Pedro Catarino

First permanent implant of the Jarvik 2000 Heart

BACKGROUNDnHeart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure.nnnMETHODSnAs part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure.nnnFINDINGSnThe Jarvik 2000 Heart sustained the patients circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well.nnnCONCLUSIONSnThe initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

End-organ function during chronic nonpulsatile circulation

BACKGROUNDnEvolving blood pump technology has produced user-friendly continuous flow left ventricular assist devices, but uncertainty exists about the safety of chronic nonpulsatile circulation. We established consistently nonpulsatile blood flow in a sheep model using the Terumo magnetically suspended centrifugal pump. We then compared end-organ function between pulseless and control animals.nnnMETHODSnFifteen healthy sheep (65 to 85 kg) were allocated to either left ventricular assist device (n = 9) or control (n = 6) groups. We implanted the device through a left thoracotomy and determined the flow rate at which pulse pressure was absent. The flow rate was then adjusted to exceed that rate (4.2 +/- 1.5 L/min), and all variables of pump function were continuously monitored by computer. Blood tests were taken serially for hepatic and renal function and plasma renin levels. The sheep were sacrificed electively at 30 (n = 3), 90 (n = 4), 180 (n = 1), and 340 (n = 1) days. Detailed histologic examination was made of the brain, liver, kidney, myocardium, and major arteries.nnnRESULTSnAll animals remained in good condition until sacrifice. All measures of end-organ function remained within normal limits for both groups. There were no histologic differences between the organs of pulsatile and nonpulsatile animals. Although there was no significant difference in mean blood pressure, plasma renin levels were substantially elevated in pulseless animals (1.4 +/- 0.3 pg/mL versus 2.9 +/- 0.3 pg/mL; p < 0.05). We also identified thinning of the medial layer of the ascending aorta in nonpulsatile sheep (1.8 +/- 0.4 mm in left ventricular assist device animals versus 2.6 +/- 0.6 mm in control sheep; p < 0.05).nnnCONCLUSIONSnChronic nonpulsatile circulation was well tolerated, and we found neither functional nor histologic changes in major end organs. The renin-angiotensin system was upregulated, but this did not provide a significant rise in blood pressure. The changes in the aortic wall merit further investigation. As a result of these findings, we consider that nonpulsatile devices can be used safely for long-term circulatory support.

Circulatory Support for Long-Term Treatment of Heart Failure Experience With an Intraventricular Continuous Flow Pump

Background—A lifetime mechanical solution for advanced heart failure must be reliable, with a low risk of life-threatening complications. After extensive laboratory testing, we began clinical trials with an axial flow pump for long-term treatment of New York Heart Association class IV, transplant-ineligible patients. Methods and Results—The Jarvik 2000 is a continuous flow device that is implanted in the apex of the left ventricle with offloading to the descending thoracic aorta. Skull-based percutaneous power delivery was derived from cochlear implant technology. We used this system in 4 patients with end-stage dilated cardiomyopathy. Exercise capacity, quality of life, device parameters, and native heart function were monitored serially. One patient died from right heart failure at 3 months. The other patients were discharged from hospital between 3 and 8 weeks postoperatively and are currently New York Heart Association I or II. Follow-up lasted between 9 and 20 months. There has been no device failure or hemolysis. Native heart function and quality of life were markedly improved. Conclusions—The Jarvik 2000 is a true assist (rather than replacement) device that functions synergistically with the native left ventricle and provides excellent quality of life. Adverse events are infrequent. This blood pump may provide a mechanical solution for end-stage heart failure in the community.

High-pressure suction drainage via a polyurethane foam in the management of poststernotomy mediastinitis

BACKGROUNDnThis study was performed to evaluate the effectiveness of suction drainage in the management of early poststernotomy mediastinitis.nnnMETHODSnFrom September 1998 to August 1999, we encountered nine cases of poststernotomy mediastinitis out of 1,209 adult median sternotomies performed in this time period. All these cases were treated with suction drainage, which was recently introduced to our management protocol. From September 1997 to August 1998, we encountered 11 cases of poststernotomy mediastinitis of 1,343 adult median sternotomies. All these cases were initially treated by closed drainage and irrigation, which was our previous first-line management. We used the latter group as historical controls for the evaluation of suction drainage. Lengths of hospitalization were compared using the Mann-Whitney U test, and success versus failure of the primary treatment was compared using the chi2 test.nnnRESULTSnTreatment with the suction dressing resulted in a decreased length of hospitalization after treatment starts (p = 0.02) and a lower rate of treatment failure (p = 0.03).nnnCONCLUSIONSnThe use of high-pressure suction drainage is a valuable adjunct in the early management of poststernotomy mediastinitis.

Reliable long-term non-pulsatile circulatory support without anticoagulation

OBJECTIVEnThe Terumo implantable left ventricular assist system (T-ILVAS) consists of a titanium centrifugal pump with a unique magnetically suspended impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior surface is heparin-coated and there is no purge system. We implanted the device into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability and biocompatibility.nnnMETHODSnThe T-ILVAS was implanted via left thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the left ventricular apex and a Dacron outflow graft anastomosed to the descending aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was given after the surgery. Suspension position, motor current, impeller speed and pump flow were continuously monitored and stored by on-line computer. Serial blood samples were collected to determine haematological and biochemical indices of renal function, liver function and haemolysis. All animals were electively euthanized between 3 and 7 months postoperatively. The explanted pumps were examined for mechanical reliability and thrombus formation. Major organs were examined macroscopically and histologically for thromboembolism.nnnRESULTSnAll animals appeared completely normal for up to 210 days. At speeds between 1500 and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There were no major complications (pump failure, thromboembolism, haemorrhage, or driveline infection). Indices of haemolysis, liver and renal function remained within normal limits. All pumps were mechanically sound and free from thrombus. One embolus was found in a sectioned kidney.nnnCONCLUSIONnThe T-ILVAS successfully supported the systemic circulation without anticoagulation for up to 210 days. Mechanical reliability and biocompatibility were demonstrated. Organ function remained within normal limits during continuous non-pulsatile flow.

Effects of Left Ventricular Volume Overload on Mitochondrial and Death-Receptor–Mediated Apoptotic Pathways in the Transition to Heart Failure

Cardiomyocyte apoptosis has been implicated in the pathogenesis of heart failure (HF). This study was performed in patients with left ventricular (LV) volume overload at different stages in the development of HF to correlate apoptotic gene expression with LV echocardiographic phenotype. LV biopsies were procured from 24 cardiac surgical patients selected from 4 distinct clinical groups (n = 6) in the progression from preserved LV function to HF. Group I consisted of control patients with normal LV function (e.g., with atrial myxoma), group II had aortic regurgitation with LV hypertrophy and preserved systolic function (ejection fraction >50%), group III had aortic regurgitation with LV dysfunction (ejection fraction 30% to 40%), and group IV had end-stage HF (ejection fraction <20%). Biopsies were used to measure mRNA expression of the genetic regulators of mitochondrial (Bad, Bax, Bcl-2, Bcl-xL, and p53) and death-receptor- (Fas and tumor necrosis factor receptor 1 [TNFR1]) mediated apoptotic pathways by reverse transcription-polymerase chain reaction. Caspase activity was determined using specific fluorogenic peptide substrates and immunohistochemistry. Evidence for apoptosis was obtained using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and in situ oligo ligation assays. Expression of proapoptotic factors (Bax, p53, TNFR1), antiapoptotic mitochondrial factor (Bcl-xL), and caspases 3, 8, and 9 increased progressively during the transition from preserved LV function to HF (p <0.05, analysis of variance). No significant difference was found for Bad, Bcl-2, or Fas. No evidence of DNA fragmentation was identified. In conclusion, activation of the cardiomyocyte apoptotic cascade occurs during the development of volume overload-induced HF. Mitochondrial (Bax, p53, caspase 9) and death-receptor mediated (TNFR1, caspase 8) pathways are upregulated but without completion of DNA fragmentation.

The Jarvik 2000 Heart. Clinical validation of the intraventricular position

OBJECTIVEnHeart failure is now a public health epidemic. Donor hearts are severely restricted in availability. Permanent mechanical circulatory support or bridge to myocardial recovery are emerging alternatives. After extensive laboratory experience we sought to evaluate the intraventricular Jarvik 2000 Heart in patients with endstage heart failure.nnnMETHODSnThe Jarvik 2000 Heart is a novel thumb-sized left ventricular assist device (LVAD) which is fitted within the apex of the native left ventricle. A vascular graft off loads this to the descending thoracic aorta. The pump rotor spins at between 8000 and 12,000 rpm providing 5-6 litres blood flow per minute. We have used the device with skull-mounted power delivery for seven permanent implants and trans-abdominal drive line for ten bridge-to-transplant patients.nnnRESULTSnAll patients survived the operation. Three died from non-device related complications. Survivors had early resolution of heart failure with return to NYHA I/II. All had pulsatile circulation. The device was user-friendly and imperceptible to the patient. Both the pump and native left ventricle contributed to the cardiac output during exercise. Seven patients have been transplanted successfully. All explanted devices were free from thrombus formation. Two permanent implant patients left hospital as early as 3 weeks postoperatively.nnnCONCLUSIONSnThe Jarvik 2000 is an effective user-friendly LVAD which allows early discharge from hospital. The intraventricular position has distinct advantages especially through absence of an inflow cannula. Synergy develops between the LVAD and native left ventricle. Early experience suggests that this may be a realistic LVAD to treat heart failure routinely in the outpatient setting.

A pressure overload model to track the molecular biology of heart failure

OBJECTIVESnPressure overload plays an important role in left ventricular remodelling and the development of heart failure. The underlying molecular mechanisms behind these processes are poorly understood at the myocyte level. To investigate this, we developed an ovine model of pressure overload-induced heart failure, in which serial left ventricular biopsies were obtained.nnnMETHODSnAdult male sheep were chronically banded with a novel variable aortic constriction device. This was progressively inflated via a subcutaneous port to increase left ventricular afterload. The animals were monitored clinically and echocardiographically. Serial left ventricular endomyocardial biopsies were obtained via the right external carotid artery under fluoroscopic guidance. They were used to measure mRNA expression of the genetic regulators of apoptosis by reverse transcription polymerase chain reaction. In a subset of the animals, once left ventricular failure had been established, the constriction device was deflated to produce unloading of the left ventricle.nnnRESULTSnTen of the 17 sheep banded developed left ventricular failure. Over the first 3-4 weeks, left ventricular mass index increased acutely (88+/-18 vs. 44+/-10 g/m(2), P<0.01) followed by gradual left ventricular dilatation (diastolic left ventricular internal diameter 4.1+/-0.7 vs. 3.2+/-0.3 cm, P<0.01). Ventricular function remained stable until 7-8 weeks postoperatively, when there was significant deterioration (fractional shortening 17+/-8 vs. 40+/-8%, P<0.01) associated with clinical heart failure. Expression of the pro-apoptotic genes (bax and Fas) increased significantly following inflation of the constriction device and persisted through the transition to left ventricular failure. Following deflation of the constriction device, myocardial contractility gradually improved over a 3 week period (fractional shortening 32+/-1 vs. 17+/-8%).nnnCONCLUSIONSnProgressively increasing the afterload on the left ventricle produces a clinical and echocardiographical picture of chronic heart failure. Obtaining myocardial tissue during this transition will allow the molecular correlates of pressure overload-induced heart failure and potential myocardial recovery to be investigated.

Original articleGeneral thoracicComparison of Outcomes From Smoking and Nonsmoking Donors: Thirteen-Year Experience

BACKGROUNDnLung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD).nnnMETHODSnThis study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection.nnnRESULTSnDuring this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans.nnnCONCLUSIONSnIn this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs.

Infant partial left ventriculectomy for failure to wean from cardiopulmonary bypass

Following aortic reimplantation of anomalous left coronary artery from the pulmonary artery in a 6-month-old infant, the heart failed to wean after prolonged supportive cardiopulmonary bypass and maximal inotropic support. We performed partial left ventriculectomy (Batista procedure) that halved left atrial pressure and enabled discontinuation of bypass. Postoperative recovery was then uneventful.