Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction. Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome. Reduction of blood utilization during myocardial revascularization. Case management in a heterogeneous congestive heart failure population: a randomized controlled trial. Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. [Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function]. WHO European Collaborative Trial of multifactorial prevention of coronary heart disease. Impact of care at a multidisciplinary congestive heart failure clinic: a randomized trial. Serum cholesterol, lifestyle, working capacity and quality of life in patients with coronary artery disease. Experiences from a hospital-based secondary prevention programme. Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial. Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient. The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). Exercise training intervention after coronary angioplasty: the ETICA trial. Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI). Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction. A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Randomized, controlled evaluation of short- and long-term benefits of heart failure disease management within a diverse provider network: the SPAN-CHF trial. Efficacy of an intensive prevention program in coronary patients in primary care, a randomised clinical trial. A prospective randomized trial of preoperative "optimization" of cardiac function in patients undergoing elective peripheral vascular surgery. Effect of local medical opinion leaders on quality of care for acute myocardial infarction: a randomized controlled trial. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure. Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft. High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial.
There are only few data on long-term effectiveness of the stem cell therapy.
                We studied the time course of global and regional left ventricular function in patients with acute myocardial infarction within 1 year after the autologous mononuclear bone marrow cell transplantation.
                Sixty patients with a first acute myocardial infarction, who had been randomized into 3 groups, completed a 12-month protocol. Two groups were intracoronarily given bone marrow cells in either higher (10(8) cells, HD group, n=20) or lower (10(7) cells, LD group, n=20) doses. Twenty patients without cell transplantation served as a control (C) group. Doppler tissue imaging and the gated technetium-99m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3, 6, and 12 months later.
                The baseline peak systolic velocities of longitudinal contraction of the infarcted wall (S(infarct)) of 5.2 cm/s, 4.6 cm/s, and 4.4 cm/s in C, LD, and HD groups increased by 0.0 cm/s, 0.3 cm/s (p=NS vs. C group), and by 0.7 cm/s (p<0.05 vs. C group), respectively, at 3 months. At 12 months, however, the corresponding changes from baseline values of 0.1 cm/s, 0.2 cm/s, and 0.6 cm/s did not differ significantly (all p=NS). In contrast, the post-transplant improvements in the left ventricular ejection fraction by 6%, 7%, and 7% at months 3, 6, and 12, respectively, were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls.
                In our study, the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infarction. However, when evaluating regional systolic function of the infarcted wall, the short-term benefit was partially lost during the 12-month follow-up. To evaluate the safety profile and efficacy of bone marrow mononuclear cells (BMMNC) transplantation for ST-segment elevation myocardial infarction (STEMI) by assessing patients and their left ventricular function at up to 4 years follow-up.
                Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were randomized to receive intracoronary injection of BMMNC (n = 41) or saline (n = 45). Left ventricular ejection fraction, as evaluated by UCG, was markedly improved at 6 months (0.484 +/- 0.5 vs. 0.457 +/- 0.6, P = 0.001), 1 year (0.482 +/- 0.7 vs. 0.446 +/- 0.6, P < 0.001), and 4 years (0.505 +/- 0.8 vs. 0.464 +/- 0.8, P < 0.001) after BMMNC transplant when compared with control group. However, the current cell therapy did not improve the myocardial viability of the infarcted area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant (0.263 +/- 0.007 in BMMNC group vs. 0.281 +/- 0.008 in control group, P = 0.10). During the follow-up period, one control group case (2.2%) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI. Also during follow-up, one death (2.2%) occurred in the control group, and one patient (2.4%) in the BMMNC group had transient acute heart failure.
                This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI, and can lead to long-term improvement in myocardial function. It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF).
                To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165).
                Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome. The efficacy of four different blood conservation techniques in decreasing the homologous blood requirement in cardiac operations was studied prospectively in 100 patients undergoing myocardial revascularization. The patients were randomly assigned to four groups of 25 each as follows: group I, retransfusion of oxygenator blood after termination of extracorporeal circulation; group II, processing of oxygenator content by means of a cell separator; group III, predonation of autologous blood and isovolumetric substitution of hydroxyethyl starch (10 ml/kg bodyweight) after the induction of anesthesia in addition to the use of a cell separator; and group IV, predonation and the use of a cell separator plus postoperative retransfusion of shed mediastinal blood. To form homologous groups, we accepted only male patients without impairment of left ventricular function for the study. In addition, patients with internal mammary artery grafts and a duration of extracorporeal circulation less than 45 minutes or more than 90 minutes were excluded. The bank blood requirement during hospitalization was 2132 +/- 824 ml in group I, 1371 +/- 928 ml in group II, 833 +/- 599 ml in group III, and 408 +/- 559 ml in group IV. The use of blood conservation techniques resulted in reductions of homologous blood requirements of 34%, 60%, and 80%, respectively, in groups II to IV as compared with the requirement in group I. There were no complications related to autologous blood transfusion. We conclude that the use of blood conservation techniques can considerably reduce the homologous blood requirement in cardiac operations and therefore decrease transfusion-related risks. Both randomized and nonrandomized controlled studies have linked congestive heart failure (CHF) case management (CM) to decreased readmissions and improved outcomes in mostly homogeneous settings. The objective of this randomized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting.
                A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF, left ventricular dysfunction of less than 40%, or radiologic evidence of pulmonary edema for which they underwent diuresis were randomized. The intervention consisted of 4 major components: early discharge planning, patient and family CHF education, 12 weeks of telephone follow-up, and promotion of optimal CHF medications.
                The 90-day readmission rates were equal for the CM and usual care groups (37%). Total inpatient and outpatient median costs and readmission median cost were reduced 14% and 26%, respectively, for the intervention group. Patients in the CM group were more likely to be taking CHF medication at target doses, but dosages did not increase significantly throughout 12 weeks. Although both groups took their medications as prescribed equally well, the rest of the adherence to treatment plan was significantly better in the CM group. Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group (P =.03).
                These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting. One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended, nonnetworked physician setting limits the effectiveness of the CM. To examine the kinetics of volume loading with crystalloid and colloid infusions in critically ill patients after major surgery, using the pulse contour cardiac output (PiCCO) monitoring technique.
                This prospective, randomized, multicentre study of 11 ICUs involved 200 mixed postoperative hypovolaemic patients (50 patients per group) in Hungary. Patients received 10 ml kg of lactated Ringer's solution, succinylated gelatin 4% w/v, 130/0.4 hydroxyethyl starch 6% w/v (HES) or human albumin 5% w/v over 30 min. A complete haemodynamic profile was obtained at 30, 45, 60, 90 and 120 min after baseline. The peak haemodynamic effects, the 120 min changes compared with baseline, the area under the curve (AUC) for the haemodynamic parameters over 120 min and the haemodilution effect of the solutions were analysed. The primary outcome was to compare the AUCs and the secondary outcome was to evaluate the haemodynamic changes at 120 min.
                There were significant differences in the AUCs of the haemodynamic parameters between colloids and lactated Ringer's solution in the cardiac index and global end-diastolic volume index (GEDVI); human albumin vs. lactated Ringer's solution in stroke volume variation (SVV); and succinylated gelatin, HES vs. lactated Ringer's solution in the oxygen delivery index (DO2I). Colloid infusions (mainly HES and human albumin) at 120 min caused significant changes in central venous pressure, cardiac index, GEDVI, SVV, DO2I and central venous oxygen saturation compared with baseline. The haemodilution effect was significantly greater in colloids vs. lactated Ringer's solution.
                In postoperative hypovolaemic patients, lactated Ringer's solution can significantly improve haemodynamics at the end of volume loading, but this effect completely disappears at 120 min. Ten millilitres per kilogram of colloid bolus (especially HES) improved the haemodynamics at 120 min; however, this was by only 5-25% compared with baseline. The colloids caused significantly larger AUCs than lactated Ringer's solution, but only in the cardiac index, GEDVI and DO2I, plus human albumin in the SVV. It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not.
                Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up.
                A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively.
                Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery. Results are reported from a trial of multifactorial prevention of coronary heart disease (CHD) in occupational groups, involving randomization of 66 factories to intervention and control (49,781 men ages 40 to 59) in the United Kingdom, Belgium, Italy, and Poland. Net average reductions in the intervention factors were 1.2% (plasma cholesterol), 8.9% (daily cigarettes), 0.4% (weight), 2% (systolic blood pressure), and 11% for a combined risk estimate. Reductions were larger in high-risk men (19% for the combined estimate). Red blood cell fatty acid profiles were substantially changed. There was a net overall reduction of 7.4% in fatal CHD and 2.7% in total deaths. Benefits were larger in centers achieving larger risk factor reductions, and in one country--Belgium--the net decreases in CHD incidence and total deaths were significant at the 5% level. Benefit was at least as great in men with established ECG abnormality. It is concluded that CHD risk in middle-aged men seems to be reducible by simple and cost-effective means. Although multidisciplinary congestive heart failure clinics in the United States appear to be effective in reducing the number of hospital readmissions, it is unclear whether the same benefit is seen in countries such as Canada, where access to both general and specialized medical care is free and unrestricted. We sought to determine the impact of care at a multidisciplinary specialized outpatient congestive heart failure clinic compared with standard care.
                We randomly assigned 230 eligible patients who had experienced an acute episode of congestive heart failure to standard care (n = 115) or follow-up at a multidisciplinary specialized heart failure outpatient clinic (n = 115). The intervention consisted of a structured outpatient clinic environment with complete access to cardiologists and allied health professionals. The primary outcomes were all-cause hospital admission rates and total number of days in hospital at 6 months. The secondary outcomes were total number of emergency department visits, quality of life and total mortality.
                At 6 months, fewer patients in the intervention group had required readmission to hospital than patients in the control group (45 [39%] v. 66 [57%], crude hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.38-0.92. Patients in the intervention group stayed in hospital for 514 days compared with 815 days required by patients in the control group (adjusted HR 0.56, 95% CI 0.35-0.89). The number of patients seen in the emergency department and the total number of emergency department visits were similar in the intervention and control groups. At 6 months, quality of life, which was self-assessed using the Minnesota Living with Heart Failure questionnaire, was unchanged in the control group but improved in the intervention group (p < 0.001). No difference in mortality was observed, with 19 deaths in the control group and 12 in the intervention group (HR 0.61, 95% CI 0.24-1.54).
                Compared with usual care, care at a multidisciplinary specialized congestive heart failure outpatient clinic reduced the number of hospital readmissions and hospital days and improved quality of life. When our results are integrated with those from other, similar trials, multidisciplinary disease management strategies for congestive heart failure are associated with clinically worthwhile improvements in survival. Coronary artery diseases (CAD) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events. The development and evaluation of secondary prevention programmes therefore an important task. This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital, Malmö, Sweden. Four weeks after discharge from the hospital, consecutive male and female patients aged 50-70 years with acute myocardial infarction (AMI) or treated with coronary artery bypass grafting (CABG) surgery were randomised to a hospital organised preventive intervention or to usual follow-up at their general practitioners. In the three studies using this randomised design, 87 (study II), 90 (study IV), and 106 (study V) intervention patients were available for evaluation. In addition, without randomisation, lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients (study I), and quality of life (QL) were estimated by questionnaire at one month and at one year after the event in 266 AMI, 94 CABG, and 16 percutaneous transluminal coronary angioplasty (PTCA) patients (study III). The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients (study II). The intervention also did not show any significant improvement in working capacity in AMI and CABG patients. However, working capacity improved in both intervention and reference CABG patients, most probably due to improved coronary circulation from the surgery (study IV). Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients. This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients (study V). The prevention programme also decreased body mass index significantly in AMI but not in CABG patients (study V). In AMI patients receiving thrombolysis, cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal. In AMI patients not receiving thrombolysis, the lipid estimates from four weeks after the event were slightly, but significantly, above the within 24 hours from onset of symptoms estimates (study I). One month after the event, both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls. One year after the event, patients differed from controls mainly in somatic symptoms (study III). Thus, the intervention programme was most successful in affecting lipid levels and food habits in AMI patients. QL was considerably affected in patients following an cardiac event, especially during the initial recovery phase. In addition, in patients receiving thrombolysis, cholesterol levels estimated four weeks after an AMI are reasonably valid estimates of baseline values and may be used to decide about lipid lowering interventions. To assess the effectiveness of two mechanical methods of blood conservation in reducing the need for allogeneic red blood cells or coagulation products during cardiac surgery.
                Randomised controlled trial.
                Regional cardiac centre in a teaching hospital in Southampton.
                263 adults aged 18-80 years undergoing elective coronary artery bypass surgery entered the study, of whom 252 completed the trial. All patients received routine perioperative care. Patients were allocated to one of three treatment groups: intraoperative cell salvage, intraoperative cell salvage with acute perioperative normovolaemic haemodilution, or no mechanical blood conservation. There were 84 patients in each group.
                Numbers of patients who received allogeneic blood or coagulation products, and the mean number of units of blood transfused per patient.
                Of the patients in the intraoperative cell salvage group, 26 were given a transfusion of allogeneic blood, compared with 43 in the control group (odds ratio 0.43 (95% confidence interval 0.23 to 0.80)). The mean number of units of allogeneic blood transfused per patient in the intraoperative cell salvage group was 0.68 units (SD=1.55), compared with 1.07 (1.56) units in the control group. 32 of the patients in the intraoperative cell salvage group were given any blood product, compared with 47 in the control group (odds ratio 0.47 (0.25 to 0.89); P=0.019). Combining acute perioperative normovolaemic haemodilution with intraoperative cell salvage conferred no additional benefits.
                An intraoperative cell salvage device should be used in elective coronary artery bypass grafting. Pharmacological strategies may achieve further reductions in blood transfusions. Yet further reductions in blood transfusions could be achieved if the lower safe limit of haemoglobin concentration in patients undergoing cardiac surgery were known. In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial.
                Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device.
                A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment.
                HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin. To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).
                70 patients with AMI were allocated to two groups, one was PBSCs transplantation group (n=35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group (n=35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 microg) with the dose of 300-600 microg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up.
                35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0+/-8.2% to 57.1+/-7.8% (P<0.0001), wall motion score index (WMSI) from 1.219+/-0.190 to 1.101+/-0.118 (P<0.0001), left end-systolic volume (ESV) from 63.8+/-23.9 ml to 52.6+/-20.3 ml (P=0.01) and left end-diastolic volume (EDV) from 134.2+/-36.7 ml to 119.2+/-30.3 ml (P=0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV (P=0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1+/-7.8 to 52.6+/-5.7 (P=0.041) and WISM from 1.101+/-0.118 to 1.184+/-0.138 (P=0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed.
                Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up. The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome.
                It is unknown whether ET induces beneficial effects after coronary angioplasty.
                We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group.
                Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001).
                Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate. Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.
                Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).
                G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis. Initial clinical trials from Europe have demonstrated that the administration of bone marrow-derived mononuclear cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (STEMI). However, results from trials performed in the United States have not yet been presented.
                We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following STEMI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery.
                Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2% +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P < .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m(2), P < .01).
                This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following STEMI. The improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.
                2010 Mosby, Inc. All rights reserved. We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.
                Hospital admission for CHF is an important problem amenable to improved outpatient management.
                Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.
                The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.
                This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF. Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery, which increases resource use and health care costs. Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients. Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves. The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit (ICU) stay. Four hundred three elective cardiac surgical patients were enrolled in the study and randomly assigned to either the control or the protocol group. Goals of the protocol group were to maintain SvO(2) >70% and lactate concentration < or =2.0 mmol/L from admission to the ICU and up to 8 h thereafter. Hemodynamics, oxygen transport data, and organ dysfunctions were recorded. The median hospital stay was shorter in the protocol group (6 vs 7 days, P < 0.05), and patients were discharged faster from the hospital than those in the control group (P < 0.05). Discharge from the ICU was similar between groups (P = 0. 8). Morbidity was less frequent at the time of hospital discharge in the protocol group (1.1% vs 6.1%, P < 0.01). Increasing oxygen delivery to achieve normal SvO(2) values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay. Implications: Health care economics has challenged clinicians to reduce costs and improve resource use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease. Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay. Several trials support the usefulness of disease management (DM) for improving clinical outcomes in heart failure (HF). Most of these studies are limited by small sample size; absence of concurrent, randomized controls; limited follow-up; restriction to urban academic centers; and low baseline use of effective medications.
                We performed a prospective, randomized assessment of the effectiveness of HF DM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients with high baseline use of approved HF pharmacotherapy. During a 90-day follow-up, patients randomized to DM experienced fewer hospitalizations for HF [primary end point, 0.55+/-0.15 per patient-year alive versus 1.14+/-0.22 per patient-year alive in control subjects; relative risk (RR), 0.48, P=0.027]. Intervention patients experienced reductions in hospital days related to a primary diagnosis of HF (4.3+/-0.4 versus 7.8+/-0.6 days hospitalized per patient-year; RR, 0.54; P<0.001), cardiovascular hospitalizations (0.81+/-0.19 versus 1.43+/-0.24 per patient-year alive; RR, 0.57; P=0.043), and days in hospital per patient-year alive for cardiovascular cause (RR, 0.64; P<0.001). Intervention patients showed a trend toward reduced all-cause hospitalizations and total hospital days. On long-term (mean, 283 days) follow-up, there was substantial attrition of the 3-month gain in outcomes, with sustained significant reduction only in days in hospital for cardiac cause.
                In a population with high background use of standard HF therapy, a DM intervention, uniformly delivered across varied clinical sites, produced significant short-term improvement in HF-related clinical outcomes. Longer-term benefit likely requires more active chronic intervention, even among patients who appear clinically stable. Most studies that have analysed the effect of secondary prevention of coronary heart disease come from hospitals. Those that are community-based have been conducted mainly by nurses and follow-up was generally too short to show impact on cardiovascular events.
                This is a multi-centre randomised controlled clinical trial in which patients in the intervention group received periodic postal reminders to see their general practitioner every three months during a 3-year follow-up. General practitioners reinforced healthy lifestyle recommendations to patients and reviewed drug therapies at these quarterly intervals. Patients in the control group received usual care.
                A total of 983 patients aged 30-79 were included. During the 3-year follow-up, 67 patients died and 156 experienced a non-fatal cardiovascular event. The event rates and all-cause mortality were similar in the intervention and control groups (24.0% and 23.5%, and 8.1% and 9.9%, respectively). Improvement in quality of life was similar in both groups. Blood pressure and high-density lipoprotein cholesterol were more frequently within recommended levels in the intervention group than in controls: odds ratio 1.63, 95% confidence interval 1.05-2.51, and odds ratio 2.61, 95% confidence interval 1.32-5.18, respectively.
                Intensive secondary prevention conducted by general practitioners may improve long-term blood pressure control and increase high-density lipoprotein cholesterol in patients with stable coronary disease. Previous investigations have suggested that preoperative invasive hemodynamic monitoring with "optimization" of cardiovascular function may favorably affect the outcome among patients undergoing peripheral vascular surgery. The purpose of this study was to evaluate the effect of preoperative optimization of hemodynamic parameters on outcome in patients undergoing aortic reconstruction (AR) or limb salvage procedures (LSP) in a randomized, prospective clinical trial.
                All 72 patients who consented to participate in this study were admitted to the intensive care unit at least 12 hours before operation for placement of a pulmonary artery catheter (PAC). Patients who were randomized to the treatment group (n = 32) were "optimized" by adjusting their hemoglobin concentration, oxygen saturation (SaO2), cardiac output, or afterload until the mixed venous O2 saturation (SvO2) was at least 65%. The control group (n = 40) underwent placement of a PAC and had oxygen transport parameters measured without any attempt to optimize SvO2.
                There were no significant differences between the treatment and control groups with respect to age, gender, type of operation, initial Acute Physiology and Chronic Health Evaluation (APACHE) II score, SvO2, pulmonary artery occlusion pressure, or cardiac index. All treatment patients achieved an SvO2 of at least 65% before operation. Comparing the treatment and control groups, postoperative cardiovascular complications occurred in 25% versus 27%, intraoperative complications in 28% versus 20%, and death in 9% versus 5%, respectively. None of these differences was statistically significant as a whole or within the subgroups undergoing AR or LSP.
                These data suggest that preoperative optimization of cardiovascular function by using achievement of SvO2 above 65% as the end point does not result in any reduction of intraoperative or perioperative cardiac complications in patients undergoing PVS. Further studies with alternative assessments and manipulation of different cardiopulmonary parameters may yield additional information. The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.
                To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, beta-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).
                Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.
                Thirty-seven community hospitals in Minnesota.
                All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.
                Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.
                Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.
                Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.
                Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, beta-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients. To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI).
                Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean +/- SD increase 7.1 +/- 12.3 vs. 1.2 +/- 11.5%, P = 0.05) or by 2-D echocardiography (mean +/- SD increase 4.0 +/- 11.2 vs. -1.4 +/- 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion.
                Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI. Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction.
                Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups.
                Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group. To assess the efficacy of a multifactorial educational intervention carried out by a pharmacist in patients with heart failure (HF).
                A randomized, prospective, open clinical trial in patients admitted for HF. The patients assigned to the intervention group received information about the disease, drug therapy, diet education, and active telephone follow-up. Visits were completed at 2, 6, and 12 months. Hospital re-admissions, days of hospital stay, treatment compliance, satisfaction with the care received, and quality of life (EuroQol) were evaluated; a financial study was conducted in order to assess the possible impact of the program. The intervention was performed by the pharmacy department in coordination with the cardiology unit.
                134 patients were included, with a mean age of 75 years and a low educational level. The patients of the intervention group had a higher level of treatment compliance than the patients in the control group. At 12 months of follow-up, 32.9% fewer patients in the intervention group were admitted again vs. the control group. The mean days of hospital stay per patient in the control group were 9.6 (SD=18.5) vs. 5.9 (SD=14.1) in the intervention group. No differences were recorded in quality of life, but the intervention group had a higher score in the satisfaction scale at two months [9.0 (SD=1.3) versus 8.2 (SD=1.8) p=0.026]. Upon adjusting a Cox survival model with the ejection fraction, the patients in the intervention group had a lower risk of re-admission (Hazard ratio 0.56; 95% CI: 0.32-0.97). The financial analysis evidenced savings in hospital costs of euro 578 per patient that were favorable to the intervention group.
                Postdischarge pharmaceutical care allows for reducing the number of new admissions in patients with heart failure, the total days of hospital stay, and improves treatment compliance without increasing the costs of care. Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking.
                TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001).
                The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice. We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric-end-tidal carbon dioxide partial pressure (PCO(2)) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 +/- 7 mm of Hg vs. 17 +/- 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 +/- 15 mm of Hg vs. 79 +/- 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values.
                (c) 2006 AASLD The Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial was a multicenter, randomized, open-label trial comparing the safety and performance of 13- and 17-mm QuaDDS stents (n = 126) (Quanam Medical Corp., Santa Clara, California/Boston Scientific Corp., Natick, Massachusetts) versus uncoated control stents (n = 140) in focal, de novo coronary lesions.
                The pioneering drug-delivery QuaDDS stent used four to six acrylate polymer sleeves, each loaded with 800 microg of the paclitaxel derivative 7-hexanoyltaxol.
                Clinical end points were assessed at 1, 6, and 12 months post procedure. Quantitative coronary angiography and intravascular ultrasound were performed post procedure and at six-month follow-up.
                In the QuaDDS group, early stent thrombosis and myocardial infarction (MI) rates were significantly higher, leading to premature cessation of enrollment. For the QuaDDS group, the stent thrombosis rate increased from 3.2% to 10.3% between 1 and 12 months, associated with increased non-Q-wave MI and death rates. The angiographic restenosis rate at six months was reduced from 32.7% (control) to 7.4% (p < 0.0001). However, the primary end point was not met with six-month target vessel revascularization (TVR) rate as well as the composite major adverse cardiac event rates (cardiac death, MI, and TVR) comparable between groups.
                Despite angiographic indications of potential anti-restenotic benefit, increased rates of stent thrombosis, MI, and cardiac death associated with the QuaDDS stent show an unacceptable safety profile.
Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.