 +/- 10 to 11 +/- 2, p = 0.22). In that group, 1 patient died unexpectedly from an accident 382 days after device implantation. The 2 survivors remain in New York Heart Association (NYHA) functional class I at 700 to 952 days after implantation. CONCLUSIONS: The Jarvik 2000 can offer effective long-term support for patients with chronic heart failure and NYHA class IV status. However, the new physiology produced by continuous offloading of the heart throughout the cardiac cycle has introduced unique clinical problems. The understanding of the problems generated by this biotechnological interface is essential for obtaining optimal clinical outcomes.

Adult↗
PubMed2004

Use of the Flowmaker (Jarvik 2000) left ventricular assist device for destination therapy and bridging to transplantation.

The Flowmaker left ventricular assist device (formerly known as the Jarvik 2000) is an axial-flow pump that provides continuous flow from the left ventricle to the aorta. Designed for either temporary or permanent use, the Flowmaker is undergoing clinical trials in the United States and Europe. The goal of this therapy is to provide adequate circulatory flow while partially reducing the left ventricular size and end-diastolic pressure. This gives the native ventricle an opportunity to remodel itself. Those who benefit the most from this technology are patients who require only true left ventricular assistance rather than total capture of the left ventricular output. Because of the Flowmaker's simplicity and safety of implantation, as well as the absence of late pump failure, its use may be justified in severely impaired class III and IV (but not preterminal) heart failure patients.

Clinical Trials as Topic↗
PubMed2004

Hemodynamic support with a percutaneous left ventricular assist device during stenting of an unprotected left main coronary artery.

Coronary artery bypass grafting prolongs survival in patients with left main coronary artery stenosis. However, this benefit is denied to patients who refuse the procedure or who are poor surgical candidates due to comorbid conditions. We describe a novel technique for the percutaneous revascularization of stenosis in an unprotected left main coronary artery in high-risk patients. The TandemHeart, a percutaneously inserted left ventricular assist device, was used to provide periprocedural hemodynamic support during angioplasty and stenting of an unprotected left main coronary artery for stenosis in a 70-year-old woman. The device was removed immediately after the procedure, and the patient was discharged from the hospital on the 2nd postprocedural day. The potential advantages of angioplasty with the support of percutaneous left ventricular assist devices in high-risk patients are discussed.

Aged↗