A feasibility and safety study of intracoronary hemodilution during primary coronary angioplasty in order to reduce reperfusion injury in myocardial infarction.

OBJECTIVES: We designed a pilot study to evaluate safety and feasibility of an inexpensive and simple approach to intracoronary hemodilution during primary angioplasty (PPCI) to reduce reperfusion injury. INTRODUCTION: Early revascularization in acute myocardial infarction decreases infarct size and improves outcomes. However, abrupt restoration of coronary flow results in myocardial reperfusion injury and increased final infarct size. Dilution of coronary blood during revascularization may help reduce this damage. If proved effective, such an approach would need to be simple and suitable for widespread adoption. METHODS: Ten patients presenting with STEMI underwent intracoronary dilution with room temperature Hartmann's solution delivered through the guiding catheter during primary angioplasty (PPCI). Infusion of perfusate began prior to crossing the occluded artery with the guidewire, continuing until 10 min after completion of the balloon and stenting procedure. Infusion was briefly interrupted for contrast injection and pressure monitoring. The outcome measures were safety, including intracoronary temperature reduction and volume of intracoronary perfusate infused, and technical feasibility. RESULTS: There were no significant symptomatic, hemodynamic, ECG ST/T segment or rhythm changes observed during perfusate administration. The median (interquartile range) volume of perfusate administered was 550 mL (350-725 mL) and the median intracoronary temperature reduction observed was 3.4°Celsius. Myocardial salvage was 0.54 (0.43-0.65). CONCLUSIONS: Transcatheter intracoronary hemodilution with room temperature perfusate during PPCI is feasible and appears safe. Such a strategy is simple and inexpensive, with potential to be widely applied. Further mechanistic and subsequent outcome powered studies are required to evaluate whether this strategy can reduce reperfusion injury in STEMI.

High incidence of acute coronary occlusion in patients without protocol positive ST segment elevation referred to an open access primary angioplasty programme.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) programmes vary in admission criteria from open referral to acceptance of electrocardiogram (ECG) protocol positive patients only. Rigid criteria may result in some patients with acutely occluded coronary arteries not receiving timely reperfusion therapy. OBJECTIVE: To compare the prevalence of acute coronary occlusion and, in these cases, single time point biomarker estimates of myocardial infarct size between patients presenting with protocol positive ECG changes and those presenting with less diagnostic changes in the primary angioplasty cohort of an open access PPCI programme. METHODS: We retrospectively performed a single centre cross sectional analysis of consecutive patients receiving PPCI between January and August 2008. Cases were categorised according to presenting ECG-group A: protocol positive (ST segment elevation/left bundle branch block/posterior ST elevation myocardial infarction), group B: ST segment depression or T-wave inversion, or group C: minor ECG changes. Clinical characteristics, coronary flow grades and 12 h postprocedure troponin-I levels were reviewed. RESULTS: During the study period there were 513 activations of the PPCI service, of which 390 underwent immediate angiography and 308 underwent PPCI. Of those undergoing PPCI, 221 (72%) were in group A, 41 (13%) in group B and 46 (15%) in group C. Prevalence of coronary occlusion was 75% in group A compared with 73% in group B and 63% in group C. Median 12 h postintervention troponin-I (25th-75th percentile) for those with coronary occlusion was significantly higher in group A patients; 28.9 µg/l (13.2-58.5) versus 18.1 µg/l (6.7-32.4) for group B (p=0.03); and 15.5 µg/l (3.8-22.0) for group C (p<0.001), suggesting greater infarct size in group A. CONCLUSIONS: A number of patients referred to an open access PPCI programme have protocol negative ECGs but myocardial infarction and acute coronary artery occlusion amenable to angioplasty.

Defining the role of recombinant activated factor VII in pediatric cardiac surgery: where should we go from here?

OBJECTIVES: Postoperative hemorrhage is a recognized complication of pediatric cardiac surgery. Both the immature coagulation system and increased susceptibility to hemodilution increase the likelihood of pediatric patients developing coagulopathy when compared with adult counterparts. Treatment options remain limited. Recombinant factor VII (rFVIIa) is a hemostatic agent increasingly used to reduce hemorrhage in other surgical settings, the role of which is unclear in this population. This article systematically reviews the published literature on the use of rFVIIa in pediatric cardiac surgery. DATA SOURCES AND STUDY SELECTION: A systematic literature search identified reports of rFVIIa administration in pediatric patients undergoing cardiac surgery. Where possible, individual patient-specific data were extracted and pooled statistical analysis was performed. DATA EXTRACTION AND SYNTHESIS: Twenty-nine articles reporting on the administration of rFVIIa to 169 patients were identified. rFVIIa has been administered to patients with predefined congenital abnormalities of hemostasis to arrest hemorrhage refractory to other interventions and prophylactically in the hope of reducing blood loss. Treatment regimens vary widely, in terms of both first and cumulative dose. Data on chest tube blood loss and two markers of coagulation were pooled and analyzed, and significant improvements were demonstrated. Mortality was 4.4% for the entire cohort but 20% of patients on extracorporeal membrane oxygenation suffered significant thromboembolic complications. CONCLUSIONS: rFVIIa has an increasingly accepted role in the management of patients with congenital coagulopathies undergoing major surgery. However, randomized trials are required to define the role of rFVIIa as an adjunct to control major hemorrhage in the pediatric cardiac surgical population. Any future work must focus not only on benefits but also on patient safety, particularly, risk of morbid thromboembolic complication.

Exercise-based cardiac rehabilitation for patients following open surgical aortic valve replacement and transcatheter aortic valve implant: a systematic review and meta-analysis.

Objectives: Exercise-based cardiac rehabilitation (CR) may be beneficial to patients following transcatheter aortic valve implantation (TAVI) and open surgical aortic valve replacement (SAVR). We aimed to undertake a systematic review and meta-analysis to evaluate the efficacy, safety and costs of exercise-based CR post-TAVI and post-SAVR. Methods: We searched numerous databases, including Embase, CENTRAL and MEDLINE, up to October 2017. We included randomised controlled trials (RCTs) and non-randomised controlled trials (non-RCTs) of exercise-based CR compared with no exercise control in TAVI or SAVR patients ≥18 years. Data extraction and risk of bias assessments were performed independently by two reviewers. Narrative synthesis and meta-analysis (where appropriate) were carried out for all relevant outcomes, and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis was also performed. Results: Six studies, all at low risk of bias, were included: three RCTs and three non-RCTs (total of 27 TAVI, 99 SAVR and 129 mixed patients), with follow-up of 2-12 months. There was an increase in pooled exercise capacity (standardised mean difference: 0.41, 95% CI 0.11 to 0.70; moderate certainty evidence as assessed by GRADE), with exercise-based rehabilitation compared with control. Data on other outcomes including quality of life and clinical events were limited. Conclusions: Exercise-based CR probably improves exercise capacity of post-TAVI and post-SAVR patients in the short term. Well conducted multicentre fully powered RCTs of ≥12 months follow-up are needed to fully assess the clinical and cost-effectiveness of exercise-based CR in this patient population. PROSPERO Protocol Registration Number: CRD42017084716.

Cardiac rehabilitation to improve health-related quality of life following trans-catheter aortic valve implantation: a randomised controlled feasibility study: RECOVER-TAVI Pilot, ORCA 4, For the Optimal Restoration of Cardiac Activity Group.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is often undertaken in the oldest frailest cohort of patients undergoing cardiac interventions. We plan to investigate the potential benefit of cardiac rehabilitation (CR) in this vulnerable population. DESIGN: We undertook a pilot randomised trial of CR following TAVI to inform the feasibility and design of a future randomised clinical trial (RCT). PARTICIPANTS: We screened patients undergoing TAVI at a single institution between June 2016 and February 2017. INTERVENTIONS: Participants were randomised post-TAVI to standard of care (control group) or standard of care plus exercise-based CR (intervention group). OUTCOMES: We assessed recruitment and attrition rates, uptake of CR, and explored changes in 6-min walk test, Nottingham Activities of Daily Living, Fried and Edmonton Frailty scores and Hospital Anxiety and Depression Score, from baseline (30 days post TAVI) to 3 and 6 months post randomisation. We also undertook a parallel study to assess the use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the post-TAVI population. RESULTS: Of 82 patients screened, 52 met the inclusion criteria and 27 were recruited (3 patients/month). In the intervention group, 10/13 (77%) completed the prescribed course of 6 sessions of CR (mean number of sessions attended 7.5, SD 4.25) over 6 weeks. At 6 months, all participants were retained for follow-up. There was apparent improvement in outcome scores at 3 and 6 months in control and CR groups. There were no recorded adverse events associated with the intervention of CR. The KCCQ was well accepted in 38 post-TAVI patients: mean summary score 72.6 (SD 22.6). CONCLUSIONS: We have demonstrated the feasibility of recruiting post-TAVI patients into a randomised trial of CR. We will use the findings of this pilot trial to design a fully powered multicentre RCT to inform the provision of CR and support guideline development to optimise health-related quality of life outcomes in this vulnerable population. Retrospectively registered 3rd October 2016 clinicaltrials.gov NCT02921880. TRIAL REGISTRATION: Clinicaltrials.Gov identifier NCT02921880.

A collaborative clinic between contraception and sexual health services and an adult congenital heart disease clinic.

BACKGROUND: The success of cardiac surgery has created a new group of patients: those with 'adult congenital heart disease' (CHD) who may need specialist advice about contraception and pregnancy. The study objective was to investigate whether women with CHD were receiving appropriate advice on contraception. METHODS: The study setting comprised a combined adult CHD and contraception and sexual health clinic operating alongside each other, once a month, at Freeman Hospital, Newcastle-upon-Tyne, UK. Data were collected on 46 consecutive female patients attending the clinic between April 2002 and October 2003. RESULTS: Sixteen of the 46 (35%) women had never discussed contraception with a health professional. Nine of these women were sexually active and were using condoms. Seven of these women chose to start hormonal contraception following consultation. Ten of the 30 (33%) women who had previously discussed contraception with either their general practitioner or family planning clinic had received inappropriate advice. Of these 30 women, 24 needed contraception: 12 (50%) continued with their current method, 10 (42%) started hormonal contraception having previously used either condoms or no contraception and two (8%) changed their current hormonal method to a more effective long-term method (progestogen-only pill to progestogen implant). There had been eight unplanned pregnancies in seven patients. There was poor knowledge among the women about long-acting hormonal methods, particularly progestogen injectables and implants. CONCLUSIONS: Our experience has highlighted the substandard provision of sexual health services for adults with CHD. Many of these women receive either no advice or inappropriate advice about contraception. Suitable effective reversible methods are often denied by health professionals who are concerned about the safety of hormonal contraceptives in women with 'heart problems'. Preconception advice and birth control information should be given to all female patients with CHD, as correct information will avoid the potential risks of an unplanned pregnancy. A monthly regional combined clinic staffed by a cardiologist and family planning doctor provides the ideal opportunity for education of patients and health professionals alike. Good practice is then disseminated across specialities and into the community, encouraging multidisciplinary guidelines and pathways of referral to be developed.

Safety and tolerability of bosentan in adults with Eisenmenger physiology.

BACKGROUND: Bosentan, a dual-endothelin receptor antagonist, is an established treatment for pulmonary arterial hypertension. We hypothesized that bosentan is safe and well tolerated in patients with Eisenmenger physiology. METHODS: In this pilot open-label study, we primarily examined safety and tolerability of oral bosentan. Patients were recruited from our adult congenital heart clinic following informed consent. Baseline and 3-month assessment included WHO functional class, resting oxygen saturations, 6-min walk test, transthoracic echocardiography and respiratory mass spectrometry. Patient clinical status and liver enzymes were closely monitored throughout. RESULTS: All 10 study patients (42+/-4 years; eight female) tolerated bosentan well. No major adverse events or significant liver enzyme elevations were observed. All but one patient felt better; none felt worse. Four patients experienced transient leg oedema. Resting oxygen saturations (83+/-5 versus 80+/-5%; P=0.011) and the distance travelled in the 6-min walk test (348+/-112 versus 249+/-117 m; P=0.004) increased relative to baseline. Changes in echocardiographic parameters (maximum aortic forward flow velocity 1.3+/-0.1 versus 1.1+/-0.2 ms, P=0.013; pulmonary arterial acceleration time 66+/-10 versus 58+/-12 m/s, P=0.02) and pulmonary blood flow (3.45+/-1.2 versus 2.58+/-1.0 L/min, P=0.008) suggested improved pulmonary haemodynamics by study end. Other echocardiographic changes suggested improved right ventricular systolic function (septal amplitude 1.0 versus 1.1 cm, P=0.048; systolic tissue Doppler velocity 4.8 versus 2.3 cm s(-1), P=0.002) by study end. CONCLUSIONS: Bosentan was safe and well tolerated in adults with Eisenmenger physiology both at initiation and after 3 months of oral therapy. Clinical status of patients and pulmonary haemodynamics appeared to improve, and this warrants further investigation.

Inter-hospital transfer for primary angioplasty: delays are often due to diagnostic uncertainty rather than systems failure and universal time metrics may not be appropriate.

AIMS: We aimed to investigate why many patients with ST-segment elevation myocardial infarction (STEMI) initially present to non-primary percutaneous coronary intervention (PPCI) equipped hospitals in a region that offers a 24-hour direct access Heart Attack Centre. METHODS AND RESULTS: A retrospective stratified consecutive case analysis was performed for 180 inter-hospital transfer (IHT) and 201 direct access PPCI patients. IHT and direct patients had similar age (61±1.8 years vs. 62±1.9 years, p=0.42), gender (76% vs. 78% male, p=0.64), and cardiovascular risk profile (hypertension 53% vs. 46%, p=0.18; hypercholesterolaemia 32% vs. 25%, p=0.22; and smoking 38% vs. 35%, p=0.56), though there were more diabetic patients in the IHT group (15% vs. 8%, p<0.05). The IHT group had longer symptom-call times 104 mins (42 mins-195 mins) vs. 46 mins (19 mins-114 mins), p<0.0001), lower ECG ST-elevation scores (3.0 mm [1.0-6.0] vs. 5.0 mm [3.0-9.0], p<0.0001), and more protocol negative ECGs at presentation (31.6% vs. 9.4%, p<0.0001). Peak CK was similar for the two groups (628 IU/L [191-1,144] vs. 603 IU/L [280-1,238], p=0.61), as was in-hospital (1.7% vs. 1.5%, p=0.89) and 30-day mortality (2.8% vs. 2.0%, p=0.61). CONCLUSIONS: This study suggests that reperfusion delays in PPCI due to IHT are not always simply "system failures". IHT patients appear to be a different patient cohort in which symptoms and early ECG changes may be less clear. In many cases, initial triage to a non-PPCI centre may be justifiable due to diagnostic uncertainty, and guideline time metrics should be amended appropriately.

Pulmonary hypertension.

Pulmonary hypertension (PH) is a rare blood vessel disorder of the lung, in which the pressure in the pulmonary artery rises above normal levels and can become life-threatening. The authors discuss the disease process, symptoms, investigations and patient management.

Care of patients with heart failure and the use of ventricular assist devices.

Heart failure is becoming increasingly common as the population ages. Ventricular assist devices are used as a bridge for patients whose heart failure can no longer be controlled by medication and require a heart transplant. This article examines the care, rehabilitation and education of these patients.

International survey of enteral nutrition protocols used in children with Crohn's disease.

OBJECTIVE: Differing protocols have been utilized in published studies evaluating exclusive enteral nutrition (EEN) in the management of active pediatric Crohn's disease. This study aimed to ascertain the protocols currently utilized in different pediatric centers around the world and to highlight their similarities and differences. METHODS: A questionnaire was circulated to individuals at pediatric centers in countries in Europe, North America and Asia-Pacific. Respondents were asked to indicate the number of children treated with EEN at their centers in the previous years and to provide details of their protocol used for administering EEN to these children. RESULTS: Responses were received from 35 separate centers (42% of those asked). The duration of EEN varied from <6 weeks to >12 weeks, but was most commonly 6 to 8 weeks. Although 23 different formulas were utilized across the centers, most (90%) used polymeric formulas. Flavourings were commonly added to formulas but wide variations existed between centers with the prescription of food and fluids permitted during the EEN period. The reintroduction of food after EEN also varied greatly: the most common recommendations were for an initial low-fiber diet (26%) or the gradual introduction of food quantity as the formula volume decreased (52%). CONCLUSIONS: This questionnaire-based study has shown the wide variations in EEN protocols used in different areas of the world. The development of consistent protocols may enhance the acceptance, efficacy and wider utilization of this therapy.

Effect of ABCB1 genotype on pre- and post-cardiac transplantation plasma lipid concentrations.

Genetic variation of ATP-binding cassette subfamily B member 1 (ABCB1) which encodes P-glycoprotein (P-gp) has been associated with lipid levels and response to statins. Here, we studied these associations in patients with advanced heart failure who subsequently underwent transplantation. Fasting total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) concentrations in 268 adult heart transplant recipients were analysed retrospectively before and at 1 year after transplantation (n = 176). ABCB1 genotyping and haplotyping for C1236T, G2677T/A and C3435T was performed using polymerase chain reaction. Pre-transplant LDL cholesterol was found to be associated with the C3435T genotype and the G2677T/A-C3435T and C1236T-G2677T/A-C3435T haplotypes. T-allele carriers at all loci (n = 77) had higher LDL levels than non-T-allele carriers (n = 24, 3.5 ± 1.2 vs. 2.8 ± 1.2 mmol/L, respectively, p = 0.025). This association remained after adjustment for age, sex, body mass index, statin use and underlying ischaemic heart disease. ABCB1 genotype was not associated with post-transplant lipid parameters. Hypercholesterolaemia (TC >5.7 mmol/L) was more prevalent post-transplant than pre-transplant (51% vs. 30%, respectively) and was likely related to steroid and calcineurin inhibitor use. Muscle-related statin effects were only seen in patients possessing the T-haplotype. In conclusion, an association between ABCB1 haplotype and plasma fasting LDL cholesterol concentration was found in patients with advanced heart failure. This association was not seen 1 year after cardiac transplantation.

How minimalized extracorporeal circulation compares with the off-pump technique in coronary artery bypass grafting.

Recognition of the adverse effects of conventional extracorporeal circulation (CECC) led to the development of alternative technologies and techniques to minimize their impact while maintaining circulation during coronary artery bypass grafting (CABG). Off-pump coronary artery bypass (OPCAB) grafting has become established as one such alternative and more recently minimalized extracorporeal circulation (MECC) circuits have been developed with the aim of providing circulatory support while minimizing the interface between blood and the foreign surfaces of the circuit that initiates the associated adverse effects of CECC. Recently, some authors have suggested that MECC may be an alternative to OPCAB in patients undergoing CABG; the aim of this article is to systematically analyze and compare the impact of CABG with MECC with that of OPCAB, studying the adverse outcomes related to CECC. We performed a systematic search to identify all studies directly comparing OPCAB and MECC. Endpoints were subcategorized into four key areas of interest: length of stay (LOS), hemorrhage, cerebrovascular injury, and 30-day mortality. Random effect modeling techniques were applied to identify differences in outcomes between the two groups. Six studies fulfilled the inclusion criteria, incorporating 2,072 patients of whom 930 underwent OPCAB and 1,142 underwent revascularization supported by MECC. We found no statistically significant difference in hospital or intensive care unit (ICU) LOS, blood loss, mean number of patients transfused, neurocognitive disturbance, or 30-day mortality between the two groups but a trend toward an increased number of cerebrovascular events in the MECC group was observed. The number of studies comparing these alternative techniques for coronary revascularization is small, and there is a lack of high-quality data. Currently, there seems little difference between MECC and OPCAB but larger randomized controlled trials focusing on high-risk patients are required.

Effect of adenosine monophosphate deaminase-1 C34T allele on the requirement for donor inotropic support and on the incidence of early graft dysfunction after cardiac transplantation.

The C34T T allele of the adenosine monophosphate deaminase-1 (AMPD1) gene has been associated with improved outcome in patients with cardiac dysfunction. We hypothesized that possession of this allele by donor hearts plays a role in the outcome of cardiac transplantation; 262 cardiac donors and 190 of their recipients were studied. AMPD1 C34T genotype was determined using 5' exonuclease chemistry. Requirement for inotropic agents before organ donation, 1-year post-transplantation survival, cause of death, and factors known to affect survival after transplantation were also studied. Multiple regression models for factors affecting survival were constructed. A significant yearly increase in frequency of the T allele in donors was noted (0.06 to 0.18 from 1994 to 1999). Donors with the CT or TT genotype required less inotropic support than those with the CC genotype (mean number of inotropes per donor with CT or TT genotype 0.27 compared with 0.47 per donor with CC genotype, n = 206, p = 0.03). Recipients of T-allele-carrying organs showed worse 1-year survival after transplantation (59% vs 79%, p <0.001). Excess deaths in these patients was due to early graft dysfunction (odds ratio for early graft dysfunction 6.6, 95% confidence interval 2 to 21.6, p = 0.0001). Multivariate analysis showed donor AMPD1 genotype, recipient age, and pretransplantation anemia to independently affect 1-year post-transplantation survival (adjusted hazard ratios 3.7, 1.06, and 2.6, respectively). In conclusion, possession of the AMPD1 T allele is associated with decreased inotropic requirements before heart donation. The incidence of early graft dysfunction, however, was significantly higher in recipients who received AMPD1 T-allele-possessing organs resulting in worse 1-year survival.

The effects of pre- and post-transplant anemia on 1-year survival after cardiac transplantation.

BACKGROUND: Anemia is associated with a poor prognosis in heart failure. Recent studies have also suggested that anemia may be a predictor of survival after heart transplantation. METHODS: We investigated whether anemia before or after orthotopic cardiac transplantation affected post-transplant survival and analyzed data from a historical cohort of 267 consecutive adult patients who underwent transplantation between 1994 and 1999. Hemoglobin levels immediately before and at 6 weeks after orthotopic cardiac transplantation were recorded. Anemia was defined as a hemoglobin level less than 12 g/dl. The outcome was all-cause mortality. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Pre-transplant anemia was present in 26% (n= 70). One-year survival was 70% in subjects who were anemic before transplantation compared with 81% in those who were not (p = 0.03). Multivariate analysis showed a 1-year mortality hazard ratio for pre-transplant anemic subjects of 1.77 (95% confidence interval, 1.03 3.0, p = 0.038). Anemia was more prevalent after transplantation (78%). There was no difference in 1-year survival between post-transplant anemic and non-anemic subjects. CONCLUSION: Anemia before, but not after transplantation, is a common independent predictor of 1-year survival in cardiac transplant patients.

Bridge to decision using the Levitronix CentriMag short-term ventricular assist device.

BACKGROUND: Ventricular assist devices are effective in severe end-stage cardiac failure but outcomes remain poor in critically ill patients. Cheaper and less invasive short-term devices have been used in this setting. We report our experience with the Levitronix CentriMag short-term ventricular assist device as a potential bridge prior to deciding whether a more expensive device should be used or whether transplantation should be undertaken. METHODS: Since August 2003, 16 moribund patients (14 males; age 32.7 +/- 14.9 [range 16 to 62] years) have been supported with the CentriMag device as a "bridge to decision." Twelve patients had an intra-aortic balloon pump pre-operatively, 13 had multi-organ failure, 11 had septic shock, and in 5 patients the neurologic status was uncertain at the time of insertion of the device. RESULTS: Operative mortality was 18.7% (3 patients). Seven patients (43.7%) were reoperated for bleeding. The mean support duration was 46.9 +/- 32.3 (range 6 to 111) days. There were 2 late deaths during Levitronix utilization. Follow-up was 12.8 +/- 12.5 (range 0.6 to 43) months. Eleven patients (68.7%) are currently alive and well: 2 patients recovered and had the Levitronix device explanted; 6 patients were upgraded to a long-term device; and 3 patients were bridged directly to transplantation. The actuarial survival at 1, 6 and 12 months was 85.7%, 64.9% and 64.9%, respectively. There were no instances of device failure. CONCLUSIONS: The Levitronix device is effective in rescuing critically ill "moribund" patients and can provide an opportunity for low-cost support and optimization of their condition prior to deciding whether a more expensive device should be placed or if transplantation should be undertaken. Better candidate selection for further procedures can then be allowed.

Quality of life after removal of left ventricular assist device for myocardial recovery.

BACKGROUND: Longer term quality of life (QOL) outcome in patients who have had a left ventricular assist device (LVAD) explanted due to myocardial recovery (bridge to recovery, BTR) remains uncertain. This study evaluates the QOL of those patients and compares them to bridge-to-transplant (BTT) and transplanted (Tx) patients. METHODS: Anonymized QOL Short Form (SF)-36 questionnaires were sent to a total of 72 patients, including: 14 BTR patients (3.6 +/- 1.9 years since LVAD removal); 29 BTT patients (3.3 +/- 2.3 years since transplantation); and 29 Tx patients (3.8 +/- 0.6 years since transplantation). RESULTS: Questionnaires were returned by 78.6%, 79.3% and 56.7% of patients from the BTR, BTT and Tx groups, respectively. In all but two of the domains of the SF-36 questionnaire, scores were significantly better in the BTR group compared with the BTT and Tx groups. Analysis of the two main dimensions and the total SF-36 score between the three groups showed that: (i) physical health dimension tended to be better in BTR (71.9 +/- 21) vs BTT (64.5 +/- 23.2) and Tx (41.4 +/- 48) groups (p = not statistically significant [NS]); (ii) mental health dimension was better in both BTR (78 +/- 16.1) and BTT (71.4 +/- 21.1) groups compared with the Tx group (39.4 +/- 44, p < 0.05); and (iii) total SF-36 score was significantly higher in the BTR and BTT groups compared with the Tx group (76.8 +/- 17.6 and 69 +/- 21.1 vs 41.4 +/- 48, p = NS). CONCLUSIONS: BTR patients appear to have better QOL than both BTT and Tx patients. In addition, BTT patients seem to have a better QOL compared with Tx patients, suggesting that placement of ventricular assist devices could improve the physiologic outcome for transplanted patients.

Midterm experience with the Jarvik 2000 axial flow left ventricular assist device.

OBJECTIVE: Rotary axial flow pumps have several potential advantages and disadvantages over pulsatile pumps. The Jarvik 2000 is distinctive in being intracardiac. We report our experience in 22 patients. METHODS: The Jarvik 2000 was implanted in 15 men and 7 women. Mean age was 38.8 (range 23-59) years, preoperative diagnosis was dilated cardiomyopathy in 16, postpartum cardiomyopathy in 3, ischemic heart disease in 2, and chronic allograft failure in 1. Twenty-one patients were in New York Heart Association class IV, and 1 patient was in class III. Nineteen patients were on inotropic support, 6 were supported with an intra-aortic balloon pump, and 2 patients had been salvaged with a Centrimag (Levitronix) ventricular assist device. The median pulmonary vascular resistance was 3 Wood units; median pulmonary capillary wedge pressure was 26.6 mm Hg; and mean Cardiac Index was 1.5 L/min/m2. RESULTS: There were 2 early deaths and 6 late deaths. The average postoperative ventilation time and Intensive Treatment Unit stay was 2.2 and 10 days, respectively. One patient required a right ventricular assist device for short-term support and another for medium-term support. Seven patients were bridged to transplant, 3 had myocardial recovery, and 4 are ongoing. Mean and total duration of support was 280.5 and 6172 days, respectively. Driveline failures were noted in 3, but there were no pump infections or failure. CONCLUSION: The Jarvik 2000 provides satisfactory intermediate-term results as a bridge to transplant or recovery. It appears to be associated with a low rate of serious driveline or pump infections and technical failure. However, bleeding complications due to the required anticoagulation treatment frequently occurred.

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer.

OBJECTIVES: Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). Incomplete local control and the appearance of distant disease herald poor survival and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in vitro radiosensitization, and are cytotoxic in weekly schedules. This study was done to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly paclitaxel/carboplatin chemoradiotherapy in locally advanced cervix cancer. METHODS: Women with primary, previously untreated, squamous cell or adenocarcinoma of the cervix, FIGO stage IB(2) to IVA, negative para-aortic lymph nodes, adequate organ function and performance status were eligible. Pelvic RT (45 Gy over 5 weeks--180 cGy/day, four-field) was followed by two brachytherapy applications (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurrent weekly CT was paclitaxel 50 mg/m(2) and carboplatin, starting at AUC 1.5 and escalating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation followed a 4-week observation period for toxicity. A grade III-IV toxicity prompted up to three additional patients per dose level. A second event defined DLT. CT was administered concurrently throughout brachytherapy. RESULTS: Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23-70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT treatment time was 61 days (range, 55-79). Fourteen patients received brachytherapy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis. The median number of weekly CT cycles was seven (range, 6-7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was observed at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III-IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III anemia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitaxel 50 mg/m(2). Median follow-up is 17 months; three patients have recurred and two have died. The estimated 2-year PFS and OS are 80% and 86%. CONCLUSIONS: Weekly paclitaxel and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m(2) and AUC 2.5, respectively.