Long-term effects of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: 5-year results from the randomized-controlled BOOST trial--an echocardiographic study.

AIMS: We have recently observed that intracoronary autologous bone marrow cell (BMC)-transfer improves parameters of diastolic function in patients after acute myocardial infarction at 6 and 18 months. There is no clinical study addressing the long-term effect of BMC transfer on diastolic function. Therefore, we conducted a 5-year follow-up of the BOOST trial to evaluate a sustained benefit on echocardiographic parameters on diastolic function. METHODS AND RESULTS: After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation MI, patients were randomized to a control (n = 28) or BMC transfer group (n = 28). Echocardiography was performed at 4.5 +/- 1.5 days after PCI, at 6, 18, and 60 months. Diastolic function was determined by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (E(a)/A(a) ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall treatment effect of BMC transfer on E/A (0.25 +/- 0.10; 95% CI 0.05-0.44; P = 0.01). E/A ratio was significantly lower at 6 (Control 0.90 +/- 0.07; BMC 1.23 +/- 0.14; P = 0.03) and 18 months (Control 0.87+/-0.04; BMC 1.13 +/- 0.09; P = 0.01) in the control group, whereas E/A ratio was not different at 60 months between both groups (Control 0.90 +/- 0.06; BMC 1.05 +/- 0.07; P = 0.12). We found no overall effect of BMC transfer on E(a)/A(a) ratio (0.21 +/- 0.14; 95% CI -0.03 to 0.46; P = 0.09), DT (-12 +/- 11 ms; 95% CI -21 to 28; P = 0.75), IVRT -6 +/- 7 ms; 95% CI -9 to 19; P = 0.43), and E/E(a) ratio (0.58 +/- 0.88; 95% CI -1.18 to 2.34; P = 0.51). CONCLUSION: Intracoronary autologous BMC transfer provides an overall treatment effect on echocardiographic parameters of diastolic function in patients after AMI. However, this effect is basically related to an early improvement of parameters of diastolic function without a sustained effect on long-term follow-up.

Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial.

AIMS: We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27). METHODS AND RESULTS: Left ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 +/- 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 +/- 9.5% in the control group and by 2.5 +/- 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040). CONCLUSION: A single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.

Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study.

AIMS: Identification of risk factors for ventricular tachycardia/ventricular fibrillation (VT/VF) occurrence in patients with implantable cardioverter-defibrillators (ICD) is reasonable, because ICD patients with multiple risk factors might benefit from more aggressive anti-arrhythmic therapy for the prevention of arrhythmic events. Furthermore, in the era of prophylactic ICD therapy and limited healthcare resources, additional markers are needed for improved patient selection. METHODS AND RESULTS: Thus, in Prospective Analysis of Risk Factor for Appropriate ICD Therapy (PROFIT), we prospectively analyzed the role of ejection fraction (EF), N-terminal probrain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) class, atrial fibrillation, and QRS-duration as independent predictors for VT/VF occurrence in 250 ICD patients. Kaplan-Meier analysis showed that EF<40% (log-rank P=0.001), NT-proBNP levels higher than median (>or=405 ng/L; log-rank P=0.04), QRS-duration >or=150 ms (log-rank P=0.016), permanent atrial fibrillation (log-rank P=0.008), and higher NYHA class (log-rank P=0.029) were associated with VT/VF occurrence. By multivariate Cox regression analysis EF, QRS-duration and atrial fibrillation remained significantly associated with appropriate VT/VF therapy, whereas there was no relationship among NT-proBNP, NYHA class, and VT/VF occurrence. Stratifying patients according to the number of their independent risk factors (EF<40%, AF, QRS-width>or=150 ms) showed that patients with greater than or equal to two risk factors had a 100% 2-year risk of VT/VF occurrence, whereas patients with no or one risk factor had a 19.3 and 25% 2-year risk, respectively. CONCLUSIONS: EF<40%, permanent atrial fibrillation, and QRS>or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients. Combining all independent predictors, we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100% 2-year risk. Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy.

Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial.

BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered. METHODS AND RESULTS: After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001). CONCLUSIONS: In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.

BACKGROUND: Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aimed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction (LVEF) at 6 months' follow-up. METHODS: After successful percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction, 60 patients were randomly assigned to either a control group (n=30) that received optimum postinfarction medical treatment, or a bone-marrow-cell group (n=30) that received optimum medical treatment and intracoronary transfer of autologous bone-marrow cells 4.8 days (SD 1.3) after PCI. Primary endpoint was global left-ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up, as determined by cardiac MRI. Image analyses were done by two investigators blinded for treatment assignment. Analysis was per protocol. FINDINGS: Global LVEF at baseline (determined 3.5 days [SD 1.5] after PCI) was 51.3 (9.3%) in controls and 50.0 (10.0%) in the bone-marrow cell group (p=0.59). After 6 months, mean global LVEF had increased by 0.7 percentage points in the control group and 6.7 percentage points in the bone-marrow-cell group (p=0.0026). Transfer of bone-marrow cells enhanced left-ventricular systolic function primarily in myocardial segments adjacent to the infarcted area. Cell transfer did not increase the risk of adverse clinical events, in-stent restenosis, or proarrhythmic effects. INTERPRETATION: Intracoronary transfer of autologous bone-marrow-cells promotes improvement of left-ventricular systolic function in patients after acute myocardial infarction.

Evaluation of left ventricular diastolic function by pulsed Doppler tissue imaging in mice.

BACKGROUND: Diastolic left ventricular (LV) function is commonly characterized by transmitral flow pattern in human beings. Recently, Doppler tissue imaging (DTI) was introduced to evaluate diastolic function. The aim of our study was to validate DTI in the evaluation of diastolic function in mice. METHODS: We measured indices of diastolic function using pulsed DTI, and transmitral Doppler and LV pressure and its maximal rate of decrease (LVdP/dt(min)), before and 4 weeks after aortic banding in C57BL/6 mice. RESULTS: Peak early diastolic velocity and ratio of peak early-to-late filling velocities, both measured by DTI, were significantly reduced after banding, thereby indicating diastolic dysfunction. Diastolic dysfunction was confirmed by impaired LV dP/dt(min), decreased transmitral early filling velocity, and transmitral early-to-late filling velocity ratio using transmitral Doppler. CONCLUSION: DTI detects diastolic dysfunction caused by chronic pressure overload in mice after aortic banding. DTI is suggested to be implemented as part of routine mouse echocardiography for evaluation of LV diastolic function.