Initial clinical experience with the Jarvik 2000 implantable axial-flow left ventricular assist system

BACKGROUND: Implantable left ventricular assist systems (LVASs) are used for bridging to transplantation, bridging to myocardial improvement, and for permanent circulatory support. Conventional implantable systems have inherent limitations that increase morbidity during support. In contrast, small, efficient, axial-flow pumps, which have been under development for the past decade, have the potential to improve the length and quality of life in patients with severe heart failure. Methods and Results- To assess the safety and clinical utility of the Jarvik 2000, we implanted this device in 10 transplant candidates (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation was achieved through a left thoracotomy during partial cardiopulmonary bypass. The mean support period was 84 days. Within 48 hours postoperatively, the cardiac index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Eight patients underwent physical rehabilitation and returned to NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and pressure-volume loop analyses showed good left ventricular unloading. Seven patients underwent transplantation and 3 died during support. No device thrombosis was observed at explantation. CONCLUSIONS: The Jarvik 2000 functions as a true assist device by partially unloading the left ventricle, thereby optimizing the patient's hemodynamics. Our preliminary results indicate that this LVAS may safely provide circulatory assistance for heart transplant candidates.     

Effect of single lung transplantation on pulmonary hypertension in patients with end stage fibrosing lung disease.

OBJECTIVE--To investigate the effect of successful single lung transplantation on pulmonary haemodynamic variables and right ventricular function. DESIGN--Pulmonary haemodynamic variables and right ventricular function were measured at right heart catheterisation after single lung transplantation. The results were compared with the preoperative pulmonary haemodynamic variables measured at the time of assessment for transplantation. SETTING--A tertiary referral centre. PATIENTS--Five survivors of single lung transplantation performed for end stage lung disease. INTERVENTIONS--Cardiac catheterisation in all five patients at a mean of 18 months postoperatively. Preoperative catheter data were available for comparison in four. Right heart pressures and cardiac output were measured and right ventricular angiography was performed. Perfusion scans performed for clinical reasons were used to assess the percentage of cardiac output passing through each lung. MAIN OUTCOME MEASURES--Right heart pressures, cardiac output, right ventricular function, percentage perfusion to lungs. RESULTS--After operation mean peak right ventricular pressure fell from 53 mm Hg to 33 mm Hg, mean pulmonary artery pressure from 33 mm Hg to 18 mm Hg, total pulmonary resistance from 11.2 U x m2 to 5.8 U x m2, and pulmonary arteriolar resistance from 8.9 U x m2 to 3.6 U x m2. Pulmonary artery wedge pressure and cardiac index were unchanged. Right ventricular function improved in all patients. The transplanted lung received most of the cardiac output. CONCLUSION--In patients with moderate pulmonary hypertension and right ventricular dysfunction secondary to end stage fibrosing lung disease single lung transplantation was followed by an improvement in pulmonary haemodynamic variables and right ventricular function.     

Effect of single lung transplantation on pulmonary hypertension in patients with end stage fibrosing lung disease.

OBJECTIVE--To investigate the effect of successful single lung transplantation on pulmonary haemodynamic variables and right ventricular function. DESIGN--Pulmonary haemodynamic variables and right ventricular function were measured at right heart catheterisation after single lung transplantation. The results were compared with the preoperative pulmonary haemodynamic variables measured at the time of assessment for transplantation. SETTING--A tertiary referral centre. PATIENTS--Five survivors of single lung transplantation performed for end stage lung disease. INTERVENTIONS--Cardiac catheterisation in all five patients at a mean of 18 months postoperatively. Preoperative catheter data were available for comparison in four. Right heart pressures and cardiac output were measured and right ventricular angiography was performed. Perfusion scans performed for clinical reasons were used to assess the percentage of cardiac output passing through each lung. MAIN OUTCOME MEASURES--Right heart pressures, cardiac output, right ventricular function, percentage perfusion to lungs. RESULTS--After operation mean peak right ventricular pressure fell from 53 mm Hg to 33 mm Hg, mean pulmonary artery pressure from 33 mm Hg to 18 mm Hg, total pulmonary resistance from 11.2 U x m2 to 5.8 U x m2, and pulmonary arteriolar resistance from 8.9 U x m2 to 3.6 U x m2. Pulmonary artery wedge pressure and cardiac index were unchanged. Right ventricular function improved in all patients. The transplanted lung received most of the cardiac output. CONCLUSION--In patients with moderate pulmonary hypertension and right ventricular dysfunction secondary to end stage fibrosing lung disease single lung transplantation was followed by an improvement in pulmonary haemodynamic variables and right ventricular function.     

The haemodynamic effects of amrinone in patients with mitral stenosis and pulmonary hypertension

The aim of this study was to investigate the haemodynamic effects of amrinone in patients with pulmonary hypertension and impaired right ventricular function. Twelve patients with mitral stenosis (NYHA classification III and IV) took part in the study. The haemodynamic measurements were performed in the steady state under anaesthesia prior to surgery. The patients received a bolus injection of 1.5 mg kg-1 amrinone; haemodynamic measurements were taken at 3, 5, 10, 15, 20 and 30 min. Amrinone increased cardiac index by approximately 30%, heart rate rose from on average 76 to 82 beats per minute. Whereas pulmonary capillary pressure did not change significantly, mean pulmonary artery pressure fell clearly from 33 to 28 mmHg. A decrease in the elevated pulmonary vascular resistance of about 40% was calculated. The higher the initial value for resistance in the pulmonary circulatory system, the more marked was the reduction (r = 0.96). The study shows that amrinone induces a vasodilation in the pulmonary circulatory system. A reduction in ventricular afterload is of great significance particularly for the therapy of right heart insufficiency. Amrinone therefore appears to be a suitable substance with its observed vasodilating and its well known positive inotropic effects for the treatment of right heart failure in cases of pulmonary hypertension.     

Successful cardiac transplantation after 38 days of circulatory assistance with a heterotopic artificial heart

The survival of a patient with irreversible cardiac failure on the cardiac transplantation waiting list was assured for 38 days by circulatory assistance with heterotopic Pierce Donachy prosthetic ventricles and followed by successful cardiac transplantation. This method of circulatory assistance is relatively simple to install from the technical point of view and provides a satisfactory haemodynamic result whilst waiting for a compatible donor organ. Several complications, some of them serious, were observed. Some were related to the patient's poor preoperative condition: acute renal failure, disorders of coagulation. These regressed slowly when the patient's haemodynamic status improved. On the other hand, septic problems and local haemorrhage were inherent to this technique. These are the commonest complications reported by other authors. Although the mortality rate during the period of circulatory assistance may appear to be high, this technique remains a valuable method of survival for selected patients and does not affect the chances of success of ulterior cardiac transplantation.     

Management of acute severe perioperative failure of cardiac allografts: a single-centre experience with a review of the literature

BACKGROUND: Early graft failure is associated with high mortality and is the main cause of death within the first 30 days after transplantation. The purpose of the present study was to examine the investigators' experience of severe perioperative acute graft failure and to review the literature. METHODS: Nine of 385 cardiac transplants (2.3%) performed from 1984 through 2005 developed severe perioperative acute graft failure either in the operating room or within 24 h after cardiac transplantation. Four patients had primary graft failure, two had right heart failure secondary to pulmonary hypertension, one had hyperacute rejection, one had accelerated acute rejection and one possibly sustained a particulate coronary embolus intraoperatively. RESULTS: All except the two patients who had right heart failure secondary to pulmonary hypertension received mechanical circulatory support. Three patients were supported with total artificial hearts, two patients received a left ventricular assist device, one patient was supported with extracorporeal life support followed by a right ventricular assist device when the left ventricle recovered, and one patient was supported for several hours with cardiopulmonary bypass. Three patients were retransplanted after mechanical circulatory support, but only one survived. Only one of the nine patients (11%) survived; this patient was supported with a total artificial heart followed by retransplantation. CONCLUSION: The outcome of severe perioperative acute graft failure is very poor. Mechanical circulatory support and retransplantation are not as successful as in other situations. Due to the shortage of donors and poor outcomes, retransplantation for hyperacute rejection is not advisable.     

Acute circulatory effects of dopamine in patients with pulmonary hypertension.

Twenty-one patients, 11 with normal pulomonary artery pressures and 10 with pulmonary hypertension, had haemodynamic measurements performed before and during dopamine infusion while undergoing cardiac catheterization, in order to evaluate the circulatory effects of dopamine in pulmonary hypertension. In both groups on average, heart rate, pulmonary artery mean pressure, aortic mean pressure, and cardiac index increased significantly, while systemic vascular resistance fell significantly during dopamine administration. In neither group did the average pulmonary vascular resistance or right ventricular end-diastolic pressure change significantly. We conclude that dopamine is a safe and potentially useful drug for the treatment of reduced cardiac output, even in patients with pulmonary hypertension.     

Acute circulatory effects of dopamine in patients with pulmonary hypertension.

Twenty-one patients, 11 with normal pulomonary artery pressures and 10 with pulmonary hypertension, had haemodynamic measurements performed before and during dopamine infusion while undergoing cardiac catheterization, in order to evaluate the circulatory effects of dopamine in pulmonary hypertension. In both groups on average, heart rate, pulmonary artery mean pressure, aortic mean pressure, and cardiac index increased significantly, while systemic vascular resistance fell significantly during dopamine administration. In neither group did the average pulmonary vascular resistance or right ventricular end-diastolic pressure change significantly. We conclude that dopamine is a safe and potentially useful drug for the treatment of reduced cardiac output, even in patients with pulmonary hypertension.     

Asynchronous ventricular relaxation

The clinical effects of early application of external pressure circulatory assistance (EPCA) in acute myocardial infarction were evaluated in a prospective, randomized trial involving 258 patients in 25 institutions. All patients had mild left ventricular failure and received circulatory assistance within the first 24 hours after the onset of symptoms. There were no significant differences between the treatment and control groups, consisting of 142 patients and 116 patients, respectively, with regard to age, sex, race, previous cardiac history, electrocardiographic location of myocardial infarction, Norris prognostic index, admission heart rate, blood pressure and chest roentgenogram, and time from onset of symptoms to hospital admission. There were also no differences between the treatment and control groups with regard to antiarrhythmic, positive inotropic, diuretic and vasodilator therapy. Hospital mortality was significantly decreased, compared with that of control patients, in the group receiving 4 or more hours of external pressure circulatory assistance within the first 24 hours after admission (mortality rate 6.5 percent [7 of 108] in treatment group versus 14.7 percent [17 of 116] in control group, p < 0.05). Circulatory assistance for 3 or more hours was also associated with a lower mortality rate in the subgroup (patients 46 or more years old) to which mortality in this study was confined (mortality rate 8.3 percent [9 of 109] in the treatment group versus 17.5 percent [17 of 97] in the control group, p < 0.05). For the combined group of patients with 3 or more and 4 or more hours of treatment, circulatory assistance was associated with significant lessening (p < 0.05 to < 0.01) of morbidity as manifested by recurrent chest pain, progression of cardiac failure, occurrence of ventricular fibrillation, change in heart size and clinical cardiac functional status at discharge. These data support further application and investigation of external pressure circulatory assistance in myocardial infarction.     

Myocardial infarction caused by the thrombosis of the common trunk of the left coronary artery. Fatal outcome despite an early obstruction removal by angioplasty. Apropos of a case

We report an exceptional case of acute myocardial infarction due to thrombosis of the left main coronary artery in a 39-year old male patient. After failure of recanalization by systemic fibrinolysis, percutaneous angioplasty under circulatory assistance was successfully performed pending a possible transplantation. The patient unfortunately died of haemodynamic disturbances 48 hours after the infarction.     

Comparison of the effects of phentolamine and trinitrine in the treatment of left ventricular failure during the acute phase of myocardial infarct]

Two groups of 10 patients with left ventricular failure during the acute phase of myocardial infarction were studied. One group were given phentolamine, the other trinitrin. The infusion rate was regulated so that the heart rate was not increased by more than 10 beats per minute, and to obtain a pulmonary arterial diastolic pressure less than 18 mmHg with a mean systemic arterial pressure remaining greater than or equal to 80 mmHg. The dose of phentolamine was 5 +/- 3 mcg/kg/mn, but using trinitrin the initial optimal dose of 0.39 +/- 0.22 mcg/kg/mn had to be progressively increased during the first 24 hours. The haemodynamic study done before treatment and after an hour at the optimal infusion rate showed that, for a similar reduction in the pulmonary arterial diastolic pressure, the mean systemic arterial pressure was reduced less by trinitrin than by phentolamine, while the stroke work index was not appreciably altered by either drug. In patients with low systemic arterial pressure, trinitrin appears to be preferable and warrants use after the possible setting up of circulatory assistance by aortic counter-pulsation.     

Towards a non-invasive left-ventricular assisted circulation. Experimental study

An original system of closed chest direct left ventricular circulatory assistance was assessed in the dog. The system comprises a compact centrifugal pump, a left ventricular cannula for aspiration and an arterial cannula for reinjection of the blood. The cannulae may be introduced by retrograde arterial catheterisation, the first by retrograde transaortic catheterisation and the second positioned in the descending thoracic aorta. This circuit was evaluated in a dog model of acute myocardial infarction involving 39+/-8 p. 100 of left ventricular mass. Mechanical circulatory assistance maintained an extracorporeal output (78+/-5 ml/min/kg) identical to the cardiac output measured immediately beforehand. Left ventricular emptying was complete (LVEDP = -2.3+/-2.5 torr), its external work becoming nil. The pulmonary artery pressure (13.1+/-0.8 torr) and pulmonary artery resistances (311+/-28 dynes/cm.s-5) were significantly lower, whilst no increase in systemic resistance was observed (3 134+/-300 dynes/cm.s-5). During the new haemodynamic equilibrium St segment elevation at the centre and at the edge of the cyanosed myocardium was significantly reduced to (p < 0.05). Irreduceable ventricular fibrillation at coronary artery ligature occurred in two animals. Spontaneous reversion to sinus rhythm was observed when circulatory assistance was started. Termination of left ventricular circulatory assistance after 2 hours was accompanied by a significant (p < 0.005) fall in cardiac index (59+/-7 ml/min/kg), increase in left ventricular filling pressure (LVEDP 7.8+/-1.8 torr), increase in systemic resistance (3 803+/-404 dynes/cm.s-5). The electrical changes of myocardial ischemia worsened (p < 0.005). No valvular or parietal complications of cannulization were observed. This protocol shows the practical value of the original left ventricular circulatory assistance circuit described. The results suggest that a significant reduction of myocardial ischemia due to coronary artery ligature may be achieved by this means. a clinical trial of the value of this extra corporeal circulatory assistance in the treatment of cardiogenic shock is suggested.     

Resolution of severe pulmonary hypertension after heterotopic cardiac transplantation

In patients with severe congestive heart failure, a marked elevation in pulmonary vascular resistance limits the success of orthotopic cardiac transplantation, thus providing the rationale for heterotopic transplantation. To determine the changes in pulmonary hemodynamics after heterotopic cardiac transplantation, postoperative right heart pressures were serially measured in five patients who underwent this operation for end-stage congestive heart failure accompanied by severe secondary pulmonary hypertension and elevation in calculated pulmonary vascular resistance. Hemodynamics were compared with those of a matched group of 10 orthotopic cardiac transplant recipients. Preoperatively, pulmonary artery mean and wedge pressures, pulmonary vascular resistance and transpulmonary pressure gradient (pulmonary artery mean minus wedge pressure) were significantly higher in the heterotopic group. Postoperatively, significant improvement in pulmonary hemodynamics occurred in both groups and, by 12 months, the pulmonary artery mean pressure, wedge pressure, pulmonary vascular resistance and transpulmonary pressure gradient were similar in the two groups. These findings suggest that pulmonary hypertension secondary to congestive heart failure, even when severe and associated with a high pulmonary vascular resistance, is to a great extent reversible.     

Sulmazole: a new positive inotropic agent

Sulmazol (AR-L 115 BS) is a new positive inotropic agent with arterial and venous vasodilator properties. The authors studied the effects of a 24 hours intravenous infusion (an injection of 0.5 mg/kg over 1 minute, followed by an infusion of 1.4 mg/min) on the major haemodynamic parameters of 17 patients with heart failure: 10 patients with chronic decompensation (group I) and 7 patients with heart failure as a result of acute myocardial infraction (group II). The haemodynamic criteria of inclusion were a cardiac index less than or equal to 2.5 l/min/m2 and a pulmonary capillary pressure greater than or equal to 18 mm Hg. After 6 hr of the infusion, the cardiac index increased in both groups (45%, p less than 0.001 and 40%, p less than 0.001 respectively); the pulmonary capillary pressure decreased (32%, p less than 0.001 and 30%, p less than 0.001) and the right atrial pressure decreased (51%, p less than 0.005 and 31%, NS). The total systemic resistance was also decreased (32%, p less than 0.001 and 34%, p less than 0.001), but there was no significant change in the systolic blood pressure. The heart rate increased only in group II (17%, p less than 0.001). These beneficial hemodynamic effects lasted for the 24 hours of the infusion. Sulmazol was therefore found to be very effective in the treatment of acute and chronic heart failure; its long term tolerance still needs to be demonstrated.     

Quality of life in bridge-to-transplant patients with chronic heart failure after implantation of an axial flow ventricular assist device

Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation.     

Dose-response relation of intravenous enoximone in congestive cardiac insufficiency

Enoximone (MDL 17043) is a new generation inotropic drug which acts by inhibiting phosphodiesterase and is endowed with both inotropic and vasodilator properties. The purpose of this study, which involved 23 patients aged from 18 to 75 years in NYHA class III or IV and with evidence of severe haemodynamic disturbances (cardiac index below 2.5 1/mn/m2, pulmonary wedge pressure above 15 mmHg), was to evaluate the acute haemodynamic responses to doses of enoximone that ranged from 0.25 to 2.50 mg/kg administered by bolus intravenous injection. Heart failure was either of ischaemic origin (6 cases) or idiopathic (10 cases) or due to various causes (7 cases). Group A patients (n = 11) received the drug in low doses (less than or equal to 1 mg/kg) as opposed to group B patients (n = 12) who were given high doses (greater than 1 mg/kg). Results were evaluated from the amplitude and duration of the haemodynamic response at maximum effect time (30 min). The following parameters were measured: cardiac index, pulmonary wedge pressure, systemic vascular resistance, mean arterial pressure and heart rate. Cardiac index and pulmonary wedge pressure were significantly improved in both groups (P less than 0.005): cardiac index +39 p. 100 in group A, +55 p. 100 in group B; pulmonary wedge pressure -36 p. 100 in group A, -48 p. 100 in group B; systemic vascular resistance -46 p. 100 in group B. Heart rate and arterial pressure were not significantly altered. The duration of response was 1 to 3 hours in group A patients and 4 to 8 hours in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic effects of metoprolol and intravenous nitroglycerin versus metoprolol alone in patients with acute myocardial infarction

Among the various treatments adopted to protect the acutely ischaemic myocardium, favourable results have been reported for beta-blockers. Nitrates can also reasonably be expected to exert favourable effects in acute myocardial infarction considering their haemodynamic action. In this study we compared the haemodynamic effect of metoprolol alone with the effect of metoprolol plus nitroglycerin. Fourteen patients, admitted within 12 hours from the clinical onset of acute myocardial infarction, were initially given intravenous metoprolol (5 + 5 + 5 mg) followed 15 minutes later by an additional 50 mg oral dose. Thereafter, they were randomly allocated to a treatment with metoprolol alone (Group 1) or metoprolol plus intravenous nitroglycerin (Group 2). The two groups were comparable with regard to age, sex, time to admission, time to therapy, site of necrosis, Killip class, and infarct size. Acute beta-blockade induced a marked decrease of cardiac output, systolic blood pressure and heart rate along with a small increase of pulmonary wedge pressure and a marked systemic vasoconstriction. In Group 1 patients these haemodynamic changes persisted up to twelve hours after randomization; in Group 2 patients the addition of nitroglycerin induced a prompt decrease of pulmonary wedge pressure and peripheral vascular resistance whereas the double product was unchanged. In conclusion, intravenous nitroglycerin induces a beneficial haemodynamic effect after early beta-blockade with metoprolol.     

Haemodynamic dose-response effects of intravenous beta-blocking drugs with different ancillary properties in patients with coronary heart disease

The haemodynamic dose-response effects of propranolol, practolol,oxprenolol and metoprolol were compared in a randomized single-blindstudy in 24 patients with stable coronary heart disease. Thedoses of drugs used gave approximately equal degrees of inhibitionof exercise tachycardia. The haemodynamic profile in the controlperiod was stable and similar in each group. All four drugs consistently reduced heart rate and cardiac outputand increased pulmonary wedge pressure, but the changes weresignificantly greater after propranolol and metoprolol thanafter practolol and oxprenolol. There was no significant differencebetween the effects of the four drugs on calculated stroke volume.The increase in the calculated systemic vascular resistancewas similar after all four drugs. These observations indicate that when administered intravenouslyto patients with coronary heart disease in equivalent negativechronotropic doses, drugs with intrinsic sympathomimetic activity(e.g. practolol and oxprenolol) resulted in less depressionof left ventricular pumping function than drugs without thisproperty. The possession of cardioselectivity (e.g. practololand metoprolol) did not appear to confer any haemodynamic benefit.     

Assisted circulation by external heterotopic prosthesis as a bridge to heart transplantation

Eleven patients aged 7 to 58 years were placed on assisted circulation with Pierce (2 cases) or Abiomed (9 cases) external prosthetic ventricles as a bridge to cardiac transplantation. The indications were terminal cardiac failure following cardiomyopathy (7 cases), decompensated ischemic heart disease (3 cases) and subacute post-transplantation rejection (1 case). The duration of the assisted circulation ranged from 24 hours to 11 days. All patients were transplanted but 3 died after transplantation (27%). The circulatory assistance was satisfactory in all patients as shown by the regression of clinical signs of low cardiac output and the normalisation of diuresis. The complications observed during assisted circulation and after cardiac transplantation were: haemorrhage (36%), infection (27%) and thromboembolism (9%). These preliminary results with a 72% post-transplantation survival rate, show that both systems are effective "bridges to cardiac transplantation". The Abiomen device is excellent value for money and relatively simple to install and represents a good compromise between the sophisticated techniques of circulatory assistance and the problems of the cost of health care.     

Prognostic and therapeutic considerations in clinical primary pulmonary hypertension

Twenty-two patients with primary pulmonary hypertension were reviewed to assess the correlation of clinical and haemodynamic features with prognosis. A relationship between resting haemodynamic measurements and survival was sought in all 22 patients, and the effect of vasodilator therapy in 13 was reviewed. Those who survived 12 months or less (seven patients) or 40 months or more (seven patients) from catheterization were classified into short or long survival groups respectively. Clinical, haemodynamic and pulmonary angiographic features of patients in these groups were compared. In the whole group, mean pulmonary artery pressure and pulmonary vascular resistance were inversely related to survival. Multivariate analysis of mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), mean right atrial pressure (RAP), systemic vascular resistance (SVR) and cardiac index (CI) in the whole group identified RAP and PVR as the model which best predicted survival time. The short survival group had a higher prevalence of electrocardiographic evidence of right ventricular hypertrophy, higher mean pulmonary artery pressure and pulmonary vascular resistance than the long survival group. Our experience with vasodilator therapy was less encouraging than that described by other workers. Two of six patients on long-term treatment appeared to stabilize. Two other untreated patients showed spontaneous improvement. Prediction of prognosis in the individual patient is difficult.