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.
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.
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.